Table of SynGAP1 Isoform α2 (UniProt Q96PV0-1) Missense Variants.

c.dna	Variant	SGM Consensus	Domain and Structure information: based on WT protein												Annotated databases						Deep learning-based pathogenicity predictions					Folding stability-based pathogenicity predictions									Sequence/structure-based pathogenicity predictions														Phase Separation			Evolutionary/physical properties				Molecular Dynamics-based analysis															DOI
			Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	PhosphoSitePlus				ClinVar			gnomAD			ESM1b		AlphaMissense			FoldX			Rosetta		Foldetta		PremPS		REVEL		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PSMutPred			PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	LTP	HTP	KL	PTM	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	IP RF	SP RF	Prediction	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.1265A>G	E422G 2D 3DClick to see structure in 3D Viewer AISynGAP1 E422G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, premPS, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are provided by FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy analyses indicate that the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a likely pathogenic effect, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta shows no definitive stability change. Overall, the majority of evidence points toward a pathogenic impact for E422G, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-11.468	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	1.13	Ambiguous	0.0	1.25	Ambiguous	1.19	Ambiguous	0.39	Likely Benign	0.488	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.01	Affected			0.2440	0.4184		0	-2	3.1	-72.06
c.470G>C	R157P 2D AIThe SynGAP1 missense variant R157P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates it is likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-11.463	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.450	Likely Benign	-3.38	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.79	Benign	0.00	Affected			0.2438	0.3438		0	-2	2.9	-59.07
c.1738G>C	G580R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a pathogenic outcome. No tool predicts a benign effect. Several methods return uncertain results—Rosetta, Foldetta (combining FoldX‑MD and Rosetta outputs), and premPS—so these do not influence the overall assessment. High‑accuracy evaluations reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-11.459	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.20	Destabilizing	0.1	1.26	Ambiguous	1.73	Ambiguous	0.81	Ambiguous	0.623	Likely Pathogenic	-7.33	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.26	Pathogenic	0.03	Affected			0.1009	0.3197		-3	-2	-4.1	99.14
c.641T>G	L214R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L214R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the evidence strongly favors a pathogenic effect for this variant, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-11.458	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.35	Ambiguous	0.6	0.92	Ambiguous	1.14	Ambiguous	1.68	Destabilizing	0.927	Likely Pathogenic	-4.98	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	5.75	Benign	0.00	Affected			0.1335	0.0772		-3	-2	-8.3	43.03
c.1337A>G	E446G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E446G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM. The majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-11.457	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous	2.62	Destabilizing	0.7	1.63	Ambiguous	2.13	Destabilizing	0.83	Ambiguous	0.510	Likely Pathogenic	-6.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.24	Benign	0.00	Affected			0.2665	0.5202		0	-2	3.1	-72.06
c.1909T>C	S637P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S637P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls arise from FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments give a pathogenic signal: the SGM Consensus predicts likely pathogenic, Foldetta predicts destabilizing pathogenic effects, whereas AlphaMissense‑Optimized remains uncertain. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-11.455	Likely Pathogenic	0.793	Likely Pathogenic	Ambiguous	6.73	Destabilizing	0.1	6.36	Destabilizing	6.55	Destabilizing	0.44	Likely Benign	0.192	Likely Benign	-3.12	Deleterious	0.946	Possibly Damaging	0.360	Benign	3.36	Benign	0.03	Affected			0.2374	0.4094		1	-1	-0.8	10.04
c.1067G>A	R356H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R356H is recorded in ClinVar as benign (ClinVar ID 2984966.0) and is present in the gnomAD database (6‑33437972‑G‑A). Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, with the SGM‑Consensus also labeling it likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions support a pathogenic impact, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250					Likely Benign		1	6-33437972-G-A	9	5.66e-6	-11.453	Likely Pathogenic	0.614	Likely Pathogenic	Likely Benign	0.59	Ambiguous	0.1	-0.27	Likely Benign	0.16	Likely Benign	1.17	Destabilizing	0.314	Likely Benign	-4.43	Deleterious	0.999	Probably Damaging	0.987	Probably Damaging	1.70	Pathogenic	0.01	Affected	3.39	22	0.3493	0.2206		0	2	1.3	-19.05
c.1627C>A	L543M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L543M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and PROVEAN, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Rosetta. Predictions that are uncertain (FoldX, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments give AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of available tools predict a deleterious effect, indicating that the variant is most likely pathogenic. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000											-11.452	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.68	Ambiguous	0.2	2.53	Destabilizing	1.61	Ambiguous	0.99	Ambiguous	0.382	Likely Benign	-1.99	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	1.93	Pathogenic	0.01	Affected			0.0788	0.2172		4	2	-1.9	18.03
c.1249T>C	Y417H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y417H is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for Y417H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.346865	Uncertain	0.958	0.250	0.000											-11.447	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.22	Destabilizing	0.1	2.80	Destabilizing	3.01	Destabilizing	1.54	Destabilizing	0.513	Likely Pathogenic	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.97	Benign	0.00	Affected			0.2596	0.0668		0	2	-1.9	-26.03
c.2048T>G	I683S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. No prediction or folding stability result is missing or inconclusive; all available evidence points to a deleterious effect. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-11.443	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	2.53	Destabilizing	0.2	1.94	Ambiguous	2.24	Destabilizing	1.35	Destabilizing	0.552	Likely Pathogenic	-5.88	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.29	Benign	0.05	Affected			0.1936	0.1320		-1	-2	-5.3	-26.08
c.2074C>G	L692V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as pathogenic, and Foldetta also predicts pathogenic. No predictions are missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-11.441	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	3.29	Destabilizing	0.1	2.91	Destabilizing	3.10	Destabilizing	1.57	Destabilizing	0.286	Likely Benign	-2.99	Deleterious	0.978	Probably Damaging	0.606	Possibly Damaging	3.12	Benign	0.01	Affected			0.1395	0.2460		2	1	0.4	-14.03
c.3163G>T	G1055W 2D AIThe SynGAP1 missense variant G1055W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.982235	Disordered	0.872113	Binding	0.379	0.935	0.875											-11.436	Likely Pathogenic	0.317	Likely Benign	Likely Benign										0.367	Likely Benign	-0.77	Neutral	0.997	Probably Damaging	0.946	Probably Damaging	3.28	Benign	0.01	Affected			0.0899	0.4246		-7	-2	-0.5	129.16
c.1523A>C	D508A 2D 3DClick to see structure in 3D Viewer AISynGAP1 D508A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give a split result: AlphaMissense‑Optimized predicts benign, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain. No prediction or stability result is missing; all available outputs are considered. Overall, the predictions are evenly divided between benign and pathogenic, with no clear consensus. Therefore, the variant is inconclusive; it is not contradictory to the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-11.434	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	-0.18	Likely Benign	0.2	1.84	Ambiguous	0.83	Ambiguous	0.09	Likely Benign	0.339	Likely Benign	-7.37	Deleterious	0.988	Probably Damaging	0.762	Possibly Damaging	3.37	Benign	0.06	Tolerated			0.3758	0.4241		0	-2	5.3	-44.01
c.1243G>A	E415K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E415K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus shows AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall balance of predictions—particularly the two high‑accuracy pathogenic calls versus one benign—the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-11.433	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.3	-0.13	Likely Benign	-0.10	Likely Benign	0.46	Likely Benign	0.326	Likely Benign	-3.69	Deleterious	0.998	Probably Damaging	0.975	Probably Damaging	3.22	Benign	0.03	Affected			0.2174	0.3860		0	1	-0.4	-0.94
c.3734A>C	E1245A 2D AIThe SynGAP1 missense variant E1245A is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL is the sole tool that predicts a benign effect, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise indicates a likely pathogenic effect. Foldetta results are not available for this variant. Overall, the consensus of the available predictions indicates that E1245A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.433	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic										0.311	Likely Benign	-4.85	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.2555	0.5721		0	-1	5.3	-58.04
c.445A>C	K149Q 2D AIThe SynGAP1 missense variant K149Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-11.430	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.99	Neutral	0.535	Possibly Damaging	0.310	Benign	3.61	Benign	0.00	Affected			0.5243	0.1454	Weaken	1	1	0.4	-0.04
c.1387G>A	D463N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Predictions that are uncertain (Foldetta, AlphaMissense‑Optimized, Rosetta) are treated as unavailable and do not influence the overall assessment. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta is uncertain. Overall, the majority of available predictions lean toward a benign effect, and this conclusion does not contradict any ClinVar status (none reported). Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-11.428	Likely Pathogenic	0.812	Likely Pathogenic	Ambiguous	0.10	Likely Benign	0.1	1.19	Ambiguous	0.65	Ambiguous	0.40	Likely Benign	0.217	Likely Benign	-4.37	Deleterious	0.880	Possibly Damaging	0.430	Benign	3.33	Benign	0.10	Tolerated			0.1152	0.5531		2	1	0.0	-0.98
c.893C>G	P298R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P298R has no ClinVar entry and is not reported in gnomAD. Computational predictors fall into two consensus groups: benign predictions come from REVEL, FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported only by Foldetta and premPS. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta reports an uncertain stability change. Overall, the majority of evidence points toward a pathogenic effect, and this assessment is not contradicted by ClinVar, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500											-11.427	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	0.45	Likely Benign	0.0	2.08	Destabilizing	1.27	Ambiguous	0.61	Ambiguous	0.280	Likely Benign	-1.83	Neutral	0.997	Probably Damaging	0.952	Probably Damaging	2.03	Pathogenic	0.09	Tolerated			0.1299	0.3872		0	-2	-2.9	59.07
c.782A>C	D261A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D261A missense variant is not reported in ClinVar (status: None) and has no entries in gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, while the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Given the preponderance of pathogenic predictions and the lack of conflicting evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-11.426	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	1.70	Ambiguous	0.3	1.46	Ambiguous	1.58	Ambiguous	0.04	Likely Benign	0.839	Likely Pathogenic	-4.59	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	5.80	Benign	0.04	Affected			0.2785	0.4577		0	-2	5.3	-44.01
c.802A>T	I268F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; only Rosetta and Foldetta are uncertain. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) remains uncertain. Overall, the consensus of available predictions strongly supports a pathogenic classification for I268F, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-11.426	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.7	0.59	Ambiguous	1.72	Ambiguous	1.00	Destabilizing	0.685	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.0427	0.2158		1	0	-1.7	34.02
c.2079T>A	H693Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, while the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented predictors and the high‑accuracy consensus indicates that H693Q is most likely pathogenic, a conclusion that aligns with the lack of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-11.425	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	0.78	Ambiguous	0.85	Ambiguous	1.27	Destabilizing	0.386	Likely Benign	-7.97	Deleterious	1.000	Probably Damaging	0.921	Probably Damaging	3.14	Benign	0.01	Affected			0.1274	0.2955		3	0	-0.3	-9.01
c.2079T>G	H693Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, while the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented predictors and the high‑accuracy consensus indicates that H693Q is most likely pathogenic, a conclusion that aligns with the lack of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-11.425	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	0.78	Ambiguous	0.85	Ambiguous	1.27	Destabilizing	0.386	Likely Benign	-7.97	Deleterious	1.000	Probably Damaging	0.921	Probably Damaging	3.14	Benign	0.01	Affected			0.1274	0.2955		3	0	-0.3	-9.01
c.1926G>C	K642N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K642N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. With two of the three high‑accuracy tools supporting pathogenicity and an overall balance of predictions, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.423	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.05	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.273	Likely Benign	-4.88	Deleterious	0.958	Probably Damaging	0.392	Benign	2.88	Benign	0.00	Affected			0.3553	0.1590		1	0	0.4	-14.07
c.1926G>T	K642N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K642N is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar (benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, seven tools favor pathogenicity versus six favoring benign, and the high‑accuracy predictions are mixed. Thus, the variant is most likely pathogenic based on the preponderance of evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.423	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.05	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.274	Likely Benign	-4.88	Deleterious	0.958	Probably Damaging	0.392	Benign	2.88	Benign	0.00	Affected			0.3553	0.1590		1	0	0.4	-14.07
c.937G>C	E313Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 E313Q is listed in ClinVar with an Uncertain significance status and is not reported in gnomAD. Prediction tools that classify the variant as benign include FoldX, Foldetta, premPS, PROVEAN, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized indicates a benign effect, Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign stability, whereas the SGM‑Consensus remains pathogenic. Overall, the balance of evidence leans toward pathogenicity, and this assessment does not contradict the ClinVar designation of Uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125					Uncertain		1				-11.420	Likely Pathogenic	0.629	Likely Pathogenic	Likely Benign	0.19	Likely Benign	0.1	0.55	Ambiguous	0.37	Likely Benign	0.50	Likely Benign	0.505	Likely Pathogenic	-2.42	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.88	Pathogenic	0.05	Affected			0.1523	0.7396		2	2	0.0	-0.98
c.1618C>A	Q540K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q540K is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (10 pathogenic vs. 5 benign) indicate a likely pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000											-11.418	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	-0.37	Likely Benign	0.0	-0.03	Likely Benign	-0.20	Likely Benign	0.76	Ambiguous	0.808	Likely Pathogenic	-3.98	Deleterious	0.985	Probably Damaging	0.965	Probably Damaging	-1.31	Pathogenic	0.06	Tolerated			0.1508	0.2472		1	1	-0.4	0.04
c.2053T>G	L685V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability methods provide definitive evidence. Overall, the preponderance of pathogenic predictions, including the SGM Consensus, suggests that the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-11.418	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.87	Ambiguous	0.0	1.15	Ambiguous	1.51	Ambiguous	0.97	Ambiguous	0.214	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.33	Benign	0.02	Affected			0.1414	0.3010		2	1	0.4	-14.03
c.3806T>A	V1269E 2D AIThe SynGAP1 missense change V1269E is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that flag the variant as benign include only REVEL, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classify it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Pathogenic” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125					Uncertain		1				-11.418	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.403	Likely Benign	-5.05	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.09	Pathogenic	0.00	Affected	3.77	5	0.0899	0.1557		-2	-2	-7.7	29.98
c.835C>T	R279W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R279W is listed in ClinVar with an uncertain significance (ClinVar ID 1204186.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining pathogenic‑predicating tools—FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a deleterious impact. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R279W, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125					Uncertain		1				-11.417	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	2.00	Destabilizing	0.8	1.47	Ambiguous	1.74	Ambiguous	0.80	Ambiguous	0.485	Likely Benign	-6.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.88	Pathogenic	0.00	Affected	3.39	18	0.1200	0.2519		2	-3	3.6	30.03	270.0	38.3	0.1	0.0	0.3	0.0								Uncertain	The guanidinium group of Arg279, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), can form hydrogen bond with the backbone carbonyl groups of nearby loop residues (e.g., Ser296, Ser331, and As332) and form salt bridges with the carboxylate groups of Asp330 and Asp332. In the WT simulations, Arg279 sporadically forms a salt bridge even with the carboxylate group of Glu613, loosely connecting the C2 domain and GAP domain. Meanwhile, the indole ring of the Trp279 side chain is unable to hydrogen bond with the loop residues in the variant simulations. The lack of hydrogen bond or salt bridge formation with the loop residues could be significant, as Arg279 and the loops face the polar head group region of the membrane. Thus, although Trp279 could interact with the membrane surface as a “lipid anchor,” any changes to the wider loop dynamics could still adversely affect the formation of a stable SynGAP-membrane association. However, no definite conclusions on the effect of the residue swap on the SynGAP-membrane association can be drawn from solvent-only simulations.
c.1878T>G	I626M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I626M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and premPS give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-11.407	Likely Pathogenic	0.618	Likely Pathogenic	Likely Benign	0.72	Ambiguous	0.1	1.78	Ambiguous	1.25	Ambiguous	0.92	Ambiguous	0.405	Likely Benign	-2.76	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.06	Benign	0.02	Affected			0.0661	0.1959		2	1	-2.6	18.03
c.2128A>G	K710E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K710E missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-11.405	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.0	0.94	Ambiguous	0.75	Ambiguous	0.39	Likely Benign	0.178	Likely Benign	-3.53	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.45	Benign	0.08	Tolerated			0.2655	0.0789		0	1	0.4	0.94
c.1252A>C	K418Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K418Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-11.404	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.17	Likely Benign	0.14	Likely Benign	0.30	Likely Benign	0.263	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.55	Benign	0.13	Tolerated			0.4105	0.0696		1	1	0.4	-0.04
c.1459A>C	N487H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N487H has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) predict a pathogenic or likely pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from these tools contradicts the lack of ClinVar annotation. Overall, the preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-11.403	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	1.15	Ambiguous	0.1	0.84	Ambiguous	1.00	Ambiguous	0.72	Ambiguous	0.548	Likely Pathogenic	-4.97	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.00	Affected			0.1123	0.3411		2	1	0.3	23.04
c.953C>A	P318Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity. Only FoldX, Rosetta, and Foldetta provide uncertain results and are therefore not considered evidence for benign impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Consequently, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000											-11.403	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.64	Ambiguous	0.2	1.29	Ambiguous	1.47	Ambiguous	1.18	Destabilizing	0.638	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.83	Pathogenic	0.01	Affected			0.1467	0.4731		0	-1	-1.9	31.01
c.1508A>G	Q503R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q503R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include FoldX, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. The high‑accuracy methods give a benign result for AlphaMissense‑Optimized, a pathogenic result for the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and a benign result for Foldetta (combining FoldX‑MD and Rosetta). Overall, the majority of tools and the high‑accuracy methods lean toward a benign effect. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.322935	Uncertain	0.848	0.168	0.000											-11.396	Likely Pathogenic	0.232	Likely Benign	Likely Benign	-0.40	Likely Benign	0.3	0.60	Ambiguous	0.10	Likely Benign	0.50	Likely Benign	0.640	Likely Pathogenic	-3.34	Deleterious	0.577	Possibly Damaging	0.395	Benign	-1.42	Pathogenic	0.06	Tolerated			0.1426	0.0963		1	1	-1.0	28.06
c.2039A>G	E680G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E680G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools lean toward a pathogenic effect, with high‑accuracy methods split but tipping toward pathogenicity. The variant’s status in ClinVar is unknown, so there is no contradiction between the predictions and existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-11.396	Likely Pathogenic	0.743	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.2	0.11	Likely Benign	0.39	Likely Benign	0.44	Likely Benign	0.411	Likely Benign	-5.48	Deleterious	0.998	Probably Damaging	0.739	Possibly Damaging	3.47	Benign	0.01	Affected			0.2708	0.6228		0	-2	3.1	-72.06
c.2035T>C	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for F679L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.506	Likely Pathogenic	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2037T>A	F679L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F679L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, FATHMM, and Foldetta, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. The majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.287	Likely Benign	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2037T>G	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and premPS are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.287	Likely Benign	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.1733A>T	E578V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E578V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors cluster into two groups: benign predictions come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: FoldX and AlphaMissense‑Optimized. High‑accuracy assessments further show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence favors a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-11.393	Likely Pathogenic	0.881	Likely Pathogenic	Ambiguous	0.72	Ambiguous	0.1	0.02	Likely Benign	0.37	Likely Benign	0.12	Likely Benign	0.607	Likely Pathogenic	-3.74	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	-1.43	Pathogenic	0.13	Tolerated			0.0575	0.5703		-2	-2	7.7	-29.98
c.1708G>A	A570T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570T is not reported in ClinVar and is absent from gnomAD. Prediction tools that provide a definitive call all indicate a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. No tool reports a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are uncertain and therefore do not influence the overall assessment. High‑accuracy methods specifically show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Taken together, the majority of conclusive predictions support a pathogenic effect. Consequently, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000											-11.390	Likely Pathogenic	0.801	Likely Pathogenic	Ambiguous	1.45	Ambiguous	0.3	1.67	Ambiguous	1.56	Ambiguous	0.86	Ambiguous	0.568	Likely Pathogenic	-3.28	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	-1.26	Pathogenic	0.05	Affected			0.1345	0.3874		1	0	-2.5	30.03
c.1538T>G	F513C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513C is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also labels it pathogenic. Based on the uniform predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-11.389	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	3.92	Destabilizing	0.3	4.20	Destabilizing	4.06	Destabilizing	1.64	Destabilizing	0.919	Likely Pathogenic	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.40	Pathogenic	0.03	Affected			0.2384	0.0783		-4	-2	-0.3	-44.04
c.2065C>G	L689V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) and the SGM Consensus (Likely Pathogenic) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM Consensus is Likely Pathogenic; Foldetta predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for L689V. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-11.387	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	2.98	Destabilizing	0.1	2.25	Destabilizing	2.62	Destabilizing	1.32	Destabilizing	0.234	Likely Benign	-2.97	Deleterious	0.926	Possibly Damaging	0.481	Possibly Damaging	3.27	Benign	0.00	Affected			0.1393	0.3189		2	1	0.4	-14.03
c.1847A>C	D616A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616A missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), Rosetta, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as benign, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-11.386	Likely Pathogenic	0.664	Likely Pathogenic	Likely Benign	1.76	Ambiguous	0.2	2.07	Destabilizing	1.92	Ambiguous	0.41	Likely Benign	0.126	Likely Benign	-6.13	Deleterious	0.539	Possibly Damaging	0.122	Benign	3.32	Benign	0.10	Tolerated			0.3543	0.4207		0	-2	5.3	-44.01
c.736C>A	L246M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L246M has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include PROVEAN and FATHMM, while a majority (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are uncertain. High‑accuracy methods are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Thus no high‑accuracy tool provides a definitive verdict. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any ClinVar status because no ClinVar record exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.472492	Structured	0.302312	Uncertain	0.859	0.364	0.000											-11.386	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.65	Ambiguous	0.2	0.76	Ambiguous	0.71	Ambiguous	0.87	Ambiguous	0.661	Likely Pathogenic	-1.79	Neutral	0.997	Probably Damaging	0.916	Probably Damaging	4.72	Benign	0.01	Affected			0.0710	0.3511		4	2	-1.9	18.03
c.1798C>G	P600A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P600A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from Rosetta and premPS, while the remaining 11 tools (REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM Consensus) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports an uncertain result. Taken together, the overwhelming majority of evidence indicates that P600A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.162960	Uncertain	0.947	0.147	0.000											-11.385	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.0	-3.30	Stabilizing	-0.57	Ambiguous	0.39	Likely Benign	0.581	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.38	Pathogenic	0.03	Affected			0.3692	0.4132		1	-1	3.4	-26.04
c.1513T>C	Y505H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505H is listed in ClinVar as Pathogenic (ClinVar ID 3064218.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy consensus methods reinforce this view: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also Pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among predictive tools, the variant is most likely pathogenic, consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.292227	Uncertain	0.909	0.188	0.000					Likely Pathogenic		1				-11.383	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	2.91	Destabilizing	0.1	2.88	Destabilizing	2.90	Destabilizing	1.60	Destabilizing	0.646	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.64	Benign	0.00	Affected	3.37	35	0.2148	0.0612		2	0	-1.9	-26.03
c.3757G>C	A1253P 2D AIThe SynGAP1 missense variant A1253P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while AlphaMissense‑Default also predicts pathogenic; however, the majority of tools (five benign vs. four pathogenic) lean toward a benign classification. Thus, based on the current predictions, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.661982	Disordered	0.391377	Uncertain	0.881	0.550	0.750											-11.381	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.062	Likely Benign	-0.63	Neutral	0.568	Possibly Damaging	0.352	Benign	2.74	Benign	0.26	Tolerated			0.1565	0.3514		1	-1	-3.4	26.04
c.2068T>A	S690T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, FATHMM, and polyPhen‑2 HumVar, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive (FoldX, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-11.380	Likely Pathogenic	0.845	Likely Pathogenic	Ambiguous	0.99	Ambiguous	0.2	-0.21	Likely Benign	0.39	Likely Benign	0.67	Ambiguous	0.311	Likely Benign	-2.84	Deleterious	0.943	Possibly Damaging	0.267	Benign	3.37	Benign	0.01	Affected			0.1059	0.4674		1	1	0.1	14.03
c.1478C>G	A493G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A493G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus all predict pathogenicity, while only AlphaMissense‑Optimized predicts a benign outcome. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore not considered evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains pathogenic; Foldetta likewise yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic effect for A493G, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000											-11.379	Likely Pathogenic	0.571	Likely Pathogenic	Likely Benign	1.85	Ambiguous	0.0	1.63	Ambiguous	1.74	Ambiguous	1.40	Destabilizing	0.764	Likely Pathogenic	-3.54	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.40	Pathogenic	0.02	Affected			0.1673	0.2228		1	0	-2.2	-14.03
c.2134G>T	G712C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G712C is catalogued in gnomAD (6‑33441599‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000								6-33441599-G-T	1	6.20e-7	-11.376	Likely Pathogenic	0.829	Likely Pathogenic	Ambiguous	2.54	Destabilizing	0.0	5.72	Destabilizing	4.13	Destabilizing	0.56	Ambiguous	0.516	Likely Pathogenic	-7.75	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.31	Benign	0.00	Affected	3.50	9	0.1513	0.3947		-3	-3	2.9	46.09
c.1681T>G	F561V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. All available evidence points to a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-11.371	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.1	2.58	Destabilizing	2.85	Destabilizing	1.48	Destabilizing	0.827	Likely Pathogenic	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.04	Affected			0.1985	0.1575		-1	-1	1.4	-48.04
c.1250A>T	Y417F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y417F variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from AlphaMissense‑Optimized and premPS. High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta) as Benign, and AlphaMissense‑Optimized as Uncertain. Overall, the majority of tools and the SGM‑Consensus score suggest a pathogenic effect, while Foldetta indicates a benign effect; the variant’s status is not contradicted by ClinVar (no entry). Thus, based on the available predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.346865	Uncertain	0.958	0.250	0.000											-11.368	Likely Pathogenic	0.852	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	-0.09	Likely Benign	0.19	Likely Benign	0.97	Ambiguous	0.367	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.03	Benign	0.06	Tolerated			0.2617	0.3098		7	3	4.1	-16.00
c.1996G>A	E666K 2D AIThe SynGAP1 missense variant E666K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-11.367	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.20	Likely Benign	0.6	0.30	Likely Benign	0.25	Likely Benign	0.43	Likely Benign	0.401	Likely Benign	-3.26	Deleterious	0.992	Probably Damaging	0.717	Possibly Damaging	3.46	Benign	0.05	Affected			0.2953	0.5300		0	1	-0.4	-0.94
c.1382C>G	A461G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461G has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into three groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; the remaining tools (FoldX, premPS, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, with no ClinVar record to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-11.360	Likely Pathogenic	0.556	Ambiguous	Likely Benign	1.46	Ambiguous	0.1	2.06	Destabilizing	1.76	Ambiguous	0.83	Ambiguous	0.276	Likely Benign	-3.79	Deleterious	0.991	Probably Damaging	0.628	Possibly Damaging	3.32	Benign	0.00	Affected			0.1988	0.3317		1	0	-2.2	-14.03
c.998A>C	K333T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K333T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, and SIFT, whereas a larger set—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score—predict a pathogenic impact. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) reports a benign effect. Overall, the majority of evidence points to a pathogenic effect for K333T, and this conclusion does not conflict with any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-11.358	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.0	-0.15	Likely Benign	0.18	Likely Benign	0.46	Likely Benign	0.506	Likely Pathogenic	-4.82	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.96	Pathogenic	0.08	Tolerated			0.1839	0.3354		0	-1	3.2	-27.07
c.1504G>A	G502S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G502S is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated predictors—SGM Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently classify the variant as pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts a benign outcome, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000											-11.357	Likely Pathogenic	0.616	Likely Pathogenic	Likely Benign	2.09	Destabilizing	0.6	0.71	Ambiguous	1.40	Ambiguous	0.96	Ambiguous	0.839	Likely Pathogenic	-5.74	Deleterious	0.975	Probably Damaging	0.862	Possibly Damaging	-1.64	Pathogenic	0.01	Affected			0.2429	0.3217		1	0	-0.4	30.03
c.1435C>T	R479W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R479W is not reported in ClinVar and is present in gnomAD (ID 6‑33438467‑C‑T). Functional prediction tools show a split opinion: benign calls come from REVEL, premPS, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic; Foldetta remains inconclusive. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000								6-33438467-C-T	6	3.72e-6	-11.356	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.60	Ambiguous	0.1	0.72	Ambiguous	0.66	Ambiguous	0.42	Likely Benign	0.249	Likely Benign	-4.75	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.35	Benign	0.02	Affected	3.39	32	0.1046	0.2933		-3	2	3.6	30.03
c.1817G>A	S606N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S606N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Because the majority of individual predictors lean toward pathogenic and the SGM‑Consensus, a high‑confidence consensus, also indicates pathogenicity, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-11.352	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous	0.11	Likely Benign	0.1	0.20	Likely Benign	0.16	Likely Benign	0.76	Ambiguous	0.136	Likely Benign	-2.99	Deleterious	0.920	Possibly Damaging	0.955	Probably Damaging	3.37	Benign	0.10	Tolerated			0.1137	0.3218		1	1	-2.7	27.03
c.2150T>G	L717R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717R is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the majority‑vote SGM Consensus) predict pathogenicity; FoldX is uncertain. High‑accuracy methods reinforce a pathogenic verdict: AlphaMissense‑Optimized scores it as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. No prediction is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-11.352	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.1	3.78	Destabilizing	2.72	Destabilizing	1.57	Destabilizing	0.353	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.28	Benign	0.00	Affected			0.1169	0.0558		-3	-2	-8.3	43.03
c.704C>G	S235C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S235C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FATHMM and Rosetta, whereas a majority of tools (REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Results from high‑accuracy methods are mixed: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta is uncertain. Because the uncertain predictions are treated as unavailable, the overall evidence still favors pathogenicity. Thus, the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.250310	Structured	0.319150	Uncertain	0.743	0.331	0.000											-11.350	Likely Pathogenic	0.800	Likely Pathogenic	Ambiguous	1.74	Ambiguous	0.1	0.42	Likely Benign	1.08	Ambiguous	0.76	Ambiguous	0.878	Likely Pathogenic	-4.24	Deleterious	0.977	Probably Damaging	0.620	Possibly Damaging	5.45	Benign	0.00	Affected			0.1284	0.6015		0	-1	3.3	16.06
c.641T>C	L214P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L214P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, while the remaining 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, and the consensus of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the overwhelming agreement among predictive algorithms, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-11.348	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.38	Destabilizing	1.3	7.51	Destabilizing	5.45	Destabilizing	1.30	Destabilizing	0.930	Likely Pathogenic	-5.98	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	5.76	Benign	0.00	Affected			0.3448	0.1553		-3	-3	-5.4	-16.04
c.1612G>A	E538K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E538K has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment indicates that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) supports a pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the majority of tools lean toward a benign effect, but the consensus of high‑accuracy predictors and several individual pathogenic scores suggest uncertainty. The variant is most likely benign based on the bulk of evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-11.345	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.16	Likely Benign	-0.10	Likely Benign	-0.22	Likely Benign	0.215	Likely Benign	-2.97	Deleterious	0.848	Possibly Damaging	0.294	Benign	3.46	Benign	0.16	Tolerated			0.2257	0.3818		0	1	-0.4	-0.94
c.3784A>T	I1262F 2D AIThe SynGAP1 missense variant I1262F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-11.343	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.515	Likely Pathogenic	-3.32	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0532	0.2731		1	0	-1.7	34.02
c.1462A>G	T488A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T488A is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the majority of tools (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) predict pathogenicity; Rosetta and premPS are uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence indicates that T488A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-11.341	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.2	1.99	Ambiguous	2.06	Destabilizing	0.57	Ambiguous	0.497	Likely Benign	-4.64	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.24	Benign	0.01	Affected			0.2871	0.2872		1	0	2.5	-30.03
c.3767A>G	D1256G 2D AIThe SynGAP1 missense variant D1256G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the benign‑predicting REVEL score, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenicity. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect for D1256G. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-11.341	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.457	Likely Benign	-5.45	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.00	Affected			0.2886	0.5040		1	-1	3.1	-58.04
c.2039A>C	E680A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E680A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of predictions lean toward pathogenicity, but the conflicting high‑accuracy results leave the classification uncertain. The variant is most likely pathogenic based on the prevailing evidence, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-11.338	Likely Pathogenic	0.819	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.2	0.59	Ambiguous	0.47	Likely Benign	0.30	Likely Benign	0.444	Likely Benign	-5.22	Deleterious	0.935	Possibly Damaging	0.490	Possibly Damaging	3.47	Benign	0.09	Tolerated			0.3931	0.6989		0	-1	5.3	-58.04
c.1765A>C	I589L 2D AIThe SynGAP1 missense variant I589L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only PROVEAN, whereas the remaining tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized and Foldetta are inconclusive and therefore not considered evidence. Taken together, the preponderance of evidence points to a pathogenic effect for I589L. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018415	Structured	0.084536	Uncertain	0.927	0.214	0.000											-11.337	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous	0.95	Ambiguous	1.1	1.44	Ambiguous	1.20	Ambiguous	0.95	Ambiguous	0.728	Likely Pathogenic	-1.99	Neutral	0.955	Possibly Damaging	0.985	Probably Damaging	-1.76	Pathogenic	0.02	Affected			0.1243	0.3430		2	2	-0.7	0.00
c.925G>A	G309S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G309S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include REVEL and SIFT, whereas a majority of other in silico predictors (AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SGM‑Consensus, and FoldX) predict it to be pathogenic. Tools with uncertain outcomes (Foldetta, Rosetta, premPS) provide no definitive evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that G309S is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.338439	Uncertain	0.882	0.342	0.125											-11.335	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	2.82	Destabilizing	0.5	0.73	Ambiguous	1.78	Ambiguous	0.72	Ambiguous	0.487	Likely Benign	-5.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.73	Pathogenic	0.07	Tolerated			0.2828	0.5591		1	0	-0.4	30.03
c.1028T>G	V343G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the preponderance of evidence indicates that V343G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250											-11.332	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	2.49	Destabilizing	0.1	4.40	Destabilizing	3.45	Destabilizing	1.68	Destabilizing	0.421	Likely Benign	-5.84	Deleterious	0.898	Possibly Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.00	Affected			0.1982	0.3341		-1	-3	-4.6	-42.08
c.891G>C	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.891G>T	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, K297N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.1531G>A	G511R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G511R is listed in ClinVar as Pathogenic (ClinVar ID 1774641.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Stability calculations from FoldX and Rosetta are uncertain, and premPS is unavailable. Overall, the majority of evidence points to a pathogenic impact, aligning with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000					Likely Pathogenic		1				-11.327	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.94	Ambiguous	0.3	1.32	Ambiguous	1.63	Ambiguous	0.94	Ambiguous	0.416	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.26	Benign	0.06	Tolerated	3.37	35	0.1307	0.4104		-3	-2	-4.1	99.14	279.4	-159.9	0.0	0.0	0.7	0.1			X				X	Potentially Pathogenic	Gly511 is located in an α-helix (res. Gly502-Tyr518), facing hydrophobic residues in an inter-helix space (e.g., Leu610, Ile514) in the WT simulations. In contrast, in the variant simulations, the bulkier and positively charged guanidinium side chain of Arg511 forms a salt bridge with the carboxylate group of Glu217 or hydrogen bonds with the backbone carbonyl group of Leu610. Although the residue swap introduces a third positively charged residue in close vicinity (Arg511, Lys507, Arg515), the protein structure seems to remain stable in the variant simulations. Importantly, according to ClinVar, the residue swap alters the last nucleotide of an exon and is predicted to destroy the splice donor site, resulting in aberrant splicing and pathogenic status.	10.1016/j.ajhg.2020.11.011
c.1531G>C	G511R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511R is listed in ClinVar (ID 452818.0) as Pathogenic and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain, which is treated as unavailable evidence. Overall, the majority of available predictions support a pathogenic impact, aligning with the ClinVar classification. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000					Pathogenic		1				-11.327	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.94	Ambiguous	0.3	1.32	Ambiguous	1.63	Ambiguous	0.94	Ambiguous	0.415	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.26	Benign	0.06	Tolerated	3.37	35	0.1307	0.4104		-3	-2	-4.1	99.14	279.4	-159.9	0.0	0.0	0.7	0.1			X				X	Potentially Pathogenic	Gly511 is located in an α-helix (res. Gly502-Tyr518), facing hydrophobic residues in an inter-helix space (e.g., Leu610, Ile514) in the WT simulations. In contrast, in the variant simulations, the bulkier and positively charged guanidinium side chain of Arg511 forms a salt bridge with the carboxylate group of Glu217 or hydrogen bonds with the backbone carbonyl group of Leu610. Although the residue swap introduces a third positively charged residue in close vicinity (Arg511, Lys507, Arg515), the protein structure seems to remain stable in the variant simulations. Importantly, according to ClinVar, the residue swap alters the last nucleotide of an exon and is predicted to destroy the splice donor site, resulting in aberrant splicing and pathogenic status.	10.1016/j.ajhg.2020.11.011
c.1213C>A	R405S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM‑Consensus itself is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts Pathogenic. Taken together, the overwhelming majority of evidence indicates that R405S is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.326	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.66	Destabilizing	0.5	2.08	Destabilizing	2.37	Destabilizing	1.22	Destabilizing	0.405	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.67	Benign	0.05	Affected			0.2829	0.4646		0	-1	3.7	-69.11
c.1367A>G	Q456R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, whereas Foldetta (a folding‑stability method combining FoldX‑MD and Rosetta outputs) predicts benign. No evidence from the data contradicts ClinVar status, which is currently unclassified. Based on the available predictions, the variant is most likely benign, though the evidence is conflicting and does not conflict with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-11.326	Likely Pathogenic	0.801	Likely Pathogenic	Ambiguous	0.21	Likely Benign	0.1	0.12	Likely Benign	0.17	Likely Benign	0.33	Likely Benign	0.295	Likely Benign	-3.69	Deleterious	0.980	Probably Damaging	0.943	Probably Damaging	3.37	Benign	0.20	Tolerated			0.1241	0.1124		1	1	-1.0	28.06
c.1783C>A	L595M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L595M is not reported in ClinVar (ClinVar ID: None) and has no entries in gnomAD (gnomAD ID: None). Functional prediction tools show a split consensus: benign predictions come from REVEL, FoldX, Rosetta, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect on protein stability. No prediction or folding result is missing; all available outputs are reported. Based on the balanced distribution of benign and pathogenic calls, the variant is most likely benign, but the evidence is conflicting and does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000											-11.325	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.0	0.41	Likely Benign	0.37	Likely Benign	0.90	Ambiguous	0.387	Likely Benign	-1.99	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.74	Benign	0.02	Affected			0.0930	0.3140		4	2	-1.9	18.03
c.1883A>G	K628R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K628R is reported in gnomAD (variant ID 6‑33440935‑A‑G) but has no ClinVar entry. Functional prediction tools show a split assessment: benign calls come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized, whereas pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Two tools remain inconclusive (premPS and AlphaMissense‑Default). The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a likely pathogenic verdict, while the high‑accuracy AlphaMissense‑Optimized predicts benign. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the majority of evidence leans toward pathogenicity, and this conclusion does not conflict with ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000								6-33440935-A-G	1	6.20e-7	-11.324	Likely Pathogenic	0.476	Ambiguous	Likely Benign	0.22	Likely Benign	0.1	-0.11	Likely Benign	0.06	Likely Benign	0.94	Ambiguous	0.592	Likely Pathogenic	-2.99	Deleterious	0.996	Probably Damaging	0.990	Probably Damaging	2.49	Pathogenic	0.00	Affected	3.37	34	0.3873	0.0873		2	3	-0.6	28.01
c.2138C>T	P713L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-11.323	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous	0.18	Likely Benign	0.1	-0.03	Likely Benign	0.08	Likely Benign	0.55	Ambiguous	0.324	Likely Benign	-8.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.34	Benign	0.00	Affected			0.1993	0.5261		-3	-3	5.4	16.04
c.3733G>C	E1245Q 2D AIThe SynGAP1 missense change E1245Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3 pathogenic vs. 1 benign). High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is not available. Consequently, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.323	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous										0.210	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.0819	0.5952		2	2	0.0	-0.98
c.3154G>T	G1052W 2D AIThe SynGAP1 missense variant G1052W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-11.322	Likely Pathogenic	0.309	Likely Benign	Likely Benign										0.457	Likely Benign	-0.90	Neutral	0.997	Probably Damaging	0.946	Probably Damaging	3.90	Benign	0.02	Affected			0.0872	0.4046		-7	-2	-0.5	129.16
c.1873C>G	L625V 2D AISynGAP1 missense variant L625V is listed in ClinVar with an uncertain significance (ClinVar ID 3392716.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000					Uncertain		1				-11.319	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	1.80	Ambiguous	0.7	1.69	Ambiguous	1.75	Ambiguous	1.42	Destabilizing	0.480	Likely Benign	-2.96	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.07	Benign	0.01	Affected			0.1306	0.3427		2	1	0.4	-14.03
c.1283A>G	Y428C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments show the SGM‑Consensus result as “Likely Pathogenic,” Foldetta predicts a destabilizing, pathogenic effect, while AlphaMissense‑Optimized is uncertain. No prediction or stability result is missing; the only inconclusive outcome is the AlphaMissense‑Optimized score. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-11.312	Likely Pathogenic	0.852	Likely Pathogenic	Ambiguous	2.82	Destabilizing	0.0	2.99	Destabilizing	2.91	Destabilizing	2.02	Destabilizing	0.454	Likely Benign	-8.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.39	Benign	0.01	Affected			0.3322	0.2220		0	-2	3.8	-60.04
c.535G>A	E179K 2D AIThe SynGAP1 missense variant E179K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (five pathogenic vs. four benign) indicate a pathogenic impact. No ClinVar entry contradicts this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-11.305	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.174	Likely Benign	-2.32	Neutral	0.596	Possibly Damaging	0.202	Benign	4.03	Benign	0.02	Affected			0.2867	0.7695		0	1	-0.4	-0.94
c.1828C>G	L610V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L610V is reported in gnomAD (ID 6‑33440880‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, while only AlphaMissense‑Optimized predicts a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates benign, whereas the SGM Consensus remains pathogenic and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. With the overwhelming majority of tools predicting pathogenicity and no ClinVar evidence to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-G	3	1.86e-6	-11.304	Likely Pathogenic	0.474	Ambiguous	Likely Benign	2.24	Destabilizing	0.3	0.76	Ambiguous	1.50	Ambiguous	1.21	Destabilizing	0.740	Likely Pathogenic	-2.86	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.46	Pathogenic	0.01	Affected	3.37	35	0.1515	0.3039		1	2	0.4	-14.03
c.494G>T	S165I 2D AISynGAP1 missense variant S165I has no ClinVar record and is absent from gnomAD. Individual prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the majority of single‑tool predictions favor a benign effect, whereas the consensus score suggests pathogenicity. Consequently, the variant is most likely benign according to the bulk of evidence, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-11.304	Likely Pathogenic	0.774	Likely Pathogenic	Likely Benign										0.259	Likely Benign	-2.53	Deleterious	0.084	Benign	0.031	Benign	3.96	Benign	0.00	Affected			0.0943	0.5027		-1	-2	5.3	26.08
c.3639C>A	N1213K 2D AIThe SynGAP1 missense variant N1213K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are limited: AlphaMissense‑Optimized yields an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta data are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign) points toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which contains no entry for this variant. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.580690	Disordered	0.521638	Binding	0.888	0.561	0.500											-11.303	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous										0.059	Likely Benign	-1.58	Neutral	0.920	Possibly Damaging	0.652	Possibly Damaging	2.75	Benign	0.05	Affected			0.1506	0.3250		1	0	-0.4	14.07
c.3639C>G	N1213K 2D AIThe SynGAP1 missense variant N1213K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are limited: AlphaMissense‑Optimized yields an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta data are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign) points toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which contains no entry for this variant. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.580690	Disordered	0.521638	Binding	0.888	0.561	0.500											-11.303	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous										0.058	Likely Benign	-1.58	Neutral	0.920	Possibly Damaging	0.652	Possibly Damaging	2.75	Benign	0.05	Affected			0.1506	0.3250		1	0	-0.4	14.07
c.647A>T	Q216L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216L is not reported in ClinVar (ClinVar ID: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain (treated as unavailable), SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the majority of tools (8 pathogenic vs. 5 benign) and the consensus high‑accuracy prediction lean toward pathogenicity. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-11.303	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	-0.17	Likely Benign	0.3	0.28	Likely Benign	0.06	Likely Benign	0.30	Likely Benign	0.797	Likely Pathogenic	-5.58	Deleterious	0.963	Probably Damaging	0.452	Possibly Damaging	5.87	Benign	0.01	Affected			0.1036	0.6410		-2	-2	7.3	-14.97
c.1699G>C	E567Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that agree on a pathogenic effect are SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from AlphaMissense‑Optimized, Foldetta, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta’s stability prediction is also uncertain. Overall, more tools (7) predict pathogenicity than benign (5), with three inconclusive. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-11.302	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.1	1.50	Ambiguous	0.77	Ambiguous	0.33	Likely Benign	0.345	Likely Benign	-2.82	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	3.47	Benign	0.14	Tolerated			0.1029	0.5391		2	2	0.0	-0.98
c.2152C>T	L718F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718F lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools cluster into two groups: benign predictions are made only by REVEL, whereas the remaining tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity; premPS is uncertain and is not counted as evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the overwhelming consensus of these predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.302	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.87	Destabilizing	0.2	2.64	Destabilizing	3.26	Destabilizing	0.78	Ambiguous	0.347	Likely Benign	-3.73	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0590	0.2979		2	0	-1.0	34.02
c.464G>T	S155I 2D AIThe SynGAP1 missense variant S155I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and the Foldetta stability analysis is unavailable. Taken together, the majority of evidence points to a pathogenic impact for S155I. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.298	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.70	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	3.81	Benign	0.00	Affected			0.0764	0.5711		-1	-2	5.3	26.08
c.424A>C	K142Q 2D AIThe SynGAP1 missense variant K142Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-11.295	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-2.50	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.50	Benign	0.00	Affected			0.4232	0.1132		1	1	0.4	-0.04
c.1949A>G	N650S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N650S lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or inconclusive results come from AlphaMissense‑Optimized, FoldX, Rosetta, Foldetta, and premPS. For high‑accuracy methods, AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta is uncertain. Overall, the majority of available predictions support a pathogenic effect. The variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.361944	Uncertain	0.961	0.357	0.000											-11.291	Likely Pathogenic	0.916	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.2	1.43	Ambiguous	1.11	Ambiguous	0.77	Ambiguous	0.395	Likely Benign	-4.98	Deleterious	0.996	Probably Damaging	0.606	Possibly Damaging	3.06	Benign	0.02	Affected			0.3791	0.5090		1	1	2.7	-27.03
c.1475A>G	K492R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K492R is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of tools (seven pathogenic vs. six benign) lean toward a pathogenic interpretation, and this does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-11.290	Likely Pathogenic	0.599	Likely Pathogenic	Likely Benign	-0.20	Likely Benign	0.1	0.45	Likely Benign	0.13	Likely Benign	0.84	Ambiguous	0.487	Likely Benign	-2.98	Deleterious	0.997	Probably Damaging	0.990	Probably Damaging	3.25	Benign	0.05	Affected			0.3911	0.0835		3	2	-0.6	28.01
c.3760G>A	E1254K 2D AIThe SynGAP1 missense variant E1254K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1254K. This prediction is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-11.288	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-2.97	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.36	Pathogenic	0.02	Affected			0.1653	0.5488		0	1	-0.4	-0.94
c.1924A>G	K642E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K642E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. No prediction is inconclusive. Overall, the majority of tools lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.287	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.26	Likely Benign	0.1	-0.13	Likely Benign	0.07	Likely Benign	0.40	Likely Benign	0.404	Likely Benign	-3.92	Deleterious	0.116	Benign	0.011	Benign	2.96	Benign	0.03	Affected			0.3865	0.1013		0	1	0.4	0.94
c.3608A>C	H1203P 2D AIThe SynGAP1 missense variant H1203P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.618285	Disordered	0.527023	Binding	0.892	0.589	0.250											-11.286	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.485	Likely Benign	-2.10	Neutral	0.975	Probably Damaging	0.767	Possibly Damaging	5.47	Benign	0.26	Tolerated			0.1742	0.2820		0	-2	1.6	-40.02
c.1354G>C	V452L 2D 3DClick to see structure in 3D Viewer AISynGAP1 V452L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Because the majority of tools (six) predict benign and the high‑accuracy Foldetta also supports benign, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000											-11.285	Likely Pathogenic	0.929	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.1	-0.25	Likely Benign	0.02	Likely Benign	0.34	Likely Benign	0.316	Likely Benign	-2.96	Deleterious	0.947	Possibly Damaging	0.851	Possibly Damaging	3.54	Benign	0.11	Tolerated			0.0777	0.4061		2	1	-0.4	14.03
c.3743T>G	L1248R 2D AIThe SynGAP1 missense variant L1248R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-11.285	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.370	Likely Benign	-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.1222	0.0488		-3	-2	-8.3	43.03
c.1325A>C	K442T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K442T missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a benign stability change; AlphaMissense‑Optimized remains inconclusive. Overall, the predictions are evenly split, with no single consensus. Thus, the variant is most likely benign based on the majority of evidence, and this assessment does not contradict any ClinVar record (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.273	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous	0.30	Likely Benign	0.2	0.21	Likely Benign	0.26	Likely Benign	0.22	Likely Benign	0.330	Likely Benign	-5.01	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.43	Benign	0.07	Tolerated			0.1510	0.2859		0	-1	3.2	-27.07
c.1780T>A	F594I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594I is not reported in ClinVar and has no entries in gnomAD. In silico assessment shows that all evaluated pathogenicity predictors—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the substitution as pathogenic, while FoldX, Rosetta, and Foldetta provide inconclusive results. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Consequently, the overwhelming majority of predictions point to a pathogenic impact. The variant is therefore most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.271	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.93	Ambiguous	0.1	1.67	Ambiguous	1.80	Ambiguous	1.61	Destabilizing	0.935	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.91	Pathogenic	0.02	Affected			0.1694	0.1925		1	0	1.7	-34.02
c.572G>T	S191I 2D AIThe SynGAP1 missense variant S191I is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. When the predictions are grouped by consensus, four tools favor benign and four favor pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Taken together, the majority of evidence, including the SGM Consensus, points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-11.271	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous										0.283	Likely Benign	-4.51	Deleterious	0.421	Benign	0.086	Benign	3.76	Benign	0.00	Affected			0.0954	0.6842		-1	-2	5.3	26.08
c.1780T>C	F594L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX (uncertain), Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while only FoldX and Foldetta are inconclusive. In the high‑accuracy subset, AlphaMissense‑Optimized remains pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is uncertain. No tools predict a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.270	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.41	Destabilizing	1.96	Ambiguous	1.56	Destabilizing	0.940	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.98	Pathogenic	0.03	Affected			0.1790	0.2439		2	0	1.0	-34.02
c.1782C>A	F594L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX (uncertain), Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while only FoldX and Foldetta are inconclusive. In the high‑accuracy subset, AlphaMissense‑Optimized remains pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is uncertain. No tools predict a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.270	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.41	Destabilizing	1.96	Ambiguous	1.56	Destabilizing	0.893	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.98	Pathogenic	0.03	Affected			0.1790	0.2439		2	0	1.0	-34.02
c.1782C>G	F594L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity; SGM‑Consensus also indicates a likely pathogenic outcome. No tool in the dataset predicts a benign effect. Stability‑focused methods give mixed results: FoldX is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, so these do not provide decisive evidence. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Overall, the consensus of available predictions strongly suggests that F594L is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.270	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.41	Destabilizing	1.96	Ambiguous	1.56	Destabilizing	0.893	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.98	Pathogenic	0.03	Affected			0.1790	0.2439		2	0	1.0	-34.02
c.959T>A	V320D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V320D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL and SIFT; pathogenic predictions from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods FoldX and Rosetta returned uncertain results, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also yielded an uncertain prediction. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status because ClinVar has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.419626	Uncertain	0.905	0.266	0.125											-11.269	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.99	Ambiguous	1.0	1.67	Ambiguous	1.83	Ambiguous	1.50	Destabilizing	0.405	Likely Benign	-5.58	Deleterious	0.999	Probably Damaging	0.972	Probably Damaging	1.93	Pathogenic	0.07	Tolerated			0.1101	0.0482		-2	-3	-7.7	15.96
c.1516C>T	L506F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; premPS and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification and does not contradict the available data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000					Uncertain		1				-11.262	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	4.92	Destabilizing	0.8	5.76	Destabilizing	5.34	Destabilizing	0.91	Ambiguous	0.464	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.01	Affected	3.37	35	0.0566	0.1471		0	2	-1.0	34.02
c.1232T>C	I411T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I411T missense variant is not reported in ClinVar (status: None) and has no entries in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta’s assessment is uncertain. High‑accuracy methods give consistent pathogenic predictions: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-11.258	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.86	Destabilizing	0.0	1.75	Ambiguous	2.31	Destabilizing	1.86	Destabilizing	0.579	Likely Pathogenic	-4.54	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.31	Benign	0.00	Affected			0.0903	0.1389		0	-1	-5.2	-12.05
c.1376G>A	G459D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G459D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate benign effects include REVEL and FATHMM, while the majority of tools predict pathogenicity: FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as inconclusive. Overall, the evidence points to a pathogenic effect for G459D, and this conclusion does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-11.258	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.21	Destabilizing	0.1	0.56	Ambiguous	1.39	Ambiguous	0.93	Ambiguous	0.454	Likely Benign	-6.18	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.07	Benign	0.05	Affected			0.1466	0.1905		1	-1	-3.1	58.04
c.1412C>A	S471Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S471Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, premPS, and AlphaMissense‑Optimized; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The high‑accuracy AlphaMissense‑Optimized scores the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, returns an uncertain stability change. No evidence from ClinVar contradicts these computational assessments. Overall, the preponderance of pathogenic predictions and the SGM Consensus suggest the variant is most likely pathogenic, consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.305330	Structured	0.355411	Uncertain	0.888	0.261	0.000											-11.257	Likely Pathogenic	0.493	Ambiguous	Likely Benign	-0.33	Likely Benign	0.1	-1.31	Ambiguous	-0.82	Ambiguous	0.19	Likely Benign	0.446	Likely Benign	-4.79	Deleterious	0.980	Probably Damaging	0.584	Possibly Damaging	-1.27	Pathogenic	0.03	Affected			0.0607	0.4417		-3	-2	-0.5	76.10
c.1444C>T	L482F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX and premPS, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as Uncertain, SGM Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L482F. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.257	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.48	Likely Benign	0.0	1.09	Ambiguous	0.79	Ambiguous	0.43	Likely Benign	0.724	Likely Pathogenic	-3.95	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	-1.22	Pathogenic	0.01	Affected			0.0457	0.1814		2	0	-1.0	34.02
c.1698G>C	K566N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while Rosetta is uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-11.255	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.83	Destabilizing	0.3	1.33	Ambiguous	2.08	Destabilizing	1.32	Destabilizing	0.683	Likely Pathogenic	-4.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.03	Affected	3.37	35	0.3042	0.1567		0	1	0.4	-14.07
c.1698G>T	K566N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566N is listed in gnomAD (variant ID 6‑33440750‑G‑T) but has no ClinVar entry. All available in‑silico predictors that provide a definitive call classify the substitution as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tool with an inconclusive result is Rosetta (Uncertain), which is treated as unavailable evidence. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on current predictions, and this conclusion does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000								6-33440750-G-T			-11.255	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.83	Destabilizing	0.3	1.33	Ambiguous	2.08	Destabilizing	1.32	Destabilizing	0.683	Likely Pathogenic	-4.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.03	Affected	3.37	35	0.3042	0.1567		0	1	0.4	-14.07
c.749T>G	V250G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V250G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default, while only FATHMM predicts a benign outcome. Uncertain results are reported by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is pathogenic. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.244075	Uncertain	0.778	0.324	0.125											-11.255	Likely Pathogenic	0.917	Likely Pathogenic	Ambiguous	1.65	Ambiguous	0.3	3.18	Destabilizing	2.42	Destabilizing	2.08	Destabilizing	0.900	Likely Pathogenic	-5.90	Deleterious	0.879	Possibly Damaging	0.997	Probably Damaging	5.75	Benign	0.00	Affected			0.1884	0.1996		-1	-3	-4.6	-42.08
c.1030G>A	G344S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G344S is listed in ClinVar (ID 981240.0) as Pathogenic and is not reported in gnomAD. Prediction tools that assess pathogenicity all agree: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic; the only inconclusive result is premPS, which is marked Uncertain. No tool predicts a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.264545	Structured	0.368110	Uncertain	0.913	0.485	0.250					Pathogenic		5				-11.254	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	9.02	Destabilizing	0.7	6.08	Destabilizing	7.55	Destabilizing	0.98	Ambiguous	0.790	Likely Pathogenic	-5.28	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.45	Pathogenic	0.04	Affected	3.37	25	0.2735	0.5324		1	0	-0.4	30.03	217.3	-51.7	0.0	0.1	0.2	0.1			X				X	Potentially Pathogenic	Because Gly344 lacks a proper side chain, it allows the anti-parallel β sheet strand (res. Gly341-Pro349) to have a slight twist. Within a β strand, side chains normally alternate between outward and inward positions, but glycine is an exception as it allows the alternating pattern to skip a residue. Introducing serine or any other residue with a side chain at position 344 prevents this unique skip in the alternating pattern, causing structural strain or likely preventing correct folding altogether. Additionally, Tyr342 shields Gly344 from the solvent, contributing to twist formation in the β sheet and stabilizing the β-strand.In the variant simulations, the side chain of Ser344 assumes the inward position. However, the hydrophobic niche formed by multiple C2 domain residues (e.g., Val365, Val343, Leu327) is not accommodating for its hydroxyl group. The outward position, not seen in the simulations, would be equally disadvantageous due to the presence of hydrophobic residues on that side as well (e.g., Leu345, Tyr342). Serine is also not well-suited for twist formation, as it tends to suppress twisting and bending in β sheets. At this position, the hydroxyl group of Ser344 could also form hydrogen bonds with the backbone atoms of the Gly-rich Ω loop in the C2 domain (e.g., Thr366, Leu367, Gly378; res. Pro364-Pro398), potentially adversely affecting membrane-loop dynamics and ultimately compromising the stability of the SynGAP-membrane association.
c.1801G>T	A601S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A601S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, and premPS—return uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie and thus inconclusive. Foldetta, which integrates FoldX‑MD and Rosetta outputs, also yields an uncertain result. Overall, more tools (six) predict pathogenicity than benign (three), and no ClinVar evidence contradicts this assessment. Therefore, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000											-11.248	Likely Pathogenic	0.136	Likely Benign	Likely Benign	0.79	Ambiguous	0.1	1.63	Ambiguous	1.21	Ambiguous	0.79	Ambiguous	0.541	Likely Pathogenic	-2.99	Deleterious	0.983	Probably Damaging	0.993	Probably Damaging	2.56	Benign	0.01	Affected			0.2732	0.4730		1	1	-2.6	16.00
c.544T>A	S182T 2D AIThe SynGAP1 missense variant S182T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of available predictions (five benign vs three pathogenic) suggest a benign impact. This consensus does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Thus, based on current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-11.247	Likely Pathogenic	0.857	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-2.29	Neutral	0.231	Benign	0.081	Benign	3.68	Benign	0.00	Affected			0.1624	0.5657		1	1	0.1	14.03
c.431C>T	T144M 2D AIThe SynGAP1 missense variant T144M is listed in ClinVar with an “Uncertain” status (ClinVar ID 2231966.0) and is present in the gnomAD database (gnomAD ID 6‑33432728‑C‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of computational predictions lean toward a pathogenic impact, and this assessment does not contradict the ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625					Uncertain		2	6-33432728-C-T	2	1.30e-6	-11.228	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous										0.118	Likely Benign	-3.16	Deleterious	0.913	Possibly Damaging	0.333	Benign	3.73	Benign	0.00	Affected	3.61	5	0.1504	0.6510		-1	-1	2.6	30.09
c.3656A>C	Y1219S 2D AIThe SynGAP1 missense variant Y1219S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-11.227	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.424	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.18	Pathogenic	0.00	Affected			0.5047	0.1403	Weaken	-3	-2	0.5	-76.10
c.731A>C	E244A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244A missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, and FATHMM, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-11.227	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.1	-0.45	Likely Benign	-0.03	Likely Benign	0.82	Ambiguous	0.865	Likely Pathogenic	-4.99	Deleterious	0.970	Probably Damaging	0.584	Possibly Damaging	5.74	Benign	0.01	Affected			0.2672	0.4926		0	-1	5.3	-58.04
c.833A>C	K278T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any ClinVar annotation because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-11.227	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.85	Ambiguous	0.2	-0.08	Likely Benign	0.39	Likely Benign	0.46	Likely Benign	0.484	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.70	Pathogenic	0.04	Affected			0.1775	0.2220		0	-1	3.2	-27.07
c.946A>T	N316Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316Y is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign impact. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-11.226	Likely Pathogenic	0.767	Likely Pathogenic	Likely Benign	0.53	Ambiguous	0.5	-0.09	Likely Benign	0.22	Likely Benign	0.50	Likely Benign	0.454	Likely Benign	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.81	Pathogenic	0.01	Affected			0.0574	0.6971		-2	-2	2.2	49.07
c.930G>C	E310D 2D 3DClick to see structure in 3D Viewer AISynGAP1 E310D is reported in ClinVar (ID 975473.0) as Pathogenic and is not found in gnomAD. Prediction tools that assess the variant’s effect all converge on a deleterious outcome: REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, leaving no tool in the benign category. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also reports Pathogenic. The single uncertain result from FoldX is treated as unavailable. Overall, the variant is most likely pathogenic, and this assessment is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125					Likely Pathogenic		1				-11.218	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.5	2.39	Destabilizing	2.13	Destabilizing	1.04	Destabilizing	0.666	Likely Pathogenic	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.19	Pathogenic	0.02	Affected	3.38	19	0.1981	0.5222		3	2	0.0	-14.03	232.6	27.2	0.1	0.0	0.1	0.1						X		Potentially Benign	The carboxylate group of Glu310, located in an anti-parallel β sheet strand (res. Thr305-Asn315), is ideally positioned to interact with the hydroxyl and backbone amide groups of Thr295 on a twisted anti-parallel β strand. Because the carboxylate group can also interact with the GAP domain residues (e.g., Gln612, Tyr614), Glu310 potentially plays a key role in maintaining the tertiary assembly between the C2 and GAP domains. In the variant simulations, the carboxylate group of Asp310 can form the same interactions as glutamate; however, due to its one hydrocarbon shorter length, the connections are less stable or less optimal.
c.930G>T	E310D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E310D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity uniformly favor a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL (Pathogenic), Rosetta (Pathogenic), Foldetta (Pathogenic), premPS (Pathogenic), PROVEAN (Pathogenic), polyPhen‑2 HumDiv (Pathogenic), polyPhen‑2 HumVar (Pathogenic), SIFT (Pathogenic), ESM1b (Pathogenic), FATHMM (Pathogenic), AlphaMissense‑Default (Pathogenic), and AlphaMissense‑Optimized (Pathogenic). No tool predicts a benign outcome; the only inconclusive result is FoldX (Uncertain). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for E310D. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125											-11.218	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.5	2.39	Destabilizing	2.13	Destabilizing	1.04	Destabilizing	0.666	Likely Pathogenic	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.19	Pathogenic	0.02	Affected	3.38	19	0.1981	0.5222		3	2	0.0	-14.03	232.6	27.2	0.1	0.0	0.1	0.1						X		Potentially Benign	The carboxylate group of Glu310, located in an anti-parallel β sheet strand (res. Thr305-Asn315), is ideally positioned to interact with the hydroxyl and backbone amide groups of Thr295 on a twisted anti-parallel β strand. Because the carboxylate group can also interact with the GAP domain residues (e.g., Gln612, Tyr614), Glu310 potentially plays a key role in maintaining the tertiary assembly between the C2 and GAP domains. In the variant simulations, the carboxylate group of Asp310 can form the same interactions as glutamate; however, due to its one hydrocarbon shorter length, the connections are less stable or less optimal.
c.1421A>G	D474G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D474G is not reported in ClinVar and is present in gnomAD (ID 6‑33438453‑A‑G). Functional prediction tools show a split: benign calls come from FoldX, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta remains uncertain. High‑accuracy assessments give a pathogenic verdict from AlphaMissense‑Optimized and a pathogenic consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000								6-33438453-A-G	1	6.20e-7	-11.215	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic	-0.38	Likely Benign	0.0	0.82	Ambiguous	0.22	Likely Benign	0.44	Likely Benign	0.823	Likely Pathogenic	-6.13	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.28	Pathogenic	0.07	Tolerated	3.37	34	0.3245	0.4933		-1	1	3.1	-58.04
c.1058T>G	L353R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353R is not reported in ClinVar and is absent from gnomAD. In silico predictors largely agree on a deleterious effect: benign predictions are limited to REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all classify the variant as pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is uncertain, SGM‑Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction contradicts the ClinVar status, which is currently unreported. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-11.213	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	3.60	Destabilizing	0.5	2.48	Destabilizing	3.04	Destabilizing	1.91	Destabilizing	0.444	Likely Benign	-4.15	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.33	Pathogenic	0.01	Affected			0.1304	0.1145		-3	-2	-8.3	43.03
c.1202G>A	R401Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438107‑G‑A). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of evaluated algorithms (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta’s stability prediction is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that R401Q is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000					Uncertain		2	6-33438107-G-A			-11.213	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.1	1.50	Ambiguous	1.23	Ambiguous	1.20	Destabilizing	0.780	Likely Pathogenic	-3.69	Deleterious	0.999	Probably Damaging	0.978	Probably Damaging	5.47	Benign	0.04	Affected	3.38	27	0.3234	0.2269		1	1	1.0	-28.06
c.1390T>A	F464I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, while all other evaluated algorithms—including SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-11.210	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	4.77	Destabilizing	0.2	4.35	Destabilizing	4.56	Destabilizing	1.23	Destabilizing	0.539	Likely Pathogenic	-5.97	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.44	Benign	0.03	Affected			0.1439	0.2002		1	0	1.7	-34.02
c.491G>A	R164Q 2D AISynGAP1 missense variant R164Q is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33432788‑G‑A). Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are not available. Overall, the balance of evidence slightly favors a benign interpretation, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.512396	Binding	0.317	0.666	0.250					Uncertain		1	6-33432788-G-A	2	1.24e-6	-11.208	Likely Pathogenic	0.600	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.86	Neutral	0.957	Probably Damaging	0.342	Benign	3.82	Benign	0.00	Affected	3.74	4	0.3607	0.2711		1	1	1.0	-28.06
c.1575G>C	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are therefore not used to weigh the overall assessment. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, while Foldetta predicts benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for E525D. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.1575G>T	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the balance of evidence (nine pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.769A>G	S257G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S257G is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD status: None). Prediction tools that agree on a benign effect include SIFT, FATHMM, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates a benign change, whereas the SGM‑Consensus (majority vote) indicates likely pathogenic. The Foldetta stability prediction is unavailable and therefore does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the lack of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.258293	Uncertain	0.847	0.272	0.250											-11.206	Likely Pathogenic	0.624	Likely Pathogenic	Likely Benign	0.61	Ambiguous	0.3	0.60	Ambiguous	0.61	Ambiguous	0.62	Ambiguous	0.703	Likely Pathogenic	-2.95	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	5.79	Benign	0.11	Tolerated			0.2087	0.3589		1	0	0.4	-30.03
c.1086G>C	W362C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362C is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on the consensus of all predictions, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-11.200	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.1	4.06	Destabilizing	3.87	Destabilizing	1.00	Destabilizing	0.618	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.24	Pathogenic	0.00	Affected			0.4158	0.1622		-8	-2	3.4	-83.07
c.1086G>T	W362C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362C is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact on protein stability. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-11.200	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.1	4.06	Destabilizing	3.87	Destabilizing	1.00	Destabilizing	0.618	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.24	Pathogenic	0.00	Affected			0.4158	0.1622		-8	-2	3.4	-83.07
c.2065C>A	L689I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar, while those that predict a pathogenic effect are polyPhen2_HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also unavailable. No folding‑stability evidence supports a deleterious change. Overall, the balance of evidence slightly favors a benign interpretation, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-11.196	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.71	Ambiguous	0.1	1.12	Ambiguous	1.42	Ambiguous	0.85	Ambiguous	0.180	Likely Benign	-1.97	Neutral	0.822	Possibly Damaging	0.381	Benign	3.44	Benign	0.00	Affected			0.0921	0.3479		2	2	0.7	0.00
c.1819C>G	L607V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607V is listed in ClinVar with an uncertain significance (ClinVar ID 1450275.0) and is present in gnomAD (ID 6‑33440871‑C‑G). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized reports benign, whereas the SGM‑Consensus, derived from the majority of pathogenic predictions, indicates pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore not considered evidence. Overall, the preponderance of computational evidence points to a pathogenic effect for L607V, a conclusion that contrasts with the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000					Uncertain		2	6-33440871-C-G	2	1.24e-6	-11.190	Likely Pathogenic	0.637	Likely Pathogenic	Likely Benign	1.04	Ambiguous	0.2	1.36	Ambiguous	1.20	Ambiguous	0.90	Ambiguous	0.715	Likely Pathogenic	-2.99	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.50	Pathogenic	0.01	Affected	3.37	35	0.1634	0.3577		2	1	0.4	-14.03	216.3	28.1	0.1	0.0	0.9	0.2				X				Potentially Benign	Leu607 is located in a short helical region (res. Ser606-Phe608) within an α-α loop connecting two α helices (res. Glu582-Met603 and res. Glu617-Asn635). In the WT simulations, the iso-butyl side chain of Leu607 does not interact with any other residues, but it could potentially interact directly with Ras due to its location at the GAP domain.In the variant simulations, Val607, which has similar size and physicochemical properties to leucine, does not cause any negative effects on the protein structure. However, due to its location at the GAP-Ras interface, the residue swap could affect the complex formation with the GTPase, but this cannot be investigated using solvent-only simulations.
c.1993T>A	Y665N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y665N variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of conventional predictors lean toward a benign impact, and this assessment does not contradict ClinVar status (none). Thus, the variant is most likely benign based on the prevailing predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-11.189	Likely Pathogenic	0.470	Ambiguous	Likely Benign	1.11	Ambiguous	0.1	1.43	Ambiguous	1.27	Ambiguous	0.50	Likely Benign	0.219	Likely Benign	-3.03	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.88	Tolerated			0.1929	0.0573		-2	-2	-2.2	-49.07
c.1379A>C	K460T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K460T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) yield uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD/Rosetta analysis remains inconclusive. Overall, the majority of evidence points to a pathogenic impact for K460T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.187	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.1	1.16	Ambiguous	1.20	Ambiguous	0.77	Ambiguous	0.208	Likely Benign	-5.02	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.35	Benign	0.07	Tolerated			0.1858	0.3848		0	-1	3.2	-27.07
c.1244A>T	E415V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415V missense variant is not reported in ClinVar or gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts benign. No evidence is missing or inconclusive. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-11.182	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.56	Ambiguous	0.2	0.14	Likely Benign	0.35	Likely Benign	0.40	Likely Benign	0.441	Likely Benign	-6.52	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.13	Benign	0.02	Affected			0.0650	0.4218		-2	-2	7.7	-29.98
c.1723C>T	R575C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R575C is listed in ClinVar with an “Uncertain” status (ClinVar ID 537013.0) and is present in gnomAD (ID 6‑33440775‑C‑T). Prediction tools that indicate a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Four tools (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of predictions support a pathogenic effect. Thus, the variant is most likely pathogenic, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000					Conflicting		3	6-33440775-C-T	23	1.43e-5	-11.179	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	1.39	Ambiguous	0.2	0.50	Ambiguous	0.95	Ambiguous	0.73	Ambiguous	0.715	Likely Pathogenic	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.30	Pathogenic	0.02	Affected	3.37	35	0.2969	0.1692		-4	-3	7.0	-53.05	227.7	99.2	0.0	0.0	0.0	0.1		X						Potentially Pathogenic	The guanidinium group of Arg575, located in an α-helix (res. Arg563-Glu578), forms salt bridges with the carboxylate groups of Asp463 and Asp467, and it also hydrogen bonds with the hydroxyl group of Ser466 on an opposing α-helix (res. Ala461-Phe476) in the WT simulations. In the variant simulations, the thiol group of the Cys575 side chain, which is neither positively charged nor particularly hydrophilic, packs against the hydrophobic Met470 on an opposing α-helix (res. Ala461-Arg475). Additionally, although the thiol group is not an effective hydrogen bonder, the Cys575 side chain rotates to hydrogen bond with the backbone carbonyl group of Ser571 in the same α-helix, which could theoretically lower the helix integrity. Overall, the residue swap has the potential to substantially affect the tertiary structure assembly during the protein folding process.
c.1570T>A	C524S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524S is listed in gnomAD (variant ID 6‑33438813‑T‑A) but has no ClinVar entry. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome, while FoldX, Rosetta, and Foldetta are uncertain and therefore not counted as evidence. Grouping by agreement yields a benign‑prediction set that is empty and a pathogenic‑prediction set that contains the eleven tools above. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta remains uncertain. Consequently, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125								6-33438813-T-A	1	6.20e-7	-11.174	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.1	1.55	Ambiguous	1.18	Ambiguous	1.58	Destabilizing	0.915	Likely Pathogenic	-9.94	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.38	Pathogenic	0.00	Affected	3.37	35	0.5362	0.1848	Weaken	-1	0	-3.3	-16.06
c.1571G>C	C524S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 C524S variant has no ClinVar entry and is not present in gnomAD. Prediction tools that agree on a benign effect are none; those that predict pathogenicity include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta returned inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-11.174	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.1	1.55	Ambiguous	1.18	Ambiguous	1.58	Destabilizing	0.904	Likely Pathogenic	-9.94	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.38	Pathogenic	0.00	Affected	3.37	35	0.5362	0.1848	Weaken	-1	0	-3.3	-16.06
c.3618A>C	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3618A>T	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.875C>T	A292V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain and therefore not counted. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-11.170	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	0.5	4.60	Destabilizing	3.32	Destabilizing	0.85	Ambiguous	0.430	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.03	Affected			0.1272	0.6253		0	0	2.4	28.05
c.2165G>T	S722I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S722I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, premPS, SIFT, and the folding‑stability method Foldetta, whereas pathogenic predictions are reported by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are provided by AlphaMissense‑Optimized, FoldX, and Rosetta. High‑accuracy analyses further clarify the picture: AlphaMissense‑Optimized remains inconclusive; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign impact on protein stability. Overall, the majority of evidence leans toward a pathogenic interpretation, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-11.165	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.69	Ambiguous	0.1	-0.65	Ambiguous	0.02	Likely Benign	0.18	Likely Benign	0.232	Likely Benign	-3.88	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.48	Pathogenic	0.07	Tolerated			0.0776	0.4187		-1	-2	5.3	26.08
c.3665G>C	R1222T 2D AIThe SynGAP1 missense variant R1222T is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R1222T is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.164	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.407	Likely Benign	-4.39	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.13	Tolerated			0.1550	0.2851		-1	-1	3.8	-55.08
c.947A>T	N316I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and premPS, whereas the majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. No prediction is missing or inconclusive beyond the uncertain AlphaMissense‑Optimized result. Based on the preponderance of pathogenic predictions and the high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-11.164	Likely Pathogenic	0.899	Likely Pathogenic	Ambiguous	2.74	Destabilizing	0.2	4.10	Destabilizing	3.42	Destabilizing	0.18	Likely Benign	0.318	Likely Benign	-6.37	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.00	Pathogenic	0.03	Affected			0.0734	0.7422		-2	-3	8.0	-0.94
c.1316T>A	L439Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-11.162	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	2.50	Destabilizing	0.1	2.06	Destabilizing	2.28	Destabilizing	1.35	Destabilizing	0.575	Likely Pathogenic	-5.15	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.21	Benign	0.01	Affected			0.1065	0.0488		-2	-2	-7.3	14.97
c.1276A>G	N426D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Three tools (FoldX, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (six benign vs. four pathogenic) and the two high‑accuracy benign calls suggest the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-11.159	Likely Pathogenic	0.554	Ambiguous	Likely Benign	0.80	Ambiguous	0.0	0.18	Likely Benign	0.49	Likely Benign	0.64	Ambiguous	0.173	Likely Benign	-3.09	Deleterious	0.998	Probably Damaging	0.980	Probably Damaging	3.34	Benign	0.09	Tolerated			0.1730	0.1746		2	1	0.0	0.98
c.1487A>C	E496A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E496A missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, SIFT, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. FoldX is uncertain and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the majority of predictions (8 pathogenic vs. 5 benign) indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000											-11.159	Likely Pathogenic	0.598	Likely Pathogenic	Likely Benign	0.68	Ambiguous	0.0	0.23	Likely Benign	0.46	Likely Benign	0.47	Likely Benign	0.681	Likely Pathogenic	-4.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.41	Pathogenic	0.09	Tolerated			0.2806	0.3548		0	-1	5.3	-58.04
c.701G>T	R234L 2D AIThe SynGAP1 missense variant R234L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy methods show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (7 pathogenic vs. 4 benign) and the pathogenic consensus from the high‑accuracy SGM‑Consensus suggest that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.311558	Uncertain	0.804	0.322	0.000											-11.153	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.38	Ambiguous	0.9	0.50	Ambiguous	0.94	Ambiguous	0.20	Likely Benign	0.734	Likely Pathogenic	-4.64	Deleterious	0.649	Possibly Damaging	0.199	Benign	5.78	Benign	0.11	Tolerated			0.1846	0.4783		-3	-2	8.3	-43.03
c.1980G>A	M660I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M660I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and the protein‑folding stability method Foldetta returns an uncertain result. Stability predictions from FoldX, Rosetta, and premPS are also inconclusive. Overall, the majority of evidence points to a pathogenic effect for M660I. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-11.150	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.1	0.71	Ambiguous	0.93	Ambiguous	0.95	Ambiguous	0.464	Likely Benign	-3.99	Deleterious	0.887	Possibly Damaging	0.289	Benign	3.52	Benign	0.04	Affected			0.1170	0.2878		2	1	2.6	-18.03
c.1980G>C	M660I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M660I (GAP domain) is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No other stability predictions are available. Overall, the preponderance of evidence points to a pathogenic effect for M660I. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-11.150	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.1	0.71	Ambiguous	0.93	Ambiguous	0.95	Ambiguous	0.464	Likely Benign	-3.99	Deleterious	0.887	Possibly Damaging	0.289	Benign	3.52	Benign	0.04	Affected			0.1170	0.2878		2	1	2.6	-18.03
c.1980G>T	M660I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M660I (GAP domain) is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No other stability predictions are available. Overall, the preponderance of evidence points to a pathogenic effect for M660I. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-11.150	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.1	0.71	Ambiguous	0.93	Ambiguous	0.95	Ambiguous	0.464	Likely Benign	-3.99	Deleterious	0.887	Possibly Damaging	0.289	Benign	3.52	Benign	0.04	Affected			0.1170	0.2878		2	1	2.6	-18.03
c.407G>A	R136Q 2D AIThe SynGAP1 R136Q variant is listed in ClinVar as benign and is present in gnomAD (6‑33432704‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑vs‑2 split, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no reported result for this variant. Based on the available predictions, the variant is most likely benign, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.433034	Structured	0.657394	Binding	0.351	0.894	0.250					Benign		1	6-33432704-G-A	13	9.17e-6	-11.146	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-2.26	Neutral	0.957	Probably Damaging	0.342	Benign	3.52	Benign	0.01	Affected	3.61	5	0.3171	0.2460		1	1	1.0	-28.06
c.956C>A	A319D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A319D missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus remains pathogenic. Foldetta, which integrates FoldX‑MD (benign) and Rosetta (uncertain), is considered unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.410405	Uncertain	0.879	0.254	0.125											-11.144	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign	-0.02	Likely Benign	0.2	-0.84	Ambiguous	-0.43	Likely Benign	0.30	Likely Benign	0.373	Likely Benign	-2.38	Neutral	0.998	Probably Damaging	0.966	Probably Damaging	2.01	Pathogenic	0.20	Tolerated			0.1504	0.1360		0	-2	-5.3	44.01
c.1724G>A	R575H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R575H (ClinVar ID 1029088.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33440776‑G‑A). Prediction tools that indicate a benign effect include Rosetta, Foldetta, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, Foldetta as Benign, and the SGM Consensus as Pathogenic. Overall, the majority of evidence points to a pathogenic impact, which contrasts with the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000					Conflicting		4	6-33440776-G-A	204	1.27e-4	-11.142	Likely Pathogenic	0.496	Ambiguous	Likely Benign	0.81	Ambiguous	0.2	-0.22	Likely Benign	0.30	Likely Benign	1.31	Destabilizing	0.707	Likely Pathogenic	-2.34	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.05	Affected	3.37	35	0.2361	0.1292		2	0	1.3	-19.05	244.7	80.6	0.0	0.0	0.3	0.0		X						Potentially Pathogenic	The guanidinium group of Arg575, located in an α-helix (res. Arg563-Glu578), forms salt bridges with the carboxylate groups of Asp463 and Asp467, and it also hydrogen bonds with the hydroxyl group of Ser466 on an opposing α-helix (res. Ala461-Phe476) in the WT simulations. In the variant simulations, the imidazole ring of His575 (in its neutral epsilon protonated form) cannot form the same salt bridges as the guanidinium group of the non-mutated Arg575. Instead, His575 only forms weak hydrogen bonds with the hydroxyl groups of Ser466 and Ser571. Overall, the residue swap has the potential to substantially affect the tertiary structure assembly during the protein folding process.
c.3644A>T	K1215M 2D AIThe SynGAP1 missense variant K1215M is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that K1215M is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-11.140	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.202	Likely Benign	-4.06	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.35	Pathogenic	0.00	Affected			0.0922	0.3085		0	-1	5.8	3.02
c.1043T>A	V348E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348E is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among the majority of tools, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for V348E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-11.135	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.1	2.20	Destabilizing	2.31	Destabilizing	2.14	Destabilizing	0.470	Likely Benign	-5.26	Deleterious	0.989	Probably Damaging	0.637	Possibly Damaging	1.56	Pathogenic	0.01	Affected			0.1089	0.1922		-2	-2	-7.7	29.98
c.689G>T	C230F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Foldetta and premPS give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; Foldetta remains uncertain. Overall, the preponderance of evidence indicates that C230F is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-11.134	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	-0.09	Likely Benign	0.1	-2.03	Stabilizing	-1.06	Ambiguous	0.51	Ambiguous	0.840	Likely Pathogenic	-8.73	Deleterious	0.940	Possibly Damaging	0.641	Possibly Damaging	5.96	Benign	0.03	Affected			0.1329	0.4173		-4	-2	0.3	44.04
c.472C>G	Q158E 2D AIThe SynGAP1 missense variant Q158E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.527565	Binding	0.286	0.750	0.375											-11.133	Likely Pathogenic	0.196	Likely Benign	Likely Benign										0.063	Likely Benign	-0.54	Neutral	0.143	Benign	0.078	Benign	4.20	Benign	0.09	Tolerated			0.1420	0.2223		2	2	0.0	0.98
c.2159A>G	D720G 2D AISynGAP1 missense variant D720G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Foldetta, and premPS, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools remain inconclusive: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-11.130	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.4	0.53	Ambiguous	0.49	Likely Benign	0.46	Likely Benign	0.427	Likely Benign	-5.67	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.15	Pathogenic	0.01	Affected			0.4027	0.5011		1	-1	3.1	-58.04
c.1787G>A	R596H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R596H is listed in ClinVar as benign (ClinVar ID 1989474.0) and is present in gnomAD (ID 6‑33440839‑G‑A). Functional prediction tools largely agree on a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus all report pathogenicity, while only Rosetta predicts a benign outcome. Two tools are inconclusive: AlphaMissense‑Optimized and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the four pathogenic votes) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact, directly contradicting the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.017797	Structured	0.135423	Uncertain	0.918	0.134	0.000					Likely Benign		1	6-33440839-G-A	15	9.29e-6	-11.128	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	3.00	Destabilizing	0.9	0.43	Likely Benign	1.72	Ambiguous	1.35	Destabilizing	0.717	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.43	Pathogenic	0.00	Affected	3.37	35	0.3290	0.1208		2	0	1.3	-19.05	223.5	80.5	-0.1	0.0	-0.1	0.3		X		X				Potentially Pathogenic	The guanidinium group of Arg596, located in an α helix (res. Glu582-Met603), forms a salt bridge with the carboxylate group of Glu495 from another α helix (res. Leu489-Glu519). In the WT simulations, the side chain of Arg596 hydrogen bonds with the backbone carbonyl groups of Asn487, Glu486, Arg485, and Phe484. Additionally, Arg596 can hydrogen bond with the carboxamide group of the Asn487 side chain on an opposing loop that links two α helices (res. Ala461-Arg475, res. Leu489-Glu519).In the variant simulations, the imidazole ring of His596 can form hydrogen bonds with the same residues as arginine; however, these interactions are not as coordinated or strong in comparison. Thus, the residue swap could affect the tertiary structure assembly more profoundly than observed in the simulations. Notably, Arg596 plays a key role in positioning the aforementioned loop, which is crucial for the placement of the “arginine finger” or the Arg485 side chain during RasGTPase activation.
c.1581C>A	D527E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527E missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a strong bias toward pathogenicity: REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, whereas only FoldX and premPS predict a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains Likely Pathogenic. Overall, the preponderance of evidence points to a pathogenic impact, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-11.125	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.8	2.29	Destabilizing	1.33	Ambiguous	0.50	Likely Benign	0.740	Likely Pathogenic	-3.74	Deleterious	0.929	Possibly Damaging	0.938	Probably Damaging	-2.31	Pathogenic	0.02	Affected			0.1103	0.3428		3	2	0.0	14.03
c.1581C>G	D527E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527E missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a strong bias toward pathogenicity: REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, whereas only FoldX and premPS predict a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains Likely Pathogenic. Overall, the preponderance of evidence points to a pathogenic impact, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-11.125	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.8	2.29	Destabilizing	1.33	Ambiguous	0.50	Likely Benign	0.740	Likely Pathogenic	-3.74	Deleterious	0.929	Possibly Damaging	0.938	Probably Damaging	-2.31	Pathogenic	0.02	Affected			0.1103	0.3428		3	2	0.0	14.03
c.2183C>T	P728L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect for P728L. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-11.125	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.0	0.15	Likely Benign	0.47	Likely Benign	0.20	Likely Benign	0.402	Likely Benign	-8.27	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.2321	0.4713		-3	-3	5.4	16.04
c.1723C>A	R575S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R575S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include only SIFT, whereas the majority—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict pathogenicity. FoldX, Rosetta, Foldetta, and premPS give uncertain results, which are treated as unavailable evidence. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R575S, and this assessment does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000											-11.124	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.1	0.55	Ambiguous	1.11	Ambiguous	0.76	Ambiguous	0.582	Likely Pathogenic	-2.71	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.21	Pathogenic	0.33	Tolerated			0.2669	0.2394		0	-1	3.7	-69.11
c.1816A>T	S606C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606C is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign, and the SGM‑Consensus as Likely Pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overall distribution of predictions, the variant is most likely benign, although the SGM‑Consensus suggests pathogenicity; this does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-11.122	Likely Pathogenic	0.774	Likely Pathogenic	Likely Benign	-0.34	Likely Benign	0.0	-0.31	Likely Benign	-0.33	Likely Benign	0.49	Likely Benign	0.348	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.00	Affected			0.0986	0.4580		0	-1	3.3	16.06
c.1997A>C	E666A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: FoldX (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive because FoldX is Uncertain while Rosetta is Benign. Overall, the majority of available predictions (six pathogenic vs. five benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-11.122	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.1	0.18	Likely Benign	0.38	Likely Benign	0.50	Likely Benign	0.407	Likely Benign	-5.15	Deleterious	0.992	Probably Damaging	0.863	Possibly Damaging	3.45	Benign	0.07	Tolerated			0.3950	0.4878		0	-1	5.3	-58.04
c.3677A>T	Q1226L 2D AIThe SynGAP1 missense variant Q1226L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” AlphaMissense‑Optimized is classified as “Uncertain,” and Foldetta’s protein‑folding stability analysis is unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for Q1226L. This conclusion is not contradicted by ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-11.122	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.77	Pathogenic	0.00	Affected			0.0493	0.4282		-2	-2	7.3	-14.97
c.478C>A	L160M 2D AIThe SynGAP1 missense variant L160M is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus is unavailable; and Foldetta, which combines FoldX‑MD and Rosetta stability calculations, has no reported output for this variant. Overall, the balance of evidence leans toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the lack of a ClinVar assertion mean the variant’s clinical significance remains uncertain. This assessment does not contradict any existing ClinVar status, as none is available. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-11.120	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign										0.097	Likely Benign	-0.94	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	3.85	Benign	0.00	Affected			0.0837	0.3613		4	2	-1.9	18.03
c.1436G>T	R479L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R479L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). AlphaMissense‑Optimized is uncertain. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized remains uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No single metric dominates, and the overall evidence is balanced. Therefore, the variant’s pathogenicity is inconclusive; it is not contradicted by ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000											-11.118	Likely Pathogenic	0.832	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.12	Likely Benign	0.29	Likely Benign	0.39	Likely Benign	0.265	Likely Benign	-4.21	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.38	Benign	0.15	Tolerated			0.1326	0.3624		-3	-2	8.3	-43.03
c.1693C>G	L565V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565V has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two consensus groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Two tools (AlphaMissense‑Optimized and Rosetta) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a pathogenic impact on protein stability. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000											-11.118	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	2.69	Destabilizing	0.0	1.37	Ambiguous	2.03	Destabilizing	1.40	Destabilizing	0.303	Likely Benign	-2.99	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.87	Benign	0.03	Affected			0.1558	0.2488		2	1	0.4	-14.03
c.1017G>C	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for K339N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1017G>T	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K339N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact for K339N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1444C>A	L482I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from PROVEAN and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (REVEL, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) indicate pathogenicity. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments give a consistent picture: AlphaMissense‑Optimized predicts a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain outcome. Overall, the preponderance of pathogenic predictions suggests that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.116	Likely Pathogenic	0.760	Likely Pathogenic	Likely Benign	1.29	Ambiguous	0.1	1.90	Ambiguous	1.60	Ambiguous	0.71	Ambiguous	0.600	Likely Pathogenic	-1.97	Neutral	0.994	Probably Damaging	0.994	Probably Damaging	-1.31	Pathogenic	0.05	Affected			0.0677	0.2368		2	2	0.7	0.00
c.3751C>A	Q1251K 2D AIThe SynGAP1 missense variant Q1251K is catalogued in gnomAD (ID 6‑33446743‑C‑A) but has no ClinVar entry. Functional prediction tools show a split: benign calls from REVEL and FATHMM, whereas the majority—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as Uncertain, SGM‑Consensus remains Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875								6-33446743-C-A	1	6.20e-7	-11.113	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous										0.208	Likely Benign	-2.92	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.53	Benign	0.00	Affected	3.77	5	0.1418	0.2635		1	1	-0.4	0.04
c.1336G>C	E446Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E446Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability predictions are available. Overall, the balance of evidence from the consensus of multiple in silico predictors points to a pathogenic classification for E446Q. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-11.107	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign	0.92	Ambiguous	0.5	0.54	Ambiguous	0.73	Ambiguous	0.84	Ambiguous	0.337	Likely Benign	-2.80	Deleterious	0.992	Probably Damaging	0.973	Probably Damaging	3.24	Benign	0.04	Affected			0.1049	0.6218		2	2	0.0	-0.98
c.2150T>A	L717H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L717H occurs in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM; all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overwhelming majority of computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-11.107	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.27	Destabilizing	0.1	2.04	Destabilizing	2.16	Destabilizing	1.05	Destabilizing	0.317	Likely Benign	-5.23	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.29	Benign	0.00	Affected			0.0918	0.0558		-2	-3	-7.0	23.98
c.832A>C	K278Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, whereas Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect, and AlphaMissense‑Optimized remains uncertain. Overall, the majority of evidence points to a pathogenic impact for K278Q, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-11.107	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	0.25	Likely Benign	0.24	Likely Benign	0.73	Ambiguous	0.387	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.71	Pathogenic	0.05	Affected			0.3770	0.0672		1	1	0.4	-0.04
c.1502T>A	I501N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, while a majority of tools (SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Uncertain results come from AlphaMissense‑Optimized, Foldetta, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, whereas the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta likewise remains inconclusive. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-11.105	Likely Pathogenic	0.854	Likely Pathogenic	Ambiguous	2.22	Destabilizing	0.0	1.70	Ambiguous	1.96	Ambiguous	1.90	Destabilizing	0.445	Likely Benign	-6.13	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.37	Benign	0.01	Affected			0.0825	0.0270		-2	-3	-8.0	0.94
c.1706T>A	F569Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F569Y missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive, providing no definitive evidence for either outcome. High‑accuracy assessments show that the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) strongly supports pathogenicity, while AlphaMissense‑Optimized remains uncertain and Foldetta likewise yields an inconclusive result. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-11.101	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.57	Ambiguous	0.1	0.82	Ambiguous	1.20	Ambiguous	1.29	Destabilizing	0.824	Likely Pathogenic	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.37	Pathogenic	0.08	Tolerated			0.1379	0.1170		7	3	-4.1	16.00
c.1280A>C	H427P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Two tools are uncertain: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate a pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification for H427P, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-11.098	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	4.74	Destabilizing	0.1	7.61	Destabilizing	6.18	Destabilizing	0.68	Ambiguous	0.324	Likely Benign	-4.22	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.51	Benign	0.01	Affected			0.2061	0.3442		0	-2	1.6	-40.02
c.146G>A	C49Y 2D AIThe SynGAP1 missense variant C49Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for C49Y. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-11.097	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous										0.312	Likely Benign	-3.38	Deleterious	0.676	Possibly Damaging	0.761	Possibly Damaging	3.85	Benign	0.00	Affected			0.1016	0.3172		0	-2	-3.8	60.04
c.808G>C	E270Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E270Q missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, and premPS, whereas the majority of tools predict pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates several high‑accuracy predictors, classifies the variant as Likely Pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized is Uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. Rosetta alone is Uncertain, and Foldetta’s uncertainty reflects limited stability change evidence. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125											-11.096	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.00	Likely Benign	0.2	1.00	Ambiguous	0.50	Ambiguous	0.46	Likely Benign	0.418	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.65	Pathogenic	0.03	Affected			0.1044	0.4015		2	2	0.0	-0.98
c.928G>C	E310Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E310Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign are Rosetta and Foldetta, whereas the remaining tools—REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict pathogenicity. FoldX and premPS give uncertain results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Likely Pathogenic; Foldetta, a protein‑folding stability approach combining FoldX‑MD and Rosetta, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125											-11.093	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.5	-0.38	Likely Benign	0.39	Likely Benign	0.85	Ambiguous	0.688	Likely Pathogenic	-2.76	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.24	Pathogenic	0.01	Affected			0.1334	0.8341		2	2	0.0	-0.98
c.1349C>G	A450G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A450G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the variant as pathogenic; FoldX is inconclusive. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenic. Overall, the preponderance of evidence indicates that A450G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.306281	Uncertain	0.963	0.234	0.000											-11.090	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign	1.79	Ambiguous	0.0	2.29	Destabilizing	2.04	Destabilizing	1.23	Destabilizing	0.355	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.980	Probably Damaging	3.40	Benign	0.04	Affected			0.1670	0.3078		1	0	-2.2	-14.03
c.866T>G	M289R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No predictions or stability results are missing or inconclusive. Overall, the majority of tools lean toward a pathogenic effect, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-11.090	Likely Pathogenic	0.719	Likely Pathogenic	Likely Benign	0.04	Likely Benign	0.1	0.28	Likely Benign	0.16	Likely Benign	1.01	Destabilizing	0.228	Likely Benign	-2.84	Deleterious	0.989	Probably Damaging	0.767	Possibly Damaging	1.84	Pathogenic	0.08	Tolerated			0.1482	0.0828		0	-1	-6.4	24.99
c.1421A>C	D474A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, SGM Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-11.082	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.08	Likely Benign	0.0	0.15	Likely Benign	0.12	Likely Benign	0.17	Likely Benign	0.757	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.22	Pathogenic	0.22	Tolerated			0.3265	0.4354		0	-2	5.3	-44.01
c.638T>C	I213T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I213T missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining evidence—SGM‑Consensus (Likely Pathogenic), REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently indicates pathogenicity. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence supports a pathogenic classification for I213T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.158265	Structured	0.372201	Uncertain	0.850	0.295	0.125											-11.080	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.46	Ambiguous	0.8	1.32	Ambiguous	1.39	Ambiguous	1.49	Destabilizing	0.882	Likely Pathogenic	-3.99	Deleterious	0.948	Possibly Damaging	0.588	Possibly Damaging	5.82	Benign	0.00	Affected			0.0905	0.0708		0	-1	-5.2	-12.05
c.410T>C	L137P 2D AIThe SynGAP1 missense variant L137P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-11.067	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.377	Likely Benign	-3.77	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.59	Benign	0.00	Affected			0.3620	0.1177		-3	-3	-5.4	-16.04
c.506A>C	D169A 2D AIThe SynGAP1 D169A missense variant is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, the benign set includes REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; the pathogenic set includes PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta predictions are unavailable. Overall, the balance of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125											-11.065	Likely Pathogenic	0.874	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-3.15	Deleterious	0.018	Benign	0.025	Benign	4.10	Benign	0.01	Affected			0.4012	0.6809		0	-2	5.3	-44.01
c.167T>A	L56Q 2D AIThe SynGAP1 missense variant L56Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions (5 pathogenic vs 3 benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-11.064	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous										0.293	Likely Benign	-2.03	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.79	Benign	0.00	Affected			0.1083	0.0842		-2	-2	-7.3	14.97
c.761A>G	K254R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K254R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic, 1 uncertain); Foldetta is uncertain. Taken together, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375											-11.064	Likely Pathogenic	0.528	Ambiguous	Likely Benign	-0.44	Likely Benign	0.1	-1.13	Ambiguous	-0.79	Ambiguous	0.76	Ambiguous	0.604	Likely Pathogenic	-2.36	Neutral	0.970	Probably Damaging	0.681	Possibly Damaging	5.81	Benign	0.09	Tolerated			0.4070	0.1658		3	2	-0.6	28.01
c.2890C>G	H964D 2D AIThe SynGAP1 missense variant H964D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.990547	Disordered	0.982486	Binding	0.364	0.886	0.750											-11.061	Likely Pathogenic	0.207	Likely Benign	Likely Benign										0.124	Likely Benign	-0.45	Neutral	0.000	Benign	0.000	Benign	4.18	Benign	0.24	Tolerated			0.2313	0.2923		1	-1	-0.3	-22.05
c.2102C>G	P701R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P701R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Two tools (FoldX and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000											-11.060	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	0.54	Ambiguous	0.0	-0.19	Likely Benign	0.18	Likely Benign	0.65	Ambiguous	0.088	Likely Benign	-2.09	Neutral	0.784	Possibly Damaging	0.278	Benign	3.41	Benign	0.08	Tolerated			0.1365	0.2500		0	-2	-2.9	59.07
c.2045A>C	Y682S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682S has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y682S, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-11.058	Likely Pathogenic	0.894	Likely Pathogenic	Ambiguous	2.12	Destabilizing	0.1	1.12	Ambiguous	1.62	Ambiguous	0.88	Ambiguous	0.552	Likely Pathogenic	-8.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.42	Benign	0.12	Tolerated			0.4487	0.2343		-3	-2	0.5	-76.10
c.3715G>C	A1239P 2D AIThe SynGAP1 missense variant A1239P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL and polyPhen‑2 HumVar, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that A1239P is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.534779	Binding	0.887	0.542	0.250											-11.055	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.085	Likely Benign	-2.62	Deleterious	0.784	Possibly Damaging	0.390	Benign	2.32	Pathogenic	0.00	Affected			0.1438	0.3450		1	-1	-3.4	26.04
c.1450T>C	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic vs. 1 benign) and therefore also indicates pathogenicity. AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy consensus supports a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.275	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1452C>A	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic vs. 1 benign) and therefore also indicates pathogenicity. AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy consensus supports a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.214	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1452C>G	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy methods reinforce the pathogenic signal. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.214	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1817G>C	S606T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and AlphaMissense‑Optimized, whereas a pathogenic consensus is reached by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain results come from Rosetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools predict pathogenicity, and the SGM Consensus supports this view, while the high‑accuracy methods give mixed results. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-11.052	Likely Pathogenic	0.554	Ambiguous	Likely Benign	0.06	Likely Benign	0.1	-0.91	Ambiguous	-0.43	Likely Benign	0.57	Ambiguous	0.203	Likely Benign	-2.99	Deleterious	0.826	Possibly Damaging	0.933	Probably Damaging	3.34	Benign	0.03	Affected			0.1260	0.4513		1	1	0.1	14.03
c.1483G>C	E495Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E495Q missense variant is not listed in ClinVar and has no reported allele in gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, and Foldetta, all of which score the substitution as benign. Tools that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, AlphaMissense‑Optimized is uncertain, and Foldetta predicts benign stability. Overall, the majority of evidence points to a pathogenic impact. The variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000											-11.050	Likely Pathogenic	0.899	Likely Pathogenic	Ambiguous	-0.27	Likely Benign	0.1	0.11	Likely Benign	-0.08	Likely Benign	0.89	Ambiguous	0.748	Likely Pathogenic	-2.92	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.42	Pathogenic	0.01	Affected			0.1093	0.4973		2	2	0.0	-0.98
c.1832T>G	M611R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M611R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are AlphaMissense‑Optimized, polyPhen2_HumVar, and SIFT. Tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen2_HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is reported as uncertain. No prediction or folding result is missing; all available data are considered. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.236433	Structured	0.210791	Uncertain	0.870	0.253	0.000											-11.050	Likely Pathogenic	0.642	Likely Pathogenic	Likely Benign	1.80	Ambiguous	0.8	2.00	Destabilizing	1.90	Ambiguous	1.58	Destabilizing	0.644	Likely Pathogenic	-4.10	Deleterious	0.779	Possibly Damaging	0.159	Benign	-1.21	Pathogenic	0.21	Tolerated			0.1399	0.0837		0	-1	-6.4	24.99
c.1826G>T	G609V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G609V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS and AlphaMissense‑Optimized, whereas the remaining 10 tools (SGM Consensus, REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM) all predict pathogenicity. High‑accuracy assessments further highlight the discordance: AlphaMissense‑Optimized reports a benign effect, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate pathogenicity. With the majority of evidence pointing to deleterious impact, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.203786	Uncertain	0.851	0.252	0.000											-11.049	Likely Pathogenic	0.374	Ambiguous	Likely Benign	4.17	Destabilizing	0.3	3.77	Destabilizing	3.97	Destabilizing	0.34	Likely Benign	0.734	Likely Pathogenic	-4.47	Deleterious	0.974	Probably Damaging	0.818	Possibly Damaging	-1.48	Pathogenic	0.02	Affected			0.1269	0.3317		-1	-3	4.6	42.08
c.1351C>A	L451I 2D AIThe SynGAP1 L451I missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results come from FoldX, Rosetta, premPS, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta is also inconclusive. Overall, the majority of available predictions (five pathogenic versus four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar record. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000											-11.046	Likely Pathogenic	0.658	Likely Pathogenic	Likely Benign	1.43	Ambiguous	0.8	0.70	Ambiguous	1.07	Ambiguous	0.94	Ambiguous	0.284	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.75	Benign	0.02	Affected			0.0681	0.2958		2	2	0.7	0.00
c.589G>A	E197K 2D AIThe SynGAP1 missense variant E197K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, whereas pathogenic calls arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized. Grouping by consensus, the majority of high‑confidence predictors (AlphaMissense‑Optimized, SGM‑Consensus, PROVEAN, SIFT, ESM1b) indicate pathogenicity, while a minority (REVEL, polyPhen‑2, FATHMM) suggest benign impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, is classified as Likely Pathogenic. AlphaMissense‑Optimized also predicts Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E197K, and this assessment does not conflict with ClinVar, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.349426	Structured	0.431896	Uncertain	0.452	0.492	0.125											-11.045	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-2.50	Deleterious	0.118	Benign	0.037	Benign	4.09	Benign	0.02	Affected			0.1824	0.5890		0	1	-0.4	-0.94
c.1669T>G	S557A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S557A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Optimized and Rosetta, whereas a majority of tools (REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus) predict a pathogenic impact. Uncertain or inconclusive results come from AlphaMissense‑Default, FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.010261	Uncertain	0.924	0.215	0.000											-11.044	Likely Pathogenic	0.421	Ambiguous	Likely Benign	1.26	Ambiguous	0.0	0.09	Likely Benign	0.68	Ambiguous	0.54	Ambiguous	0.801	Likely Pathogenic	-2.70	Deleterious	0.944	Possibly Damaging	0.987	Probably Damaging	-1.69	Pathogenic	0.05	Affected			0.4695	0.4836		1	1	2.6	-16.00
c.454C>G	R152G 2D AIThe SynGAP1 missense variant R152G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R152G is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.043	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-4.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.83	Benign	0.00	Affected			0.3633	0.3956		-3	-2	4.1	-99.14
c.1326A>C	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1326A>T	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.874G>A	A292T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely converge on a deleterious effect: only REVEL classifies it as benign, whereas FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a destabilizing, pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000											-11.039	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.7	3.42	Destabilizing	2.79	Destabilizing	1.08	Destabilizing	0.457	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.68	Pathogenic	0.01	Affected			0.1691	0.7377		1	0	-2.5	30.03
c.523C>G	Q175E 2D AIThe SynGAP1 missense variant Q175E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a benign bias: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, whereas ESM1b predicts it to be pathogenic. AlphaMissense‑Default remains uncertain. High‑accuracy assessment further supports a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta stability analysis is unavailable. Consequently, the overall evidence points to a benign effect for Q175E. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-11.035	Likely Pathogenic	0.502	Ambiguous	Likely Benign										0.149	Likely Benign	-0.68	Neutral	0.118	Benign	0.039	Benign	4.17	Benign	0.40	Tolerated			0.1351	0.2028		2	2	0.0	0.98
c.443C>A	P148H 2D AIThe SynGAP1 missense variant P148H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P148H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-11.034	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-3.21	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.90	Benign	0.00	Affected			0.1881	0.3847		0	-2	-1.6	40.02
c.1471A>G	T491A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T491A is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (gnomAD ID: 6‑33438503‑A‑G). Prediction tools that agree on a benign effect include FoldX, Rosetta, and Foldetta. Tools that predict a pathogenic effect include SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (10 pathogenic vs. 3 benign) indicate a likely pathogenic impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125								6-33438503-A-G	1	6.20e-7	-11.033	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.10	Likely Benign	0.3	-0.27	Likely Benign	-0.09	Likely Benign	1.06	Destabilizing	0.851	Likely Pathogenic	-4.82	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.47	Pathogenic	0.01	Affected	3.37	35	0.3903	0.2874		0	1	2.5	-30.03
c.1571G>A	C524Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while premPS is the sole tool predicting a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-11.032	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.20	Destabilizing	1.4	6.24	Destabilizing	4.72	Destabilizing	0.18	Likely Benign	0.863	Likely Pathogenic	-10.94	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.36	Pathogenic	0.00	Affected			0.1496	0.3911		0	-2	-3.8	60.04
c.676T>C	S226P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S226P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic or likely pathogenic outcome. Uncertain results are reported by FoldX, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Overall, the preponderance of evidence indicates that S226P is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.129801	Structured	0.334959	Uncertain	0.800	0.324	0.250											-11.030	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous	1.51	Ambiguous	1.1	5.29	Destabilizing	3.40	Destabilizing	0.57	Ambiguous	0.776	Likely Pathogenic	-3.22	Deleterious	0.971	Probably Damaging	0.543	Possibly Damaging	5.74	Benign	0.04	Affected			0.2837	0.7038		1	-1	-0.8	10.04
c.3616A>G	K1206E 2D AIThe SynGAP1 missense variant K1206E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas the majority of tools predict a pathogenic impact: polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for K1206E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.025	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-1.87	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.44	Pathogenic	0.02	Affected			0.3247	0.1039		0	1	0.4	0.94
c.1063G>A	G355R 2D AIThe SynGAP1 missense variant G355R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, FoldX, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evaluated tools predict a pathogenic impact, whereas a minority predict benign. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-11.022	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.61	Ambiguous	1.4	0.10	Likely Benign	0.36	Likely Benign	0.60	Ambiguous	0.340	Likely Benign	-6.74	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.80	Pathogenic	0.02	Affected			0.1041	0.4567		-3	-2	-4.1	99.14
c.1063G>C	G355R 2D AIThe SynGAP1 missense variant G355R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, FoldX, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evaluated tools predict a pathogenic impact, whereas a minority predict benign. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-11.022	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.61	Ambiguous	1.4	0.10	Likely Benign	0.36	Likely Benign	0.60	Ambiguous	0.340	Likely Benign	-6.74	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.80	Pathogenic	0.02	Affected			0.1041	0.4567		-3	-2	-4.1	99.14
c.2014A>C	T672P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T672P missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain results come from premPS and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. No predictions are missing or inconclusive. Overall, the majority of evidence points to a pathogenic impact for T672P. This conclusion is not contradicted by ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000											-11.022	Likely Pathogenic	0.346	Ambiguous	Likely Benign	2.22	Destabilizing	0.2	5.54	Destabilizing	3.88	Destabilizing	0.55	Ambiguous	0.087	Likely Benign	-4.20	Deleterious	0.968	Probably Damaging	0.824	Possibly Damaging	3.40	Benign	0.01	Affected			0.1988	0.5532		0	-1	-0.9	-3.99
c.690C>G	C230W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by FATHMM and FoldX, whereas the majority of other in silico predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic impact for C230W, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-11.022	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	-0.21	Likely Benign	0.0	-1.87	Ambiguous	-1.04	Ambiguous	0.74	Ambiguous	0.739	Likely Pathogenic	-8.79	Deleterious	0.983	Probably Damaging	0.841	Possibly Damaging	5.84	Benign	0.01	Affected			0.1589	0.3663		-8	-2	-3.4	83.07
c.542A>T	H181L 2D AIThe SynGAP1 H181L variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans pathogenic (2 pathogenic vs 1 benign). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of standard predictors classify the variant as benign, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500											-11.014	Likely Pathogenic	0.561	Ambiguous	Likely Benign										0.212	Likely Benign	-3.51	Deleterious	0.267	Benign	0.039	Benign	4.17	Benign	0.04	Affected			0.0734	0.4395		-2	-3	7.0	-23.98
c.1078G>C	E360Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and premPS, while a majority of tools predict a pathogenic outcome: SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360Q, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-11.012	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.1	1.38	Ambiguous	0.97	Ambiguous	-0.02	Likely Benign	0.343	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.61	Pathogenic	0.03	Affected			0.1824	0.8282		2	2	0.0	-0.98
c.157G>T	G53W 2D AIThe SynGAP1 missense variant G53W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of available predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-11.012	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.243	Likely Benign	-1.69	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	4.08	Benign	0.00	Affected			0.0678	0.5071		-7	-2	-0.5	129.16
c.1642G>C	E548Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 E548Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Because the predictions are split evenly and the high‑accuracy tools give opposing results, the variant’s functional impact remains ambiguous. Thus, the variant is most likely benign based on the majority of evidence, and this does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-11.006	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	-0.15	Likely Benign	0.0	0.16	Likely Benign	0.01	Likely Benign	0.05	Likely Benign	0.310	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.37	Benign	0.06	Tolerated			0.0957	0.4330		2	2	0.0	-0.98
c.1978A>G	M660V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into three groups: benign predictions come from REVEL, SIFT, and FATHMM; pathogenic predictions arise from SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; the remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evaluated predictors lean toward a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status is available. Thus, based on the current computational evidence, the M660V variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-11.006	Likely Pathogenic	0.836	Likely Pathogenic	Ambiguous	1.83	Ambiguous	0.1	0.77	Ambiguous	1.30	Ambiguous	1.05	Destabilizing	0.419	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.927	Probably Damaging	3.56	Benign	0.13	Tolerated			0.2614	0.2937		2	1	2.3	-32.06
c.2155A>T	N719Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N719Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also uncertain. Overall, the majority of evaluated tools (7 benign vs 4 pathogenic) support a benign classification. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.384043	Structured	0.445381	Uncertain	0.961	0.386	0.000											-11.005	Likely Pathogenic	0.302	Likely Benign	Likely Benign	-0.38	Likely Benign	0.0	-0.62	Ambiguous	-0.50	Ambiguous	0.33	Likely Benign	0.187	Likely Benign	-4.15	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.09	Tolerated			0.0412	0.3951		-2	-2	2.2	49.07
c.620A>C	K207T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K207T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, Foldetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; Foldetta’s stability analysis is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K207T, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-11.002	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.15	Destabilizing	0.8	0.57	Ambiguous	1.36	Ambiguous	0.78	Ambiguous	0.239	Likely Benign	-4.57	Deleterious	0.982	Probably Damaging	0.747	Possibly Damaging	3.99	Benign	0.07	Tolerated			0.1636	0.4031		0	-1	3.2	-27.07
c.1753G>C	A585P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A585P is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools cluster into two groups: the single benign prediction comes from SIFT, while all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic outcome. Based on the convergence of these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-10.999	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	5.44	Destabilizing	0.1	5.92	Destabilizing	5.68	Destabilizing	0.77	Ambiguous	0.549	Likely Pathogenic	-3.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.33	Pathogenic	0.16	Tolerated			0.1884	0.2943		1	-1	-3.4	26.04
c.1871C>T	T624I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T624I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include Rosetta, premPS, and SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for T624I. This prediction is consistent with the lack of ClinVar annotation and does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-10.999	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	-0.74	Ambiguous	0.1	-0.39	Likely Benign	-0.57	Ambiguous	0.14	Likely Benign	0.865	Likely Pathogenic	-5.95	Deleterious	1.000	Probably Damaging	0.972	Probably Damaging	-1.43	Pathogenic	0.08	Tolerated			0.0728	0.4734		0	-1	5.2	12.05
c.2159A>C	D720A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and SIFT, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, whereas Foldetta (combining FoldX‑MD and Rosetta) predicts a benign impact, and AlphaMissense‑Optimized remains uncertain. Overall, the predictions are split, with a slight tilt toward pathogenicity from the consensus and high‑accuracy methods. Thus, the variant is most likely pathogenic based on the available predictions, and this does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-10.999	Likely Pathogenic	0.871	Likely Pathogenic	Ambiguous	-0.14	Likely Benign	0.0	-0.35	Likely Benign	-0.25	Likely Benign	0.40	Likely Benign	0.424	Likely Benign	-6.20	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.16	Pathogenic	0.11	Tolerated			0.3726	0.5551		0	-2	5.3	-44.01
c.1034T>C	L345P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L345P is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-10.994	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.2	3.26	Destabilizing	3.30	Destabilizing	1.27	Destabilizing	0.335	Likely Benign	-4.80	Deleterious	0.998	Probably Damaging	0.889	Possibly Damaging	1.70	Pathogenic	0.02	Affected			0.3581	0.1342		-3	-3	-5.4	-16.04
c.3730A>C	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3732T>A	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3732T>G	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.1624A>C	N542H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542H is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence supports a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-10.983	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.06	Likely Benign	0.1	-0.12	Likely Benign	-0.03	Likely Benign	0.46	Likely Benign	0.791	Likely Pathogenic	-3.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.44	Pathogenic	0.05	Affected			0.1137	0.5368		2	1	0.3	23.04
c.827C>G	P276R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P276R missense variant is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (gnomAD ID 6‑33437732‑C‑G). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Stability‑based predictors (FoldX, Rosetta, premPS, Foldetta) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.037156	Structured	0.338937	Uncertain	0.724	0.230	0.250								6-33437732-C-G	7	4.34e-6	-10.983	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	1.78	Ambiguous	0.2	1.02	Ambiguous	1.40	Ambiguous	0.78	Ambiguous	0.498	Likely Benign	-4.52	Deleterious	0.994	Probably Damaging	0.892	Possibly Damaging	1.89	Pathogenic	0.01	Affected	3.38	19	0.1445	0.2828		-2	0	-2.9	59.07
c.1375G>A	G459S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G459S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL and FATHMM, while pathogenic predictions are made by FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, SGM‑Consensus as Likely Pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-10.979	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	2.34	Destabilizing	0.1	0.77	Ambiguous	1.56	Ambiguous	0.60	Ambiguous	0.414	Likely Benign	-5.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.09	Benign	0.05	Affected			0.2340	0.5197		1	0	-0.4	30.03
c.1535A>C	E512A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show SGM‑Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-10.979	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.97	Ambiguous	0.71	Ambiguous	0.04	Likely Benign	0.309	Likely Benign	-5.71	Deleterious	0.987	Probably Damaging	0.937	Probably Damaging	3.31	Benign	0.12	Tolerated			0.4293	0.5162		0	-1	5.3	-58.04
c.3776T>A	I1259N 2D AIThe SynGAP1 missense variant I1259N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also reports a likely pathogenic classification. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for I1259N. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.979	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.459	Likely Benign	-3.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.51	Benign	0.00	Affected			0.0799	0.0340		-2	-3	-8.0	0.94
c.2104C>G	Q702E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta give uncertain results. High‑accuracy methods further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign; Foldetta remains inconclusive. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-10.974	Likely Pathogenic	0.230	Likely Benign	Likely Benign	0.48	Likely Benign	0.0	0.72	Ambiguous	0.60	Ambiguous	0.27	Likely Benign	0.196	Likely Benign	-2.27	Neutral	0.989	Probably Damaging	0.930	Probably Damaging	3.55	Benign	0.15	Tolerated			0.1021	0.1609		2	2	0.0	0.98
c.1543C>T	R515C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R515C is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (6‑33438786‑C‑T). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact. The remaining tools (FoldX, Rosetta, Foldetta, premPS) give uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.191256	Uncertain	0.924	0.275	0.000								6-33438786-C-T	1	6.20e-7	-10.973	Likely Pathogenic	0.628	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.0	1.13	Ambiguous	1.07	Ambiguous	0.72	Ambiguous	0.691	Likely Pathogenic	-5.49	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.36	Pathogenic	0.01	Affected	3.37	35	0.3055	0.1546		-3	-4	7.0	-53.05
c.3773A>G	Q1258R 2D AIThe SynGAP1 missense variant Q1258R is listed in ClinVar with an uncertain significance (ClinVar ID 3359527.0) and is not observed in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while only REVEL predicts a benign outcome. The high‑accuracy predictors give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available output for this variant. Based on the preponderance of pathogenic predictions and the SGM Consensus, the variant is most likely pathogenic, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250					Uncertain		1				-10.971	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.316	Likely Benign	-3.19	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1027	0.0991		1	1	-1.0	28.06
c.1489T>C	Y497H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497H is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a destabilizing, pathogenic effect. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.393608	Uncertain	0.950	0.181	0.000											-10.970	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	2.46	Destabilizing	0.1	2.40	Destabilizing	2.43	Destabilizing	1.29	Destabilizing	0.819	Likely Pathogenic	-4.94	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.65	Pathogenic	0.02	Affected			0.1983	0.0612		0	2	-1.9	-26.03
c.1233C>G	I411M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411M is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two consensus groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are supported by SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and AlphaMissense‑Optimized yield uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta also predicts pathogenicity. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-10.969	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	1.30	Ambiguous	0.2	2.76	Destabilizing	2.03	Destabilizing	1.21	Destabilizing	0.344	Likely Benign	-2.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.31	Benign	0.00	Affected			0.0677	0.2848		2	1	-2.6	18.03
c.1663G>T	V555F 2D 3DClick to see structure in 3D Viewer AISynGAP1 V555F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.008218	Uncertain	0.943	0.225	0.000											-10.965	Likely Pathogenic	0.599	Likely Pathogenic	Likely Benign	0.17	Likely Benign	0.3	-2.01	Stabilizing	-0.92	Ambiguous	0.16	Likely Benign	0.440	Likely Benign	-2.85	Deleterious	0.011	Benign	0.013	Benign	-1.20	Pathogenic	0.16	Tolerated			0.0727	0.2366		-1	-1	-1.4	48.04
c.1996G>C	E666Q 2D AIThe SynGAP1 E666Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; FoldX is uncertain and therefore not counted. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split and is treated as unavailable. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of reliable predictions indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-10.963	Likely Pathogenic	0.737	Likely Pathogenic	Likely Benign	0.54	Ambiguous	0.5	0.20	Likely Benign	0.37	Likely Benign	0.46	Likely Benign	0.268	Likely Benign	-2.29	Neutral	0.997	Probably Damaging	0.696	Possibly Damaging	3.46	Benign	0.13	Tolerated			0.1437	0.4788		2	2	0.0	-0.98
c.2093A>C	E698A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E698A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or folding result is missing. Overall, the majority of tools (seven versus six) favor a pathogenic interpretation, and this does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-10.962	Likely Pathogenic	0.822	Likely Pathogenic	Ambiguous	0.31	Likely Benign	0.0	0.26	Likely Benign	0.29	Likely Benign	0.25	Likely Benign	0.476	Likely Benign	-5.57	Deleterious	0.997	Probably Damaging	0.991	Probably Damaging	3.35	Benign	0.01	Affected			0.3147	0.4160		0	-1	5.3	-58.04
c.1810T>C	S604P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S604P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include premPS and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy methods give consistent results: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also labels the variant as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. Taken together, the overwhelming majority of computational evidence supports a pathogenic classification for S604P, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.192527	Uncertain	0.911	0.195	0.000											-10.953	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.76	Destabilizing	0.3	8.40	Destabilizing	6.08	Destabilizing	0.04	Likely Benign	0.512	Likely Pathogenic	-4.98	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	3.10	Benign	0.01	Affected			0.2524	0.4829		1	-1	-0.8	10.04
c.1864A>G	T622A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622A is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools with uncertain or inconclusive results—AlphaMissense‑Optimized, Rosetta, Foldetta, and premPS—are treated as unavailable for pathogenicity assessment. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for T622A, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-10.953	Likely Pathogenic	0.827	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	1.04	Ambiguous	0.54	Ambiguous	0.75	Ambiguous	0.893	Likely Pathogenic	-4.58	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.52	Pathogenic	0.01	Affected			0.3191	0.3091		1	0	2.5	-30.03
c.1015A>C	K339Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evaluated tools (8 pathogenic vs. 4 benign) indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-10.952	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	0.06	Likely Benign	0.0	-0.50	Ambiguous	-0.22	Likely Benign	-0.02	Likely Benign	0.458	Likely Benign	-3.06	Deleterious	0.982	Probably Damaging	0.824	Possibly Damaging	1.90	Pathogenic	0.04	Affected			0.4041	0.1012		1	1	0.4	-0.04
c.1256A>C	E419A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-10.951	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.1	0.94	Ambiguous	0.75	Ambiguous	0.28	Likely Benign	0.398	Likely Benign	-5.60	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.32	Benign	0.03	Affected			0.4051	0.6705		0	-1	5.3	-58.04
c.3164G>A	G1055E 2D AIThe SynGAP1 missense variant G1055E is catalogued in gnomAD (variant ID 6‑33443716‑G‑A) but has no ClinVar entry. In silico prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a benign effect. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.982235	Disordered	0.872113	Binding	0.379	0.935	0.875								6-33443716-G-A	1	6.21e-7	-10.951	Likely Pathogenic	0.290	Likely Benign	Likely Benign										0.320	Likely Benign	-0.03	Neutral	0.901	Possibly Damaging	0.456	Possibly Damaging	3.30	Benign	0.10	Tolerated	3.77	5	0.1525	0.4459		-2	0	-3.1	72.06
c.1601C>T	S534F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Tools with uncertain results are AlphaMissense‑Default and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic. Overall, the majority of predictions lean toward a benign effect, and this is consistent with the lack of ClinVar evidence; thus the variant is most likely benign and does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-10.948	Likely Pathogenic	0.492	Ambiguous	Likely Benign	-0.03	Likely Benign	0.1	0.88	Ambiguous	0.43	Likely Benign	0.43	Likely Benign	0.313	Likely Benign	-5.09	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	3.26	Benign	0.00	Affected			0.0621	0.5379		-3	-2	3.6	60.10
c.1688G>A	R563K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R563K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are inconclusive are Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-10.948	Likely Pathogenic	0.335	Likely Benign	Likely Benign	0.25	Likely Benign	0.0	0.66	Ambiguous	0.46	Likely Benign	0.70	Ambiguous	0.198	Likely Benign	-2.37	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	3.46	Benign	0.35	Tolerated			0.4434	0.2379		3	2	0.6	-28.01
c.1270G>T	V424F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V424F is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Optimized) yield uncertain or unavailable results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-10.947	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.99	Ambiguous	0.3	-0.37	Likely Benign	0.81	Ambiguous	0.55	Ambiguous	0.275	Likely Benign	-3.66	Deleterious	0.995	Probably Damaging	0.775	Possibly Damaging	3.40	Benign	0.01	Affected			0.0816	0.2094		-1	-1	-1.4	48.04
c.790C>A	L264I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L264I is not reported in ClinVar and is present in gnomAD (ID 6‑33437695‑C‑A). Prediction tools that indicate a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the balance of evidence—six pathogenic versus three benign predictions, a pathogenic SGM Consensus, and an uncertain Foldetta—suggests that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000								6-33437695-C-A	1	6.20e-7	-10.945	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	1.90	Ambiguous	0.5	0.84	Ambiguous	1.37	Ambiguous	0.95	Ambiguous	0.418	Likely Benign	-1.84	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	0.66	Pathogenic	0.02	Affected	3.38	18	0.0764	0.2630		2	2	0.7	0.00
c.2537T>C	L846S 2D AIThe SynGAP1 missense variant L846S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.944	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-3.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.3128	0.1070		-3	-2	-4.6	-26.08
c.553T>A	S185T 2D AIThe SynGAP1 missense variant S185T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a pathogenic impact. The variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-10.943	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-2.54	Deleterious	0.596	Possibly Damaging	0.142	Benign	3.60	Benign	0.00	Affected			0.1484	0.6236		1	1	0.1	14.03
c.1024T>G	Y342D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y342D is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include premPS and SIFT, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict it to be pathogenic. FoldX reports an uncertain effect, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta is pathogenic. Based on the preponderance of pathogenic predictions and the absence of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250											-10.940	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	1.60	Ambiguous	0.1	2.70	Destabilizing	2.15	Destabilizing	0.13	Likely Benign	0.668	Likely Pathogenic	-7.19	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.71	Pathogenic	0.07	Tolerated			0.3925	0.0862		-4	-3	-2.2	-48.09
c.2517G>C	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2517G>T	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.3661C>T	R1221W 2D AIThe SynGAP1 missense variant R1221W is listed in ClinVar with an uncertain significance (ClinVar ID 1050818.0) and is present in the gnomAD database (gnomAD ID 6‑33446653‑C‑T). Functional prediction tools show a split assessment: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy analyses further refine the picture: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—deems it likely pathogenic. No Foldetta stability assessment is available for this residue. Overall, the majority of computational evidence points toward a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a definitive benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375					Conflicting		3	6-33446653-C-T	1	6.20e-7	-10.938	Likely Pathogenic	0.651	Likely Pathogenic	Likely Benign										0.174	Likely Benign	-4.57	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	2.50	Benign	0.01	Affected	3.77	5	0.1242	0.2585		2	-3	3.6	30.03
c.3779A>T	K1260M 2D AIThe SynGAP1 missense variant K1260M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the substitution as pathogenic. High‑accuracy assessments further support a deleterious impact: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports “Likely Pathogenic”; AlphaMissense‑Optimized yields an uncertain result, and Foldetta’s stability prediction is unavailable. Taken together, the evidence overwhelmingly points to a pathogenic effect for K1260M. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.938	Likely Pathogenic	0.887	Likely Pathogenic	Ambiguous										0.400	Likely Benign	-4.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.0746	0.3366		0	-1	5.8	3.02
c.1267T>A	Y423N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423N is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include SIFT and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-10.937	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.1	4.08	Destabilizing	4.03	Destabilizing	2.07	Destabilizing	0.501	Likely Pathogenic	-7.47	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.06	Tolerated			0.1405	0.0412		-2	-2	-2.2	-49.07
c.548A>G	H183R 2D AIThe SynGAP1 H183R missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus (majority vote) also pathogenic; Foldetta stability analysis is unavailable. Based on the majority of computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.937	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.368	Likely Benign	-5.43	Deleterious	0.596	Possibly Damaging	0.142	Benign	3.90	Benign	0.13	Tolerated			0.1915	0.2249		2	0	-1.3	19.05
c.1283A>C	Y428S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM. All other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-10.936	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	3.00	Destabilizing	0.0	3.42	Destabilizing	3.21	Destabilizing	2.00	Destabilizing	0.505	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.03	Affected			0.4623	0.2352		-3	-2	0.5	-76.10
c.994G>A	D332N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D332N is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, Rosetta, premPS, and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; SGM‑Consensus indicates a likely pathogenic outcome. FoldX and Foldetta give uncertain results. High‑accuracy tools show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, but the high‑accuracy AlphaMissense‑Optimized result is benign and Foldetta is inconclusive. Thus, the variant is most likely pathogenic based on the collective evidence, and this assessment does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-10.931	Likely Pathogenic	0.771	Likely Pathogenic	Likely Benign	1.20	Ambiguous	0.1	-0.16	Likely Benign	0.52	Ambiguous	0.49	Likely Benign	0.396	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.32	Pathogenic	0.11	Tolerated			0.0785	0.3963		2	1	0.0	-0.98
c.536A>T	E179V 2D AIThe SynGAP1 missense variant E179V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-10.930	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-4.34	Deleterious	0.596	Possibly Damaging	0.328	Benign	3.94	Benign	0.01	Affected			0.1077	0.7864		-2	-2	7.7	-29.98
c.1703T>C	V568A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V568A missense variant is not reported in ClinVar (ClinVar status: none) but is present in the gnomAD database (gnomAD ID: 6‑33440755‑T‑C). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the consensus from high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000								6-33440755-T-C	2	1.25e-6	-10.929	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	1.90	Ambiguous	0.1	1.77	Ambiguous	1.84	Ambiguous	2.16	Destabilizing	0.834	Likely Pathogenic	-3.82	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	-1.38	Pathogenic	0.06	Tolerated	3.37	35	0.2413	0.1961		0	0	-2.4	-28.05
c.2107C>T	L703F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta remains unavailable. Overall, the majority of reliable predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.929	Likely Pathogenic	0.768	Likely Pathogenic	Likely Benign	1.03	Ambiguous	0.1	0.59	Ambiguous	0.81	Ambiguous	0.50	Likely Benign	0.247	Likely Benign	-3.25	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.12	Benign	0.00	Affected			0.0600	0.2555		2	0	-1.0	34.02
c.614T>A	I205N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I205N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. No evidence from these tools contradicts the lack of ClinVar annotation. Overall, the majority of predictions (five pathogenic vs. four benign) and the pathogenic SGM Consensus suggest the variant is most likely pathogenic, with no ClinVar status to conflict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.264545	Structured	0.409933	Uncertain	0.821	0.414	0.125											-10.928	Likely Pathogenic	0.552	Ambiguous	Likely Benign	0.66	Ambiguous	0.1	1.16	Ambiguous	0.91	Ambiguous	1.57	Destabilizing	0.138	Likely Benign	-3.56	Deleterious	0.940	Possibly Damaging	0.641	Possibly Damaging	4.06	Benign	0.07	Tolerated			0.0802	0.0212		-2	-3	-8.0	0.94
c.3772C>A	Q1258K 2D AIThe SynGAP1 missense variant Q1258K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify it as pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by seven distinct algorithms. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as likely pathogenic, and Foldetta data are not available. Taken together, the preponderance of evidence from multiple pathogenic predictors and the SGM‑Consensus suggests that the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.927	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.227	Likely Benign	-3.19	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1151	0.2761		1	1	-0.4	0.04
c.754C>T	P252S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P252S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Predictions that are uncertain (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the evidence strongly favors a pathogenic effect for P252S, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-10.926	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.76	Ambiguous	0.1	1.81	Ambiguous	1.29	Ambiguous	0.79	Ambiguous	0.840	Likely Pathogenic	-7.35	Deleterious	0.941	Possibly Damaging	0.531	Possibly Damaging	5.79	Benign	0.05	Affected			0.3508	0.4361		1	-1	0.8	-10.04
c.1976C>T	S659F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659F is listed in ClinVar with an uncertain significance and is absent from gnomAD. Functional prediction tools that provide definitive calls cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, polyPhen2_HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, SGM Consensus predicts pathogenic, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) yields an uncertain result and is therefore unavailable. Overall, the majority of reliable tools favor a pathogenic effect. Thus, the variant is most likely pathogenic, a conclusion that does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000					Uncertain		1				-10.925	Likely Pathogenic	0.662	Likely Pathogenic	Likely Benign	-0.81	Ambiguous	0.1	-0.25	Likely Benign	-0.53	Ambiguous	0.32	Likely Benign	0.194	Likely Benign	-4.59	Deleterious	0.806	Possibly Damaging	0.171	Benign	3.39	Benign	0.05	Affected	3.38	28	0.0897	0.5828		-3	-2	3.6	60.10	221.3	-61.2	0.0	0.0	0.6	0.4						X		Potentially Benign	In the WT simulations, the hydroxyl group of Ser659, located in a kink in the middle of the long α-helix (res. Ser641-Glu666), forms a hydrogen bond with the carboxylate group of Glu656. However, the phenol ring of the Phe659 side chain cannot form a similar hydrogen bond. Instead, it interacts with the hydrophobic isopropyl side chain of Val555 from the opposing α-helix (res. Ala533-Val560). This residue swap may therefore cause issues during protein folding.
c.3605T>A	I1202N 2D AIThe SynGAP1 missense variant I1202N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-10.922	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-5.65	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1014	0.0270		-2	-3	-8.0	0.94
c.2149C>T	L717F 2D AIThe SynGAP1 missense variant L717F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. No folding‑stability metrics (FoldX, Rosetta, premPS) provide decisive evidence. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-10.917	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.6	0.59	Ambiguous	0.67	Ambiguous	0.63	Ambiguous	0.157	Likely Benign	-2.56	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.36	Benign	0.02	Affected			0.0444	0.2207		2	0	-1.0	34.02
c.3597G>C	E1199D 2D AIThe SynGAP1 missense variant E1199D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-10.917	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.234	Likely Benign	-2.08	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.52	Benign	0.00	Affected			0.1728	0.2146		3	2	0.0	-14.03
c.3597G>T	E1199D 2D AIThe SynGAP1 missense variant E1199D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-10.917	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.236	Likely Benign	-2.08	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.52	Benign	0.00	Affected			0.1728	0.2146		3	2	0.0	-14.03
c.601G>T	D201Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D201Y missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, and FATHMM. Those that predict a pathogenic effect comprise SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Rosetta. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM Consensus predicts likely pathogenic; Foldetta is uncertain. Because the majority of consensus and individual predictors (seven pathogenic vs four benign) lean toward a damaging outcome, the variant is most likely pathogenic. This assessment is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.428570	Uncertain	0.698	0.447	0.125											-10.916	Likely Pathogenic	0.892	Likely Pathogenic	Ambiguous	0.28	Likely Benign	0.2	2.39	Destabilizing	1.34	Ambiguous	0.31	Likely Benign	0.334	Likely Benign	-4.93	Deleterious	1.000	Probably Damaging	0.960	Probably Damaging	4.02	Benign	0.02	Affected			0.0431	0.5371		-4	-3	2.2	48.09
c.1508A>C	Q503P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q503P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; the remaining tools (FoldX, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenic. Because the majority of evidence points to a deleterious effect, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.322935	Uncertain	0.848	0.168	0.000											-10.915	Likely Pathogenic	0.414	Ambiguous	Likely Benign	1.06	Ambiguous	0.7	5.94	Destabilizing	3.50	Destabilizing	0.75	Ambiguous	0.860	Likely Pathogenic	-5.20	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	-1.53	Pathogenic	0.03	Affected			0.2076	0.3610		0	-1	1.9	-31.01
c.1209A>C	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1209A>T	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.3778A>G	K1260E 2D AIThe SynGAP1 missense variant K1260E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions point to a pathogenic effect, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.913	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous										0.462	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.3129	0.0877		0	1	0.4	0.94
c.722A>C	K241T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Benign predictions are reported by Rosetta and FATHMM. Two tools (Foldetta and premPS) give uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenic; Foldetta remains uncertain. Overall, the consensus of the majority of evidence points to a pathogenic effect for K241T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.911	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.00	Destabilizing	0.4	0.06	Likely Benign	1.03	Ambiguous	0.60	Ambiguous	0.853	Likely Pathogenic	-5.14	Deleterious	0.995	Probably Damaging	0.747	Possibly Damaging	5.74	Benign	0.03	Affected			0.2021	0.3951		0	-1	3.2	-27.07
c.1441C>T	H481Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H481Y is listed in ClinVar as benign (ClinVar ID 1543764.0) and is present in the gnomAD database (gnomAD ID 6‑33438473‑C‑T). Prediction tools that classify the variant as benign include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta report uncertain stability effects. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Taking all available evidence together, the variant is most likely benign, which is consistent with its ClinVar benign annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000					Likely Benign		1	6-33438473-C-T	16	9.91e-6	-10.910	Likely Pathogenic	0.565	Likely Pathogenic	Likely Benign	-0.53	Ambiguous	0.1	-0.46	Likely Benign	-0.50	Ambiguous	0.20	Likely Benign	0.256	Likely Benign	-3.32	Deleterious	0.988	Probably Damaging	0.979	Probably Damaging	3.40	Benign	0.59	Tolerated	3.37	33	0.0610	0.3558		0	2	1.9	26.03	256.5	-44.4	0.0	0.0	0.2	0.2	X			X				Uncertain	The imidazole ring of the His481 side chain is located in a short helical structure (res. Glu480-Leu482) within an α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. In the WT simulations, His481 alternately stacks against Arg485, Arg587, and Glu480 without a definite role. In the variant simulations, Tyr481 also alternately stacks with nearby arginine residues, including Arg485, Arg587, and Arg479. The interaction between Tyr481 and Arg479 affects the α-α loop, causing it to fold into a distorted helical structure, an effect that might be more pronounced during protein folding. Finally, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.584C>A	A195E 2D AIThe SynGAP1 missense variant A195E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.346032	Structured	0.430388	Uncertain	0.363	0.533	0.125											-10.909	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.237	Likely Benign	-3.20	Deleterious	0.997	Probably Damaging	0.879	Possibly Damaging	4.12	Benign	0.02	Affected			0.0855	0.1877		0	-1	-5.3	58.04
c.646C>A	Q216K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216K is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of tools lean toward a benign classification, but the presence of several pathogenic predictions and a high‑accuracy consensus that is pathogenic introduces uncertainty. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.908	Likely Pathogenic	0.826	Likely Pathogenic	Ambiguous	-0.35	Likely Benign	0.1	0.38	Likely Benign	0.02	Likely Benign	0.17	Likely Benign	0.617	Likely Pathogenic	-2.71	Deleterious	0.779	Possibly Damaging	0.351	Benign	5.92	Benign	0.12	Tolerated			0.2431	0.4591		1	1	-0.4	0.04
c.3355G>T	G1119W 2D AIThe SynGAP1 missense variant G1119W is reported in gnomAD (ID 6‑33443907‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.818538	Binding	0.339	0.928	0.875								6-33443907-G-T			-10.904	Likely Pathogenic	0.336	Likely Benign	Likely Benign										0.386	Likely Benign	-1.19	Neutral	0.997	Probably Damaging	0.949	Probably Damaging	3.90	Benign	0.02	Affected	4.32	2	0.0948	0.4059		-2	-7	-0.5	129.16
c.1774T>G	S592A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S592A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, SIFT, and AlphaMissense‑Optimized, whereas a majority (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.100070	Uncertain	0.913	0.182	0.000											-10.902	Likely Pathogenic	0.572	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.1	-0.93	Ambiguous	-0.71	Ambiguous	0.79	Ambiguous	0.661	Likely Pathogenic	-2.72	Deleterious	0.980	Probably Damaging	0.994	Probably Damaging	-1.25	Pathogenic	0.44	Tolerated			0.4878	0.3318		1	1	2.6	-16.00
c.1010A>C	K337T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, FoldX, and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools report uncertainty: Rosetta, Foldetta, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic. In the high‑accuracy subset, AlphaMissense‑Optimized remains uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta is uncertain. Taken together, the majority of evidence points toward a deleterious effect. Therefore, K337T is most likely pathogenic, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-10.896	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.2	1.33	Ambiguous	0.89	Ambiguous	0.25	Likely Benign	0.338	Likely Benign	-5.32	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.70	Pathogenic	0.01	Affected			0.1741	0.3354		0	-1	3.2	-27.07
c.976C>T	H326Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas a majority of tools (REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for H326Y, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-10.896	Likely Pathogenic	0.855	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.4	0.25	Likely Benign	0.14	Likely Benign	0.07	Likely Benign	0.562	Likely Pathogenic	-5.32	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.92	Pathogenic	0.02	Affected			0.0796	0.4323		0	2	1.9	26.03
c.1359C>A	H453Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H453Q is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, Rosetta, premPS, AlphaMissense‑Optimized, and Foldetta—are treated as unavailable for pathogenicity assessment. High‑accuracy methods specifically show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the preponderance of evidence from consensus and high‑accuracy predictors indicates that H453Q is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-10.894	Likely Pathogenic	0.893	Likely Pathogenic	Ambiguous	0.90	Ambiguous	0.1	1.55	Ambiguous	1.23	Ambiguous	0.92	Ambiguous	0.259	Likely Benign	-7.91	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.09	Tolerated			0.1223	0.3112		3	0	-0.3	-9.01
c.1359C>G	H453Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H453Q is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—are treated as unavailable for pathogenicity assessment. High‑accuracy methods specifically show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for H453Q. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-10.894	Likely Pathogenic	0.893	Likely Pathogenic	Ambiguous	0.90	Ambiguous	0.1	1.55	Ambiguous	1.23	Ambiguous	0.92	Ambiguous	0.258	Likely Benign	-7.91	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.09	Tolerated			0.1223	0.3112		3	0	-0.3	-9.01
c.688T>G	C230G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reached a consensus fall into two groups: benign predictions come from polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or inconclusive results from FoldX, Rosetta, Foldetta, and premPS are treated as unavailable and do not influence the overall assessment. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also Likely Pathogenic; Foldetta remains uncertain. Based on the aggregate predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-10.888	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	0.86	Ambiguous	0.79	Ambiguous	0.81	Ambiguous	0.775	Likely Pathogenic	-9.95	Deleterious	0.001	Benign	0.004	Benign	5.85	Benign	0.03	Affected			0.3313	0.2574		-3	-3	-2.9	-46.09
c.1381G>A	A461T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A461T missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta is also inconclusive. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-10.885	Likely Pathogenic	0.323	Likely Benign	Likely Benign	1.21	Ambiguous	0.2	0.51	Ambiguous	0.86	Ambiguous	0.65	Ambiguous	0.214	Likely Benign	-3.27	Deleterious	0.508	Possibly Damaging	0.042	Benign	3.40	Benign	0.13	Tolerated			0.1083	0.5930		1	0	-2.5	30.03
c.794A>T	K265M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265M missense variant is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify it as damaging. Benign predictions are limited to FoldX, Foldetta, and premPS. Uncertain results come from Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, while Foldetta predicts a benign folding‑stability change. Overall, the preponderance of evidence supports a pathogenic classification for K265M, and this conclusion is not contradicted by the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-10.885	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	-0.22	Likely Benign	0.2	-0.63	Ambiguous	-0.43	Likely Benign	0.19	Likely Benign	0.516	Likely Pathogenic	-3.78	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.1005	0.3695		0	-1	5.8	3.02
c.982T>C	Y328H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y328H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.411940	Structured	0.392519	Uncertain	0.916	0.497	0.000											-10.885	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	2.08	Destabilizing	0.0	2.43	Destabilizing	2.26	Destabilizing	1.35	Destabilizing	0.516	Likely Pathogenic	-4.53	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.54	Pathogenic	0.02	Affected			0.2572	0.0703		0	2	-1.9	-26.03
c.2056G>A	G686S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G686S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Foldetta, SIFT, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is also “Likely Pathogenic.” Uncertain predictions from Rosetta and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta (a combined FoldX‑MD and Rosetta stability method) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-10.884	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.3	0.50	Ambiguous	0.40	Likely Benign	0.69	Ambiguous	0.537	Likely Pathogenic	-5.29	Deleterious	0.998	Probably Damaging	0.929	Probably Damaging	3.46	Benign	0.06	Tolerated			0.2558	0.4355		1	0	-0.4	30.03
c.1369A>C	S457R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S457R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign calls come from REVEL, Rosetta, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenic, whereas Foldetta’s stability analysis is uncertain. Overall, the majority of evidence points toward a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-10.882	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-1.04	Ambiguous	0.0	-0.06	Likely Benign	-0.55	Ambiguous	0.74	Ambiguous	0.468	Likely Benign	-4.47	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.30	Benign	0.05	Affected			0.0781	0.3426		0	-1	-3.7	69.11
c.1371T>A	S457R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S457R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, SGM‑Consensus confirms a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. No other high‑confidence stability predictions are available. Overall, the preponderance of evidence from multiple independent predictors indicates that S457R is most likely pathogenic, and this assessment does not contradict any existing ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-10.882	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-1.04	Ambiguous	0.0	-0.06	Likely Benign	-0.55	Ambiguous	0.74	Ambiguous	0.343	Likely Benign	-4.47	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.30	Benign	0.05	Affected			0.0781	0.3426		0	-1	-3.7	69.11
c.1371T>G	S457R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S457R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, SGM‑Consensus confirms a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. No other high‑confidence stability predictions are available. Overall, the preponderance of evidence from multiple independent predictors indicates that S457R is most likely pathogenic, and this assessment does not contradict any existing ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-10.882	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-1.04	Ambiguous	0.0	-0.06	Likely Benign	-0.55	Ambiguous	0.74	Ambiguous	0.343	Likely Benign	-4.47	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.30	Benign	0.05	Affected			0.0781	0.3426		0	-1	-3.7	69.11
c.766A>T	N256Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include FoldX, Foldetta, premPS, and FATHMM, whereas the majority of tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—label it pathogenic. The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the preponderance of evidence from standard predictors and the two high‑accuracy pathogenic calls suggests that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250											-10.881	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.2	-0.80	Ambiguous	-0.32	Likely Benign	0.30	Likely Benign	0.868	Likely Pathogenic	-6.85	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	5.83	Benign	0.00	Affected			0.0493	0.5881		-2	-2	2.2	49.07
c.1997A>T	E666V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools show mixed results: benign calls come from REVEL, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. FoldX alone is uncertain. Overall, the majority of tools and the high‑accuracy consensus favor a pathogenic interpretation, with no conflict from ClinVar status because no classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-10.870	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.1	0.08	Likely Benign	0.35	Likely Benign	0.31	Likely Benign	0.476	Likely Benign	-5.95	Deleterious	0.575	Possibly Damaging	0.214	Benign	3.44	Benign	0.03	Affected			0.0818	0.5613		-2	-2	7.7	-29.98
c.3707A>C	Q1236P 2D AIThe SynGAP1 missense variant Q1236P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-10.868	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.417	Likely Benign	-3.16	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.65	Benign	0.01	Affected			0.1768	0.3847		0	-1	1.9	-31.01
c.1418T>C	V473A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V473A missense variant is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are all uncertain or unavailable, providing no decisive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of available predictions support a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation (no contradiction). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000											-10.867	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	1.88	Ambiguous	0.0	1.76	Ambiguous	1.82	Ambiguous	2.17	Destabilizing	0.485	Likely Benign	-3.95	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.18	Benign	0.00	Affected			0.2529	0.2521		0	0	-2.4	-28.05
c.3602A>T	E1201V 2D AIThe SynGAP1 missense variant E1201V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple prediction tools and consensus methods indicates that E1201V is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-10.865	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.402	Likely Benign	-5.43	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.0455	0.6308		-2	-2	7.7	-29.98
c.697T>A	C233S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenicity (3 pathogenic vs 1 benign). Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-10.862	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.1	1.25	Ambiguous	0.93	Ambiguous	1.50	Destabilizing	0.764	Likely Pathogenic	-8.89	Deleterious	0.421	Benign	0.080	Benign	5.79	Benign	0.03	Affected			0.4528	0.2833		0	-1	-3.3	-16.06
c.698G>C	C233S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of evidence points to a pathogenic impact for C233S, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-10.862	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.1	1.25	Ambiguous	0.93	Ambiguous	1.50	Destabilizing	0.830	Likely Pathogenic	-8.89	Deleterious	0.421	Benign	0.080	Benign	5.79	Benign	0.03	Affected			0.4528	0.2833		0	-1	-3.3	-16.06
c.1564G>C	E522Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E522Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools show a split: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods reinforce this pattern: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also labels it likely pathogenic, while Foldetta predicts a benign effect on protein stability. Overall, the majority of evidence points to a pathogenic impact. This assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.861	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	-0.13	Likely Benign	0.1	-0.06	Likely Benign	-0.10	Likely Benign	0.03	Likely Benign	0.560	Likely Pathogenic	-2.85	Deleterious	0.992	Probably Damaging	0.993	Probably Damaging	-1.33	Pathogenic	0.07	Tolerated			0.0944	0.4130		2	2	0.0	-0.98
c.703T>G	S235A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S235A has no ClinVar entry and is not present in gnomAD. Prediction tools that indicate benign effects include Rosetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic; Foldetta remains uncertain. Overall, the balance of evidence leans toward a benign interpretation, but the SGM Consensus introduces a pathogenic signal, resulting in a conflicting prediction profile. This assessment does not contradict ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.250310	Structured	0.319150	Uncertain	0.743	0.331	0.000											-10.861	Likely Pathogenic	0.707	Likely Pathogenic	Likely Benign	1.92	Ambiguous	0.1	0.19	Likely Benign	1.06	Ambiguous	0.48	Likely Benign	0.646	Likely Pathogenic	-2.52	Deleterious	0.002	Benign	0.004	Benign	5.49	Benign	0.01	Affected			0.5168	0.4563	Weaken	1	1	2.6	-16.00
c.3595G>A	E1199K 2D AIThe SynGAP1 missense variant E1199K (ClinVar ID 1026146.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33446587‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are not available. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar Uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250					Uncertain		1	6-33446587-G-A	1	6.20e-7	-10.853	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.171	Likely Benign	-2.26	Neutral	1.000	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected	3.77	5	0.1871	0.4072		0	1	-0.4	-0.94
c.1268A>C	Y423S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for Y423S. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-10.847	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	4.28	Destabilizing	0.1	4.78	Destabilizing	4.53	Destabilizing	1.95	Destabilizing	0.345	Likely Benign	-7.39	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.09	Tolerated			0.3152	0.1259		-3	-2	0.5	-76.10
c.782A>G	D261G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D261G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include premPS and FATHMM, while the remaining tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-10.847	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	2.81	Destabilizing	0.5	2.96	Destabilizing	2.89	Destabilizing	0.21	Likely Benign	0.850	Likely Pathogenic	-4.77	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	5.81	Benign	0.02	Affected			0.2924	0.4562		1	-1	3.1	-58.04
c.707C>A	A236E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A236E is not reported in ClinVar and is present in gnomAD (ID 6‑33435558‑C‑A). Functional prediction tools show a split assessment: benign calls come from FATHMM, Rosetta, and the protein‑folding stability method Foldetta; pathogenic calls come from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. When grouped by agreement, the benign‑predicting tools (FATHMM, Rosetta, Foldetta) represent one consensus, while the pathogenic‑predicting tools (REVEL, premPS, PROVEAN, polyPhen‑2, SIFT, ESM1b, AlphaMissense‑Default, SGM‑Consensus) form the opposing consensus. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely pathogenic; Foldetta, combining FoldX‑MD and Rosetta outputs, is benign. Overall, the majority of predictions lean toward pathogenicity, and this does not contradict the ClinVar status, which has no reported classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.185198	Structured	0.329926	Uncertain	0.775	0.330	0.000								6-33435558-C-A	1	6.20e-7	-10.844	Likely Pathogenic	0.835	Likely Pathogenic	Ambiguous	-0.75	Ambiguous	0.2	0.28	Likely Benign	-0.24	Likely Benign	1.08	Destabilizing	0.844	Likely Pathogenic	-4.24	Deleterious	0.998	Probably Damaging	0.900	Possibly Damaging	6.06	Benign	0.02	Affected	3.40	14	0.1075	0.1970		-1	0	-5.3	58.04
c.995A>G	D332G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D332G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Predictions that are inconclusive or uncertain are given by FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for D332G, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-10.844	Likely Pathogenic	0.860	Likely Pathogenic	Ambiguous	1.78	Ambiguous	0.3	0.69	Ambiguous	1.24	Ambiguous	0.63	Ambiguous	0.539	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.31	Pathogenic	0.07	Tolerated			0.3052	0.4765		1	-1	3.1	-58.04
c.1754C>T	A585V 2D AIThe SynGAP1 missense variant A585V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-10.843	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.95	Ambiguous	1.4	1.12	Ambiguous	1.04	Ambiguous	0.51	Ambiguous	0.420	Likely Benign	-3.35	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.27	Pathogenic	0.10	Tolerated			0.1004	0.3496		0	0	2.4	28.05
c.1739G>C	G580A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580A is not reported in ClinVar (ClinVar status: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity are unanimous: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus all predict a deleterious effect. Tools with uncertain or inconclusive results (Rosetta and premPS) are noted as unavailable for pathogenicity inference. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, also classifies the variant as Pathogenic. Consequently, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-10.841	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	2.84	Destabilizing	0.1	1.55	Ambiguous	2.20	Destabilizing	0.64	Ambiguous	0.646	Likely Pathogenic	-5.73	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.22	Pathogenic	0.05	Affected			0.3657	0.2862		1	0	2.2	14.03
c.1838A>C	E613A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E613A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include Rosetta, premPS, and Foldetta, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as benign. Overall, the preponderance of evidence (10 pathogenic vs. 3 benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-10.841	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	0.90	Ambiguous	0.5	-0.17	Likely Benign	0.37	Likely Benign	0.32	Likely Benign	0.688	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.02	Affected			0.4696	0.5929		0	-1	5.3	-58.04
c.1806T>G	I602M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I602M variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. In contrast, the majority of tools predict it to be pathogenic: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show a split: AlphaMissense‑Optimized and Foldetta both predict benign, whereas the SGM‑Consensus predicts pathogenic. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-10.839	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	0.03	Likely Benign	0.1	0.48	Likely Benign	0.26	Likely Benign	1.10	Destabilizing	0.675	Likely Pathogenic	-2.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.97	Pathogenic	0.00	Affected			0.0801	0.2321		2	1	-2.6	18.03
c.1556A>G	E519G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519G missense variant is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; Foldetta is uncertain. Overall, the majority of available predictions (7 pathogenic vs. 4 benign) lean toward a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-10.835	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.22	Likely Benign	0.1	0.92	Ambiguous	0.57	Ambiguous	0.22	Likely Benign	0.458	Likely Benign	-6.12	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.21	Benign	0.01	Affected			0.2729	0.3471		0	-2	3.1	-72.06
c.1976C>A	S659Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659Y is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default; FoldX is uncertain and therefore not considered evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of individual predictors lean toward a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-10.832	Likely Pathogenic	0.600	Likely Pathogenic	Likely Benign	-0.64	Ambiguous	0.1	0.00	Likely Benign	-0.32	Likely Benign	0.29	Likely Benign	0.173	Likely Benign	-4.24	Deleterious	0.084	Benign	0.014	Benign	3.38	Benign	0.04	Affected			0.0993	0.5962		-3	-2	-0.5	76.10
c.1813C>T	P605S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All evaluated in‑silico predictors classify the change as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the unanimous pathogenic predictions, the variant is most likely pathogenic, which contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000					Uncertain		1				-10.830	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.40	Destabilizing	0.1	3.34	Destabilizing	3.37	Destabilizing	1.00	Destabilizing	0.718	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.70	Pathogenic	0.00	Affected	3.37	35	0.3397	0.4676		1	-1	0.8	-10.04	213.8	-15.4	-0.3	0.2	0.2	0.1				X			X	Potentially Pathogenic	Pro605 is located in a short turn between an α helix (res. Glu582-Met603) and a short α helical section (res. Ser606-Phe608). The pyrrolidine side chain of Pro605 packs hydrophobically with nearby hydrophobic residues (e.g., Ile514, Leu623, Leu610) in the inter-helix space. Additionally, proline lacks a free backbone amide group, which breaks the α helix and facilitates the turn in the WT structure.In the variant simulations, the hydroxyl side chain of Ser605 forms hydrogen bonds with the backbone carbonyl groups of Ala601 and Ile602. Importantly, the helix end is more stable than with Pro605 in the WT. Indeed, proline is a more effective secondary structure breaker compared to serine.Thus, the residue swap could have a more profound effect on the actual folding process, for example, by preventing the bending at the α helix end, than what the simulations suggest. Moreover, due to its location at the GAP-Ras interface, the residue swap could affect the GAP-Ras association.
c.1850A>T	E617V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617V has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into benign (premPS, SIFT) and pathogenic (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default). Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic, while AlphaMissense‑Optimized remains uncertain and Foldetta is also uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E617V. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000											-10.826	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.60	Ambiguous	0.1	0.92	Ambiguous	0.76	Ambiguous	0.28	Likely Benign	0.816	Likely Pathogenic	-5.71	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	-1.47	Pathogenic	0.13	Tolerated			0.0587	0.6503		-2	-2	7.7	-29.98
c.419C>T	S140F 2D AIThe SynGAP1 missense variant S140F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) also indicates likely pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for S140F, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-10.824	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.246	Likely Benign	-3.83	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	3.48	Benign	0.00	Affected			0.0565	0.5988		-3	-2	3.6	60.10
c.1768A>T	S590C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S590C has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split assessment: benign predictions come from FoldX, Rosetta, Foldetta, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. The high‑accuracy subset indicates that AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both support a pathogenic or neutral outcome, respectively. Overall, the majority of tools lean toward a pathogenic interpretation, and this aligns with the SGM‑Consensus designation. Because there is no ClinVar classification, the predictions do not contradict existing clinical data. Thus, based on the available computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022667	Structured	0.088943	Uncertain	0.918	0.199	0.000											-10.823	Likely Pathogenic	0.698	Likely Pathogenic	Likely Benign	-0.09	Likely Benign	0.1	0.35	Likely Benign	0.13	Likely Benign	0.56	Ambiguous	0.631	Likely Pathogenic	-4.48	Deleterious	1.000	Probably Damaging	0.968	Probably Damaging	3.08	Benign	0.07	Tolerated			0.1094	0.5332		0	-1	3.3	16.06
c.1076C>A	T359K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T359K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM. The remaining tools—FoldX, Rosetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (seven benign vs. two pathogenic) support a benign classification, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-10.822	Likely Pathogenic	0.517	Ambiguous	Likely Benign	-0.65	Ambiguous	0.1	0.66	Ambiguous	0.01	Likely Benign	0.75	Ambiguous	0.163	Likely Benign	-2.23	Neutral	0.255	Benign	0.045	Benign	1.79	Pathogenic	0.24	Tolerated			0.1618	0.3483		0	-1	-3.2	27.07
c.2839G>T	G947W 2D AIThe SynGAP1 missense variant G947W has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988695	Disordered	0.850554	Binding	0.358	0.919	0.750											-10.819	Likely Pathogenic	0.285	Likely Benign	Likely Benign										0.349	Likely Benign	-1.21	Neutral	0.983	Probably Damaging	0.868	Possibly Damaging	4.90	Benign	0.01	Affected			0.0914	0.4059		-7	-2	-0.5	129.16
c.1289T>A	M430K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and ESM1b. The remaining tools—FoldX, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors a pathogenic outcome; Foldetta remains uncertain. Overall, the majority of individual predictors lean toward a benign interpretation, whereas the SGM Consensus suggests pathogenicity. Given the lack of ClinVar evidence, there is no contradiction with existing clinical annotations. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-10.816	Likely Pathogenic	0.494	Ambiguous	Likely Benign	0.78	Ambiguous	0.1	0.44	Likely Benign	0.61	Ambiguous	0.86	Ambiguous	0.149	Likely Benign	-2.66	Deleterious	0.134	Benign	0.033	Benign	3.47	Benign	0.32	Tolerated			0.1660	0.1271		0	-1	-5.8	-3.02
c.617T>C	I206T 2D AIThe SynGAP1 I206T missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give consistent results: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overall evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not currently listed. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-10.812	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	2.43	Destabilizing	0.5	2.68	Destabilizing	2.56	Destabilizing	1.94	Destabilizing	0.252	Likely Benign	-3.78	Deleterious	0.421	Benign	0.156	Benign	3.65	Benign	0.00	Affected			0.0830	0.0669		0	-1	-5.2	-12.05
c.1598C>A	A533E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000											-10.810	Likely Pathogenic	0.553	Ambiguous	Likely Benign	-0.13	Likely Benign	0.0	-0.26	Likely Benign	-0.20	Likely Benign	0.43	Likely Benign	0.314	Likely Benign	-1.89	Neutral	0.259	Benign	0.107	Benign	-1.18	Pathogenic	0.18	Tolerated			0.1147	0.1498		0	-1	-5.3	58.04
c.1786C>T	R596C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R596C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33440838‑C‑T). Prediction tools that indicate a benign effect include only premPS. All other evaluated algorithms—REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic or likely pathogenic, while Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. **Thus, the variant is most likely pathogenic based on the collective predictions, which does not contradict the ClinVar uncertain status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.017797	Structured	0.135423	Uncertain	0.918	0.134	0.000					Conflicting		2	6-33440838-C-T	6	3.72e-6	-10.805	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	2.94	Destabilizing	0.0	1.49	Ambiguous	2.22	Destabilizing	-0.03	Likely Benign	0.633	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.41	Pathogenic	0.00	Affected	3.37	35	0.3429	0.2211		-4	-3	7.0	-53.05	230.7	97.9	-0.1	0.0	-0.3	0.4		X		X				Potentially Pathogenic	The guanidinium group of Arg596, located in an α helix (res. Glu582-Met603), forms a salt bridge with the carboxylate group of Glu495 from another α helix (res. Leu489-Glu519). In the WT simulations, the side chain of Arg596 hydrogen bonds with the backbone carbonyl groups of Asn487, Glu486, Arg485, and Phe484. Additionally, Arg596 can hydrogen bond with the carboxamide group of the Asn487 side chain on an opposing loop that links two α helices (res. Ala461-Arg475, res. Leu489-Glu519).In the variant simulations, the thiol group of the Cys596 side chain is unable to form salt bridges or any of the hydrogen bonds that the Arg596 side chain can. Thus, the residue swap could affect the tertiary structure assembly more profoundly than observed in the simulations. Notably, Arg596 plays a key role in positioning the aforementioned loop, which is crucial for the placement of the “arginine finger” or the Arg485 side chain during RasGTPase activation.
c.3650A>G	E1217G 2D AIThe SynGAP1 missense variant E1217G is reported in gnomAD (ID 6‑33446642‑A‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1217G. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250								6-33446642-A-G			-10.803	Likely Pathogenic	0.620	Likely Pathogenic	Likely Benign										0.331	Likely Benign	-5.38	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.35	Pathogenic	0.00	Affected	3.77	5	0.2205	0.4927		-2	0	3.1	-72.06
c.3638A>T	N1213I 2D AIThe SynGAP1 missense variant N1213I is not reported in ClinVar and is absent from gnomAD. Prediction tools show a split opinion: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence points to a pathogenic effect for N1213I, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.580690	Disordered	0.521638	Binding	0.888	0.561	0.500											-10.798	Likely Pathogenic	0.743	Likely Pathogenic	Likely Benign										0.093	Likely Benign	-3.10	Deleterious	0.996	Probably Damaging	0.930	Probably Damaging	2.71	Benign	0.03	Affected			0.0437	0.4407		-2	-3	8.0	-0.94
c.1961A>C	E654A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E654A has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Benign. Overall, the balance of evidence favors pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.797	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.1	0.20	Likely Benign	0.35	Likely Benign	0.25	Likely Benign	0.512	Likely Pathogenic	-5.70	Deleterious	0.986	Probably Damaging	0.875	Possibly Damaging	3.34	Benign	0.02	Affected			0.3367	0.3971		0	-1	5.3	-58.04
c.2007T>A	N669K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a Likely Pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-10.797	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.3	1.50	Ambiguous	0.95	Ambiguous	0.94	Ambiguous	0.243	Likely Benign	-5.35	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.03	Affected			0.2647	0.3312		1	0	-0.4	14.07
c.2007T>G	N669K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, FoldX, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus concurs, and the Foldetta stability analysis is inconclusive and therefore not used as evidence. No other tools provide definitive support for benignity. Consequently, the preponderance of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-10.797	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.3	1.50	Ambiguous	0.95	Ambiguous	0.94	Ambiguous	0.243	Likely Benign	-5.35	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.03	Affected			0.2647	0.3312		1	0	-0.4	14.07
c.815G>T	R272L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R272L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and premPS. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the majority of evaluated tools predict a pathogenic impact. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.071867	Structured	0.425620	Uncertain	0.925	0.215	0.125											-10.796	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	1.66	Ambiguous	0.3	-0.46	Likely Benign	0.60	Ambiguous	0.41	Likely Benign	0.470	Likely Benign	-4.57	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.75	Pathogenic	0.01	Affected			0.1691	0.4230		-3	-2	8.3	-43.03
c.2156A>T	N719I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N719I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools report uncertainty: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of predictions lean toward a benign impact, with no conflict with ClinVar status. Thus, the variant is most likely benign based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.384043	Structured	0.445381	Uncertain	0.961	0.386	0.000											-10.794	Likely Pathogenic	0.399	Ambiguous	Likely Benign	-0.19	Likely Benign	0.0	-0.74	Ambiguous	-0.47	Likely Benign	0.40	Likely Benign	0.146	Likely Benign	-4.88	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.71	Benign	0.10	Tolerated			0.0408	0.4493		-2	-3	8.0	-0.94
c.491G>T	R164L 2D AIThe SynGAP1 missense variant R164L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence, including the SGM Consensus, points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for R164L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.512396	Binding	0.317	0.666	0.250											-10.794	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous										0.274	Likely Benign	-3.37	Deleterious	0.001	Benign	0.003	Benign	3.80	Benign	0.00	Affected			0.2137	0.5154		-3	-2	8.3	-43.03
c.2053T>A	L685M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from premPS, Foldetta, Rosetta, and AlphaMissense‑Optimized. High‑accuracy methods give inconclusive results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑to‑2 tie and therefore uncertain; Foldetta also reports an uncertain stability change. Consequently, the overall computational evidence is mixed, with a slight tilt toward pathogenicity. Thus, the variant is most likely pathogenic based on predictions, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-10.790	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	0.35	Likely Benign	0.1	1.01	Ambiguous	0.68	Ambiguous	0.83	Ambiguous	0.281	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.29	Benign	0.01	Affected			0.0814	0.2758		4	2	-1.9	18.03
c.1738G>A	G580S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580S is listed in ClinVar with an “Uncertain” status (ClinVar ID 1487029.0) and is present in the gnomAD database (gnomAD ID 6‑33440790‑G‑A). Among the available in‑silico predictors, the majority (REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) indicate a pathogenic effect, whereas only SIFT predicts a benign outcome. Predictions that are inconclusive or uncertain include Rosetta, Foldetta, premPS, AlphaMissense‑Optimized, and the SGM‑Consensus (which is derived from the pathogenic majority of the four contributing tools). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain (combining a pathogenic FoldX result with an uncertain Rosetta result). Overall, the preponderance of evidence points to a pathogenic effect, which is in contrast to the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000					Uncertain		1	6-33440790-G-A	1	6.20e-7	-10.788	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	2.84	Destabilizing	0.2	0.59	Ambiguous	1.72	Ambiguous	0.87	Ambiguous	0.644	Likely Pathogenic	-5.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.23	Pathogenic	0.07	Tolerated	3.37	34	0.2509	0.3085		1	0	-0.4	30.03	233.9	-49.3	0.8	0.0	0.6	0.1						X		Potentially Benign	Gly580 is located on the outer surface in a short α-α loop turn connecting two α-helices (res. Arg563-Glu578, res. Glu582-Phe608) in the WT simulations. In the variant simulations, the side chain of Ser580 faces outward, and its hydroxyl group does not make any new or additional interactions compared to Gly580 in the WT simulations that could affect the protein structure.
c.1879G>T	A627S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A627S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are Rosetta, PROVEAN, and ESM1b. The remaining tools—FoldX, Foldetta, and premPS—return uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta is uncertain. Overall, the majority of available predictions lean toward a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.100716	Structured	0.037862	Uncertain	0.970	0.210	0.000											-10.782	Likely Pathogenic	0.329	Likely Benign	Likely Benign	1.11	Ambiguous	0.2	2.05	Destabilizing	1.58	Ambiguous	0.71	Ambiguous	0.316	Likely Benign	-2.94	Deleterious	0.411	Benign	0.387	Benign	2.78	Benign	0.11	Tolerated			0.2266	0.4224		1	1	-2.6	16.00
c.1412C>T	S471F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S471F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The remaining tools—AlphaMissense‑Default, FoldX, Rosetta, and Foldetta—return uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. Taken together, the majority of evidence points toward a pathogenic impact for S471F, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.305330	Structured	0.355411	Uncertain	0.888	0.261	0.000											-10.777	Likely Pathogenic	0.492	Ambiguous	Likely Benign	-0.54	Ambiguous	0.1	-1.51	Ambiguous	-1.03	Ambiguous	0.12	Likely Benign	0.423	Likely Benign	-4.75	Deleterious	0.942	Possibly Damaging	0.487	Possibly Damaging	-1.26	Pathogenic	0.02	Affected			0.0553	0.4691		-3	-2	3.6	60.10
c.639C>G	I213M 2D AIThe SynGAP1 missense variant I213M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are PROVEAN and FATHMM, while a larger group—REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) return uncertain or inconclusive results and are therefore treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and Foldetta is uncertain. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.158265	Structured	0.372201	Uncertain	0.850	0.295	0.125											-10.777	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	0.66	Ambiguous	0.5	1.58	Ambiguous	1.12	Ambiguous	0.85	Ambiguous	0.680	Likely Pathogenic	-2.31	Neutral	0.995	Probably Damaging	0.880	Possibly Damaging	5.85	Benign	0.01	Affected			0.0611	0.2524		2	1	-2.6	18.03
c.1544G>A	R515H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R515H is listed in ClinVar with an uncertain significance (ClinVar ID 638438.0) and is present in gnomAD (variant ID 6‑33438787‑G‑A). Prediction tools that agree on a benign effect include AlphaMissense‑Default and AlphaMissense‑Optimized. Those that predict a pathogenic impact comprise REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the balance of evidence favors a pathogenic effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.191256	Uncertain	0.924	0.275	0.000					Uncertain		1	6-33438787-G-A	3	1.86e-6	-10.774	Likely Pathogenic	0.337	Likely Benign	Likely Benign	1.07	Ambiguous	0.2	0.74	Ambiguous	0.91	Ambiguous	1.09	Destabilizing	0.730	Likely Pathogenic	-3.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.32	Pathogenic	0.01	Affected	3.37	35	0.2343	0.0746		2	0	1.3	-19.05	239.2	77.8	0.0	0.0	0.4	0.2		X						Potentially Benign	The guanidinium group of Arg515, located in the middle of an α-helix at the GAP domain (res. Gly502-Tyr518), forms salt bridges with the carboxylate groups of Glu512 on the same helix and Glu217 on a loop in the PH domain. Additionally, the positively charged Arg515 side chain forms hydrogen bonds with Leu610 and Gln612 in an opposing loop (res. Gly609-Asp616). In contrast, in the variant simulations, the imidazole ring of His515 cannot form salt bridges with either of the acidic residues, and its side chain is too short to form hydrogen bonds with the loop residues. Accordingly, the residue swap could weaken the tertiary structure assembly of the protein. Due to the missing N-terminal part of the SynGAP model, the effect could be largely underestimated or missing. Notably, the doubly protonated and positively charged form of histidine was not simulated here.
c.1637G>A	C546Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C546Y is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include FoldX, premPS, and SIFT, whereas the remaining tools—SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic impact. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000											-10.771	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	-0.08	Likely Benign	1.8	4.75	Destabilizing	2.34	Destabilizing	0.09	Likely Benign	0.794	Likely Pathogenic	-8.74	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.07	Pathogenic	0.29	Tolerated			0.1433	0.3015		0	-2	-3.8	60.04
c.1696A>G	K566E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K566E missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Across the evaluated tools, every predictor that returned a definitive call classified the variant as pathogenic: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reported a benign outcome; the only inconclusive result was from Rosetta, which was labeled “Uncertain.” High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta—each returned a pathogenic prediction. Consequently, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-10.759	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.76	Destabilizing	0.2	1.13	Ambiguous	2.45	Destabilizing	1.58	Destabilizing	0.832	Likely Pathogenic	-3.58	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.38	Pathogenic	0.04	Affected			0.3275	0.0850		0	1	0.4	0.94
c.952C>A	P318T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318T is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly favor a deleterious effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenic or likely pathogenic. No tool in the dataset predicts a benign outcome; the only inconclusive results come from Rosetta, Foldetta, and premPS, which are treated as unavailable evidence. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is uncertain. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000											-10.759	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.03	Destabilizing	0.2	1.54	Ambiguous	1.79	Ambiguous	0.84	Ambiguous	0.680	Likely Pathogenic	-7.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.84	Pathogenic	0.01	Affected			0.1583	0.6044		0	-1	0.9	3.99
c.1675T>A	C559S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The remaining tools, premPS and AlphaMissense‑Optimized, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. Based on the overall distribution of predictions, the variant is most likely pathogenic; this conclusion does not contradict the ClinVar status, which has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-10.756	Likely Pathogenic	0.785	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.31	Likely Benign	-0.17	Likely Benign	0.65	Ambiguous	0.450	Likely Benign	-7.26	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.64	Tolerated			0.3940	0.1319		0	-1	-3.3	-16.06
c.1676G>C	C559S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559S has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: premPS (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta) as Benign, and AlphaMissense‑Optimized as Uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-10.756	Likely Pathogenic	0.785	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.31	Likely Benign	-0.17	Likely Benign	0.65	Ambiguous	0.469	Likely Benign	-7.26	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.58	Benign	0.64	Tolerated			0.3940	0.1319		0	-1	-3.3	-16.06
c.599T>C	L200S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L200S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic effect comprise FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). High‑accuracy methods give a pathogenic signal from Foldetta (protein‑folding stability analysis) while AlphaMissense‑Optimized is uncertain and thus not considered evidence. Overall, the majority of available predictions (10 pathogenic vs 4 benign) indicate a pathogenic impact. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125											-10.755	Likely Pathogenic	0.807	Likely Pathogenic	Ambiguous	2.72	Destabilizing	0.1	3.38	Destabilizing	3.05	Destabilizing	1.43	Destabilizing	0.141	Likely Benign	-1.96	Neutral	0.970	Probably Damaging	0.683	Possibly Damaging	4.05	Benign	0.06	Tolerated			0.3279	0.0575		-3	-2	-4.6	-26.08
c.1331A>G	K444R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K444R is not reported in ClinVar and has no gnomAD allele. Prediction tools cluster into benign (REVEL, FoldX, SIFT, FATHMM, AlphaMissense‑Optimized) and pathogenic (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools (Rosetta, premPS) give uncertain results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. No prediction or folding stability result is missing. Overall, six tools favor pathogenicity while five favor benignity, and the high‑accuracy consensus leans toward benign. Thus the variant is most likely pathogenic based on the broader set of predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-10.753	Likely Pathogenic	0.693	Likely Pathogenic	Likely Benign	-0.12	Likely Benign	0.1	-0.61	Ambiguous	-0.37	Likely Benign	0.77	Ambiguous	0.213	Likely Benign	-2.86	Deleterious	0.972	Probably Damaging	0.926	Probably Damaging	3.45	Benign	0.12	Tolerated			0.4597	0.0972		3	2	-0.6	28.01
c.803T>C	I268T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268T is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on pathogenicity include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a destabilizing, pathogenic effect. All available predictions are concordant and point to a deleterious impact. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-10.753	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.44	Destabilizing	0.1	3.19	Destabilizing	3.32	Destabilizing	1.93	Destabilizing	0.828	Likely Pathogenic	-4.24	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.0882	0.0638		0	-1	-5.2	-12.05
c.743G>C	R248P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R248P is listed in ClinVar as Pathogenic (ClinVar ID 1065478.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the overwhelming consensus of pathogenic predictions and the high‑accuracy tool results, the variant is most likely pathogenic, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.267126	Uncertain	0.781	0.346	0.250					Likely Pathogenic		1				-10.751	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.09	Destabilizing	0.6	8.87	Destabilizing	5.98	Destabilizing	1.21	Destabilizing	0.848	Likely Pathogenic	-5.97	Deleterious	0.998	Probably Damaging	0.878	Possibly Damaging	5.64	Benign	0.00	Affected	3.41	14	0.1943	0.4528		0	-2	2.9	-59.07	223.8	126.6	0.0	0.0	-0.2	0.1	X	X						Potentially Pathogenic	The guanidinium group of Arg248, located on an α helix (residues Ala236-Val250), forms two very stable salt bridges with Asp255 (from a short α helical section, res. Lys254-Asn256) and Glu244 (from a nearby loop) in the WT simulations. In the variant simulations, the pyrrolidine side chain of Pro248 cannot form any salt bridges, which could negatively affect the tertiary structure assembly of the PH domain. Additionally, Pro248 lacks a free amide group needed for hydrogen bonding with the backbone carbonyl group of Asn245, disrupting the continuity of the α helix.
c.1091C>A	P364H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P364H is reported in gnomAD (ID 6‑33437996‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic. The protein‑folding stability predictor Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with ClinVar status, which currently lacks an entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437996-C-A			-10.744	Likely Pathogenic	0.632	Likely Pathogenic	Likely Benign	1.65	Ambiguous	0.9	0.25	Likely Benign	0.95	Ambiguous	0.77	Ambiguous	0.407	Likely Benign	-6.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.55	Pathogenic	0.02	Affected	3.39	20	0.1800	0.4584		-2	0	-1.6	40.02
c.2147G>C	R716P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R716P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, premPS, and FATHMM; pathogenic predictions come from AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, Rosetta, Foldetta, and the SGM‑Consensus score. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000											-10.744	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	5.67	Destabilizing	2.93	Destabilizing	0.49	Likely Benign	0.320	Likely Benign	-5.75	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.33	Benign	0.01	Affected			0.2140	0.3576		0	-2	2.9	-59.07
c.1544G>T	R515L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R515L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome; FoldX and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.191256	Uncertain	0.924	0.275	0.000											-10.738	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign	0.71	Ambiguous	0.2	-0.33	Likely Benign	0.19	Likely Benign	0.52	Ambiguous	0.686	Likely Pathogenic	-4.53	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.26	Pathogenic	0.11	Tolerated			0.1666	0.2857		-3	-2	8.3	-43.03
c.1745A>T	E582V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E582V is not reported in ClinVar and is absent from gnomAD. Computational predictors show a split: benign calls from REVEL, Rosetta, premPS, SIFT, and FATHMM; pathogenic calls from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; and two uncertain calls from FoldX and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic consensus: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain due to conflicting inputs. Overall, the computational evidence leans toward pathogenicity, and this assessment does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-10.737	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.87	Ambiguous	0.1	-0.13	Likely Benign	0.37	Likely Benign	0.24	Likely Benign	0.251	Likely Benign	-3.92	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.15	Benign	0.10	Tolerated			0.0564	0.4186		-2	-2	7.7	-29.98
c.1372A>G	T458A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T458A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of reliable predictors (six pathogenic vs. five benign) indicate a pathogenic effect. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-10.734	Likely Pathogenic	0.924	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.0	0.31	Likely Benign	0.34	Likely Benign	0.56	Ambiguous	0.358	Likely Benign	-4.27	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.40	Benign	0.15	Tolerated			0.4137	0.4257		1	0	2.5	-30.03
c.1351C>G	L451V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L451V is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain and does not contribute to the consensus. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; and Foldetta predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for L451V. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000											-10.732	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	2.83	Destabilizing	0.1	1.81	Ambiguous	2.32	Destabilizing	1.39	Destabilizing	0.325	Likely Benign	-2.90	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	2.54	Benign	0.01	Affected			0.1065	0.2856		2	1	0.4	-14.03
c.2164A>C	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools and the high‑accuracy methods lean toward a pathogenic effect. Thus, the variant is most likely pathogenic based on current predictions, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.306	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.2166C>A	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.221	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.2166C>G	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, based on the current computational predictions, the S722R variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.220	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.985C>A	R329S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R329S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) yield uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the majority of available predictions support a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	1.80	Ambiguous	0.3	0.78	Ambiguous	1.29	Ambiguous	0.78	Ambiguous	0.192	Likely Benign	-3.36	Deleterious	0.653	Possibly Damaging	0.226	Benign	4.07	Benign	0.04	Affected			0.2886	0.3625		0	-1	3.7	-69.11
c.745G>C	A249P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A249P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is therefore pathogenic (3 pathogenic vs. 1 benign). High‑accuracy assessments are consistent: AlphaMissense‑Optimized indicates pathogenicity; the SGM‑Consensus (majority vote) is pathogenic; and Foldetta, integrating FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. **Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.505461	Disordered	0.255452	Uncertain	0.810	0.336	0.125											-10.727	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.76	Destabilizing	0.4	8.40	Destabilizing	5.58	Destabilizing	1.04	Destabilizing	0.756	Likely Pathogenic	-3.32	Deleterious	0.176	Benign	0.039	Benign	5.57	Benign	0.03	Affected			0.1429	0.3537		1	-1	-3.4	26.04
c.551A>G	E184G 2D AIThe SynGAP1 missense variant E184G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that E184G is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-10.725	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.353	Likely Benign	-5.52	Deleterious	0.970	Probably Damaging	0.607	Possibly Damaging	3.45	Benign	0.00	Affected			0.3281	0.6534		0	-2	3.1	-72.06
c.170T>C	L57P 2D AIThe SynGAP1 missense variant L57P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-10.724	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-1.77	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.90	Benign	0.00	Affected			0.3651	0.1703		-3	-3	-5.4	-16.04
c.1231A>C	I411L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas a majority (premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Tools with uncertain or mixed outputs are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, yielding no definitive call; and Foldetta also reports an uncertain stability change. Overall, the majority of standard predictors lean toward pathogenicity, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational evidence, though high‑accuracy tools remain inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-10.723	Likely Pathogenic	0.819	Likely Pathogenic	Ambiguous	1.02	Ambiguous	0.3	1.89	Ambiguous	1.46	Ambiguous	1.17	Destabilizing	0.285	Likely Benign	-1.84	Neutral	0.908	Possibly Damaging	0.943	Probably Damaging	3.36	Benign	0.01	Affected			0.0876	0.3539		2	2	-0.7	0.00
c.1388A>G	D463G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Five tools favor pathogenicity versus three favor benign, with the remaining five (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) yielding uncertain results. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, also remains inconclusive. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-10.713	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	0.66	Ambiguous	0.1	1.93	Ambiguous	1.30	Ambiguous	0.54	Ambiguous	0.422	Likely Benign	-6.36	Deleterious	0.994	Probably Damaging	0.824	Possibly Damaging	3.32	Benign	0.09	Tolerated			0.3751	0.4898		1	-1	3.1	-58.04
c.505G>A	D169N 2D AIThe SynGAP1 missense variant D169N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: six methods (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Optimized) predict a benign effect, while three (SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. High‑accuracy assessments are mixed: AlphaMissense‑Optimized indicates benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. No Foldetta stability data are available. Overall, the balance of evidence leans toward a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125					Uncertain		1				-10.713	Likely Pathogenic	0.761	Likely Pathogenic	Likely Benign										0.110	Likely Benign	-2.04	Neutral	0.079	Benign	0.052	Benign	4.07	Benign	0.01	Affected	3.74	4	0.1430	0.7391		2	1	0.0	-0.98
c.1201C>T	R401W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401W is listed in gnomAD (ID 6‑33438106‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions are returned by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Only FATHMM predicts a benign outcome; all other tools are either pathogenic or inconclusive. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. Taken together, the overwhelming majority of predictions support a pathogenic effect, and this conclusion is not contradicted by ClinVar data, which currently contains no classification for the variant. Based on the aggregate predictions, the variant is most likely pathogenic, and this is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000								6-33438106-C-T	2	1.24e-6	-10.712	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.59	Ambiguous	0.2	1.04	Ambiguous	1.32	Ambiguous	0.73	Ambiguous	0.711	Likely Pathogenic	-7.34	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	5.40	Benign	0.00	Affected	3.38	27	0.1252	0.3791		-3	2	3.6	30.03
c.948C>A	N316K 2D AIThe SynGAP1 missense variant N316K is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic outcome: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. No other high‑confidence predictions are available. Overall, the preponderance of evidence points to a pathogenic effect for N316K, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-10.711	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.52	Ambiguous	0.7	0.86	Ambiguous	0.69	Ambiguous	0.67	Ambiguous	0.254	Likely Benign	-3.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.77	Pathogenic	0.13	Tolerated			0.2220	0.6593		1	0	-0.4	14.07
c.948C>G	N316K 2D AISynGAP1 missense variant N316K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict pathogenicity: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of computational predictions indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-10.711	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.52	Ambiguous	0.7	0.86	Ambiguous	0.69	Ambiguous	0.67	Ambiguous	0.254	Likely Benign	-3.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.77	Pathogenic	0.13	Tolerated			0.2220	0.6593		1	0	-0.4	14.07
c.1027G>T	V343F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and premPS, whereas pathogenic predictions are made by SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. No evidence from FoldX or Rosetta alone is available. Overall, the majority of predictions support a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250											-10.709	Likely Pathogenic	0.799	Likely Pathogenic	Ambiguous	1.51	Ambiguous	0.4	1.28	Ambiguous	1.40	Ambiguous	0.23	Likely Benign	0.324	Likely Benign	-3.37	Deleterious	0.976	Probably Damaging	0.759	Possibly Damaging	1.61	Pathogenic	0.01	Affected			0.0915	0.4552		-1	-1	-1.4	48.04
c.1274C>A	T425N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, FoldX, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions labeled uncertain (Foldetta, premPS, AlphaMissense‑Optimized, Rosetta) are treated as unavailable. High‑accuracy assessments further indicate a likely pathogenic outcome from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and an uncertain result from AlphaMissense‑Optimized and Foldetta. Overall, the majority of definitive predictions support a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-10.709	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.1	0.81	Ambiguous	0.50	Ambiguous	0.82	Ambiguous	0.185	Likely Benign	-3.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.44	Benign	0.04	Affected			0.1169	0.2843		0	0	-2.8	13.00
c.487T>A	F163I 2D AIThe SynGAP1 missense variant F163I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (five pathogenic vs. three benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-10.706	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-1.62	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	4.12	Benign	0.03	Affected			0.2114	0.2320		1	0	1.7	-34.02
c.1849G>A	E617K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617K is not reported in ClinVar but is present in gnomAD (6‑33440901‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from FoldX, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. A third set of methods (Foldetta, AlphaMissense‑Optimized, Rosetta) yield uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect for E617K, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000								6-33440901-G-A	1	6.20e-7	-10.702	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	0.37	Likely Benign	0.1	1.19	Ambiguous	0.78	Ambiguous	0.17	Likely Benign	0.534	Likely Pathogenic	-3.32	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	-1.34	Pathogenic	0.48	Tolerated	3.37	35	0.1981	0.6282		1	0	-0.4	-0.94
c.1420G>A	D474N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474N missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further indicate that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. AlphaMissense‑Optimized is inconclusive and therefore not considered evidence. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-10.696	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous	0.13	Likely Benign	0.0	0.31	Likely Benign	0.22	Likely Benign	0.06	Likely Benign	0.542	Likely Pathogenic	-4.21	Deleterious	0.992	Probably Damaging	0.990	Probably Damaging	-1.18	Pathogenic	0.08	Tolerated			0.1047	0.4135		2	1	0.0	-0.98
c.1876A>C	I626L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I626L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default predict a pathogenic outcome. Three tools—Foldetta, premPS, and Rosetta—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta also yields an uncertain stability prediction. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-10.696	Likely Pathogenic	0.622	Likely Pathogenic	Likely Benign	0.32	Likely Benign	0.1	1.00	Ambiguous	0.66	Ambiguous	0.83	Ambiguous	0.311	Likely Benign	-1.86	Neutral	0.955	Possibly Damaging	0.985	Probably Damaging	3.52	Benign	0.12	Tolerated			0.0741	0.2461		2	2	-0.7	0.00
c.1448T>C	I483T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.415850	Uncertain	0.798	0.254	0.000											-10.692	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.32	Destabilizing	0.0	2.05	Destabilizing	2.19	Destabilizing	1.77	Destabilizing	0.474	Likely Benign	-4.24	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.15	Benign	0.05	Affected			0.0888	0.0840		0	-1	-5.2	-12.05
c.1549C>G	L517V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the change is deleterious: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while benign predictions are made by SIFT and AlphaMissense‑Optimized; the remaining tools (Rosetta, Foldetta, AlphaMissense‑Default) are uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the preponderance of evidence points to a likely pathogenic effect of the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-10.691	Likely Pathogenic	0.498	Ambiguous	Likely Benign	2.04	Destabilizing	0.3	1.37	Ambiguous	1.71	Ambiguous	1.14	Destabilizing	0.577	Likely Pathogenic	-2.68	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.26	Pathogenic	0.17	Tolerated			0.1405	0.2398		2	1	0.4	-14.03
c.2147G>T	R716L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R716L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, premPS, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (7/13) lean toward pathogenicity, with a near‑even split and a slight edge for pathogenic. The variant is therefore most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists for R716L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000											-10.690	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign	0.31	Likely Benign	0.0	0.51	Ambiguous	0.41	Likely Benign	0.37	Likely Benign	0.289	Likely Benign	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.46	Benign	0.01	Affected			0.1701	0.3775		-3	-2	8.3	-43.03
c.2789C>T	P930L 2D AIThe SynGAP1 missense variant P930L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P930L, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-10.690	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.440	Likely Benign	-7.25	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.2275	0.6113		-3	-3	5.4	16.04
c.3694A>G	K1232E 2D AIThe SynGAP1 missense variant K1232E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-10.690	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.2965	0.1039		0	1	0.4	0.94
c.1901C>G	A634G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A634G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls are made by Rosetta, premPS, PROVEAN, both polyPhen‑2 versions, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta give uncertain results. High‑accuracy assessments indicate AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta remains uncertain. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy consensus also supports a pathogenic interpretation. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-10.685	Likely Pathogenic	0.613	Likely Pathogenic	Likely Benign	1.63	Ambiguous	0.1	2.27	Destabilizing	1.95	Ambiguous	1.09	Destabilizing	0.418	Likely Benign	-3.98	Deleterious	0.997	Probably Damaging	0.990	Probably Damaging	2.69	Benign	0.15	Tolerated			0.2182	0.3187		1	0	-2.2	-14.03
c.1521G>C	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas a pathogenic signal is reported by REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta’s stability prediction is unavailable. Overall, the majority of tools (10 out of 14 with definitive calls) predict a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1521G>T	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, while those that predict a pathogenic effect comprise REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (10 pathogenic vs. 4 benign) predict a deleterious impact. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.2001C>G	I667M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I667M is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy methods give AlphaMissense‑Optimized a benign prediction, SGM‑Consensus a pathogenic prediction (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta an uncertain result. Overall, the majority of evidence—including the high‑accuracy consensus—points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-10.679	Likely Pathogenic	0.579	Likely Pathogenic	Likely Benign	1.29	Ambiguous	0.3	1.68	Ambiguous	1.49	Ambiguous	0.92	Ambiguous	0.360	Likely Benign	-2.90	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	2.98	Benign	0.00	Affected			0.0746	0.2612		2	1	-2.6	18.03
c.1082A>T	Q361L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8 benign vs 5 pathogenic) favor a benign effect, and this consensus does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-10.678	Likely Pathogenic	0.238	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.46	Likely Benign	0.29	Likely Benign	0.21	Likely Benign	0.406	Likely Benign	-3.95	Deleterious	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.06	Tolerated			0.0720	0.5213		-2	-2	7.3	-14.97
c.752A>T	K251M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K251M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, PROVEAN, and FATHMM. Those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect. Overall, the evidence is evenly split between benign and pathogenic predictions, with the most reliable high‑accuracy tools leaning toward a benign outcome. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-10.678	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	0.14	Likely Benign	0.1	0.10	Likely Benign	0.12	Likely Benign	0.05	Likely Benign	0.751	Likely Pathogenic	-2.36	Neutral	0.999	Probably Damaging	0.970	Probably Damaging	5.73	Benign	0.05	Affected			0.1271	0.3475		0	-1	5.8	3.02
c.1537T>G	F513V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.675	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.54	Destabilizing	0.4	2.68	Destabilizing	3.11	Destabilizing	1.13	Destabilizing	0.799	Likely Pathogenic	-6.70	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.44	Tolerated			0.1656	0.1583		-1	-1	1.4	-48.04
c.1547C>G	A516G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A516G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are limited to SIFT, whereas the remaining seven tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) all predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No stability‑change predictions are definitive. Overall, the majority of evidence points to a pathogenic impact for A516G. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-10.673	Likely Pathogenic	0.864	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.2	1.12	Ambiguous	0.99	Ambiguous	0.88	Ambiguous	0.557	Likely Pathogenic	-3.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.31	Pathogenic	0.10	Tolerated			0.2379	0.4370		1	0	-2.2	-14.03
c.1285C>T	R429W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429W is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438190‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; premPS and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000					Conflicting		5	6-33438190-C-T	65	4.03e-5	-10.666	Likely Pathogenic	0.500	Ambiguous	Likely Benign	0.31	Likely Benign	0.1	-0.13	Likely Benign	0.09	Likely Benign	0.52	Ambiguous	0.282	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.41	Benign	0.03	Affected	3.38	25	0.1232	0.3422		2	-3	3.6	30.03	252.3	45.5	0.0	0.0	0.2	0.1		X						Potentially Pathogenic	The guanidinium group of Arg429, located in an α helix (res. Met414-Glu436), either forms a salt bridge with the carboxylate group of an acidic residue (Asp474, Asp467) or a H-bond with the hydroxyl group of Ser471 in an opposing α helix (res. Ala461-Phe476). In the variant simulations, the indole ring of the Trp429 side chain cannot form ionic interactions with the acidic residues. Although it forms a H-bond with Ser471, the bonding is not as strong as that of arginine. The residue swap could affect the tertiary structure assembly during folding; however, no large-scale negative effects were seen during the simulations.
c.3775A>T	I1259F 2D AIThe SynGAP1 missense variant I1259F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized returns an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign) points toward a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.666	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-1.68	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.55	Benign	0.03	Affected			0.0428	0.2563		1	0	-1.7	34.02
c.2026A>C	S676R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, FATHMM, and polyPhen‑2 HumVar, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing; all available data are reported. Overall, the balance of evidence (six benign versus four pathogenic predictions, with the high‑accuracy Foldetta supporting benign) indicates that the variant is most likely benign. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-10.665	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	0.22	Likely Benign	0.3	0.74	Ambiguous	0.48	Likely Benign	0.45	Likely Benign	0.136	Likely Benign	-2.34	Neutral	0.891	Possibly Damaging	0.278	Benign	3.40	Benign	0.02	Affected			0.0962	0.3454		0	-1	-3.7	69.11
c.2028C>A	S676R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, FATHMM, and polyPhen‑2 HumVar, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing; all available data are included. Overall, the balance of evidence (six benign versus four pathogenic predictions, with the high‑accuracy Foldetta supporting benign) indicates that the variant is most likely benign. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-10.665	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	0.22	Likely Benign	0.3	0.74	Ambiguous	0.48	Likely Benign	0.45	Likely Benign	0.157	Likely Benign	-2.34	Neutral	0.891	Possibly Damaging	0.278	Benign	3.40	Benign	0.02	Affected			0.0962	0.3454		0	-1	-3.7	69.11
c.2028C>G	S676R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, FATHMM, and polyPhen‑2 HumVar, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing; all available data are included. Overall, the balance of evidence (six benign versus four pathogenic predictions, with the high‑accuracy Foldetta supporting benign) indicates that the variant is most likely benign. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-10.665	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	0.22	Likely Benign	0.3	0.74	Ambiguous	0.48	Likely Benign	0.45	Likely Benign	0.156	Likely Benign	-2.34	Neutral	0.891	Possibly Damaging	0.278	Benign	3.40	Benign	0.02	Affected			0.0962	0.3454		0	-1	-3.7	69.11
c.1381G>T	A461S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv), SIFT, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta’s stability analysis is also unavailable. Overall, the balance of evidence leans toward a benign effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-10.663	Likely Pathogenic	0.309	Likely Benign	Likely Benign	0.87	Ambiguous	0.0	1.18	Ambiguous	1.03	Ambiguous	0.63	Ambiguous	0.236	Likely Benign	-2.74	Deleterious	0.600	Possibly Damaging	0.289	Benign	3.36	Benign	0.02	Affected			0.2401	0.4551		1	1	-2.6	16.00
c.608A>T	D203V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools and the SGM Consensus lean toward a pathogenic interpretation, whereas two high‑accuracy methods (AlphaMissense‑Optimized and Foldetta) suggest benign. Because ClinVar contains no entry for this variant, there is no contradiction between the predictions and existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-10.660	Likely Pathogenic	0.523	Ambiguous	Likely Benign	0.32	Likely Benign	0.0	0.44	Likely Benign	0.38	Likely Benign	0.05	Likely Benign	0.289	Likely Benign	-4.07	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	3.98	Benign	0.02	Affected			0.0534	0.4084		-2	-3	7.7	-15.96
c.2086C>A	L696I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696I missense change is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is unavailable. Overall, the majority of conventional tools lean toward pathogenicity, and the high‑accuracy prediction that is available (AlphaMissense‑Optimized) indicates benign, leaving the evidence mixed. Thus, the variant is most likely pathogenic based on the preponderance of predictions, and this does not contradict the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-10.652	Likely Pathogenic	0.698	Likely Pathogenic	Likely Benign	1.01	Ambiguous	0.1	0.58	Ambiguous	0.80	Ambiguous	0.85	Ambiguous	0.250	Likely Benign	-1.86	Neutral	0.996	Probably Damaging	0.989	Probably Damaging	3.15	Benign	0.00	Affected			0.0921	0.2542		2	2	0.7	0.00
c.2069C>G	S690C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690C is not reported in ClinVar and has no gnomAD entry. Consensus predictions from high‑accuracy tools show a split: AlphaMissense‑Optimized rates it benign, whereas the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, also predicts a benign effect. In contrast, the broader set of in silico predictors is divided: benign calls come from REVEL, FoldX, Rosetta, Foldetta, and FATHMM; pathogenic calls arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The premPS score is uncertain. Overall, the majority of tools (seven pathogenic vs. six benign) lean toward a pathogenic interpretation, but the presence of strong benign evidence from several high‑confidence methods tempers this conclusion. Thus, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-10.651	Likely Pathogenic	0.749	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.0	0.40	Likely Benign	0.33	Likely Benign	0.82	Ambiguous	0.358	Likely Benign	-4.69	Deleterious	0.999	Probably Damaging	0.944	Probably Damaging	3.33	Benign	0.00	Affected			0.0787	0.4612		0	-1	3.3	16.06
c.847G>C	E283Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The premPS score is uncertain and does not contribute to the consensus. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of tools (nine pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-10.650	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.48	Likely Benign	0.1	-0.01	Likely Benign	0.24	Likely Benign	0.61	Ambiguous	0.372	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.67	Pathogenic	0.01	Affected			0.1432	0.5389		2	2	0.0	-0.98
c.1792C>T	L598F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L598F is not reported in ClinVar and is absent from gnomAD. Computational predictors show mixed results: benign calls come from REVEL, Rosetta, premPS, SIFT, and FATHMM; pathogenic calls come from SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX and AlphaMissense‑Optimized returned uncertain results, which are treated as unavailable evidence. High‑accuracy tools give a split view: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the balance of evidence leans toward pathogenicity, with six pathogenic versus five benign predictions and no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-10.649	Likely Pathogenic	0.820	Likely Pathogenic	Ambiguous	1.12	Ambiguous	0.7	-0.24	Likely Benign	0.44	Likely Benign	0.47	Likely Benign	0.283	Likely Benign	-3.91	Deleterious	0.999	Probably Damaging	0.946	Probably Damaging	3.62	Benign	0.22	Tolerated			0.0630	0.1414		2	0	-1.0	34.02
c.839A>G	Y280C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions are absent; all evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the change as pathogenic or likely pathogenic. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely pathogenic verdict, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a pathogenic effect on protein stability. Consequently, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125											-10.645	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.85	Destabilizing	0.2	4.45	Destabilizing	4.15	Destabilizing	1.68	Destabilizing	0.629	Likely Pathogenic	-8.24	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.96	Pathogenic	0.01	Affected			0.2877	0.1296		0	-2	3.8	-60.04
c.406C>G	R136G 2D AIThe SynGAP1 missense variant R136G is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls arise from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.433034	Structured	0.657394	Binding	0.351	0.894	0.250											-10.641	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.246	Likely Benign	-3.46	Deleterious	0.487	Possibly Damaging	0.211	Benign	3.47	Benign	0.00	Affected			0.3581	0.3585		-3	-2	4.1	-99.14
c.767A>G	N256S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256S is listed in ClinVar as Pathogenic (ClinVar ID 2584352.0) and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic calls come from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy subset gives AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions support a pathogenic effect, aligning with the ClinVar classification. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250					Likely Pathogenic		1				-10.640	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.31	Likely Benign	0.2	0.36	Likely Benign	0.34	Likely Benign	0.48	Likely Benign	0.707	Likely Pathogenic	-4.33	Deleterious	0.997	Probably Damaging	0.970	Probably Damaging	5.87	Benign	0.02	Affected	3.39	15	0.3024	0.5864		1	1	2.7	-27.03
c.1013A>C	D338A 2D 3DClick to see structure in 3D Viewer AISynGAP1 D338A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, polyPhen‑2 HumVar, and SIFT, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-10.639	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	1.22	Ambiguous	0.3	1.11	Ambiguous	1.17	Ambiguous	0.16	Likely Benign	0.479	Likely Benign	-5.74	Deleterious	0.625	Possibly Damaging	0.192	Benign	1.73	Pathogenic	0.11	Tolerated			0.3830	0.5988		0	-2	5.3	-44.01
c.1072T>A	F358I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F358I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports an uncertain impact. Overall, the preponderance of evidence points to a pathogenic effect for F358I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-10.636	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.2	1.66	Ambiguous	1.30	Ambiguous	0.95	Ambiguous	0.393	Likely Benign	-4.45	Deleterious	0.993	Probably Damaging	0.977	Probably Damaging	4.07	Benign	0.13	Tolerated			0.2331	0.2821		1	0	1.7	-34.02
c.1289T>G	M430R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and ESM1b. The remaining tools—FoldX, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of consensus tools lean toward a benign classification, while a subset of high‑accuracy methods suggest pathogenicity, leaving the variant’s impact ambiguous. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-10.636	Likely Pathogenic	0.558	Ambiguous	Likely Benign	0.98	Ambiguous	0.1	0.47	Likely Benign	0.73	Ambiguous	0.83	Ambiguous	0.153	Likely Benign	-2.87	Deleterious	0.620	Possibly Damaging	0.046	Benign	3.48	Benign	0.38	Tolerated			0.1775	0.1652		0	-1	-6.4	24.99
c.2024A>C	N675T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Uncertain results come from Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. No evidence contradicts the ClinVar status. Overall, the balance of evidence, especially from the high‑accuracy tools, indicates that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-10.636	Likely Pathogenic	0.208	Likely Benign	Likely Benign	0.36	Likely Benign	0.3	-0.67	Ambiguous	-0.16	Likely Benign	0.56	Ambiguous	0.258	Likely Benign	-4.63	Deleterious	0.991	Probably Damaging	0.710	Possibly Damaging	3.49	Benign	0.05	Affected			0.1283	0.7910		0	0	2.8	-13.00
c.1801G>A	A601T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A601T missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized, whereas the remaining pathogenic‑predicting tools—SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently flag the variant as deleterious. Two tools, FoldX and premPS, return uncertain results and are not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000											-10.635	Likely Pathogenic	0.662	Likely Pathogenic	Likely Benign	1.55	Ambiguous	0.1	2.66	Destabilizing	2.11	Destabilizing	0.76	Ambiguous	0.642	Likely Pathogenic	-3.98	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	2.57	Benign	0.00	Affected			0.1564	0.5554		1	0	-2.5	30.03
c.2515A>C	K839Q 2D AIThe SynGAP1 missense variant K839Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions and the consensus call indicate a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.631	Likely Pathogenic	0.694	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-1.98	Neutral	0.972	Probably Damaging	0.862	Possibly Damaging	2.47	Pathogenic	0.02	Affected			0.4544	0.1437		1	1	0.4	-0.04
c.1933T>C	F645L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX, Rosetta, or premPS is available to alter this view. Overall, the majority of computational evidence points to a pathogenic impact for F645L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-10.624	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	1.25	Ambiguous	1.12	Ambiguous	0.99	Ambiguous	0.264	Likely Benign	-4.24	Deleterious	0.116	Benign	0.008	Benign	3.44	Benign	0.03	Affected			0.2214	0.3873		2	0	1.0	-34.02
c.1935T>A	F645L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX, Rosetta, or premPS is available to alter this view. Overall, the majority of computational evidence points to a pathogenic impact for F645L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-10.624	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	1.25	Ambiguous	1.12	Ambiguous	0.99	Ambiguous	0.159	Likely Benign	-4.24	Deleterious	0.116	Benign	0.008	Benign	3.44	Benign	0.03	Affected			0.2214	0.3873		2	0	1.0	-34.02
c.1935T>G	F645L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess sequence conservation and structural impact fall into two groups: benign predictions are made by REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM; pathogenic predictions are made by SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. No evidence from FoldX‑MD, Rosetta, or premPS is available to alter this conclusion. Overall, the majority of computational evidence points to a pathogenic impact for F645L, and this assessment is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-10.624	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	1.25	Ambiguous	1.12	Ambiguous	0.99	Ambiguous	0.159	Likely Benign	-4.24	Deleterious	0.116	Benign	0.008	Benign	3.44	Benign	0.03	Affected			0.2214	0.3873		2	0	1.0	-34.02
c.790C>G	L264V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L264V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized; all other evaluated algorithms (SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic or likely pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as Pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for L264V, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000											-10.621	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	2.55	Destabilizing	0.1	1.62	Ambiguous	2.09	Destabilizing	1.24	Destabilizing	0.444	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	0.73	Pathogenic	0.01	Affected			0.1280	0.2289		2	1	0.4	-14.03
c.1091C>T	P364L 2D 3DClick to see structure in 3D Viewer AISynGAP1 P364L is reported in gnomAD (ID 6‑33437996‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, AlphaMissense‑Optimized, and Foldetta; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Three tools—FoldX, Rosetta, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the balance of evidence slightly favors a benign effect, and this conclusion does not contradict any ClinVar classification because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437996-C-T			-10.620	Likely Pathogenic	0.457	Ambiguous	Likely Benign	0.88	Ambiguous	0.9	-0.73	Ambiguous	0.08	Likely Benign	0.31	Likely Benign	0.387	Likely Benign	-7.78	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.54	Pathogenic	0.18	Tolerated	3.39	20	0.2200	0.6207		-3	-3	5.4	16.04
c.1553A>T	Y518F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518F missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools are uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of individual predictors (seven benign vs. four pathogenic) support a benign classification, and this does not contradict the ClinVar status, which has no entry for this variant. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-10.617	Likely Pathogenic	0.466	Ambiguous	Likely Benign	0.34	Likely Benign	0.1	-0.61	Ambiguous	-0.14	Likely Benign	0.41	Likely Benign	0.318	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.22	Tolerated			0.2107	0.2230		7	3	4.1	-16.00
c.2093A>G	E698G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E698G missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all indicate deleteriousness. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive, providing no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E698G. This prediction aligns with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-10.617	Likely Pathogenic	0.786	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.0	1.25	Ambiguous	0.91	Ambiguous	0.29	Likely Benign	0.439	Likely Benign	-6.37	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.31	Benign	0.01	Affected			0.2529	0.3286		0	-2	3.1	-72.06
c.1543C>A	R515S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R515S missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on benign impact include only SIFT, while the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the four pathogenic‑predicted tools) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Other stability‑based predictions (FoldX, Rosetta, premPS) are also uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.191256	Uncertain	0.924	0.275	0.000											-10.615	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	1.54	Ambiguous	0.3	1.11	Ambiguous	1.33	Ambiguous	0.92	Ambiguous	0.586	Likely Pathogenic	-3.03	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.28	Pathogenic	0.17	Tolerated			0.2707	0.1849		0	-1	3.7	-69.11
c.554C>G	S185C 2D AIThe SynGAP1 missense variant S185C has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (derived from the same set of predictors) also reports likely pathogenic. Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-10.612	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.266	Likely Benign	-3.96	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.54	Benign	0.00	Affected			0.0989	0.6000		0	-1	3.3	16.06
c.834G>C	K278N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the majority of tools support a pathogenic effect, so the variant is most likely pathogenic; this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.834G>T	K278N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K278N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas tools that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With a majority of evidence pointing to deleterious effects and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.2083C>G	L695V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta is also unavailable. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-10.605	Likely Pathogenic	0.317	Likely Benign	Likely Benign	1.61	Ambiguous	0.0	1.57	Ambiguous	1.59	Ambiguous	1.19	Destabilizing	0.274	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.20	Benign	0.02	Affected			0.1158	0.2828		2	1	0.4	-14.03
c.3625C>A	L1209M 2D AIThe SynGAP1 missense variant L1209M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL and PROVEAN; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized remains uncertain, while Foldetta (a combined FoldX‑MD and Rosetta stability analysis) is not available for this residue. Given the predominance of pathogenic calls and the SGM‑Consensus result, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-10.605	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous										0.171	Likely Benign	-1.66	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0676	0.2486		4	2	-1.9	18.03
c.592C>T	L198F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198F has no ClinVar entry and is absent from gnomAD. Functional prediction tools split into two consensus groups: benign predictions come from REVEL, Rosetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments are mixed: AlphaMissense‑Optimized and Foldetta report uncertain results, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. No evidence from ClinVar contradicts these findings. Overall, the preponderance of pathogenic predictions and the SGM‑Consensus designation suggest that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-10.602	Likely Pathogenic	0.930	Likely Pathogenic	Ambiguous	1.03	Ambiguous	0.2	0.27	Likely Benign	0.65	Ambiguous	0.00	Likely Benign	0.282	Likely Benign	-3.33	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.39	Benign	0.00	Affected			0.0586	0.3112		2	0	-1.0	34.02
c.2181C>A	N727K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N727K is catalogued in gnomAD (ID 6‑33441646‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, SIFT, and the protein‑folding stability method Foldetta; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the consensus score SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM Consensus indicates likely pathogenic, and Foldetta reports benign stability. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625								6-33441646-C-A	1	6.19e-7	-10.601	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	-0.12	Likely Benign	0.2	-0.44	Likely Benign	-0.28	Likely Benign	0.86	Ambiguous	0.148	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.12	Tolerated	3.59	7	0.2002	0.5590		0	1	-0.4	14.07
c.2181C>G	N727K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence (seven pathogenic vs. five benign, with two uncertain) points to a pathogenic impact. This conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.601	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	-0.12	Likely Benign	0.2	-0.44	Likely Benign	-0.28	Likely Benign	0.86	Ambiguous	0.148	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.12	Tolerated	3.59	7	0.2002	0.5590		0	1	-0.4	14.07
c.1588A>C	K530Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (13/16) predict pathogenicity, whereas only three predict benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-10.593	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	0.31	Likely Benign	0.0	0.87	Ambiguous	0.59	Ambiguous	0.13	Likely Benign	0.524	Likely Pathogenic	-3.18	Deleterious	0.698	Possibly Damaging	0.694	Possibly Damaging	-1.61	Pathogenic	0.01	Affected			0.3001	0.0941		1	1	0.4	-0.04
c.721A>C	K241Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K241Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, FATHMM, and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, nine tools predict pathogenicity versus four predicting benign, with no ClinVar evidence to contradict these findings. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.593	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.33	Likely Benign	0.0	0.46	Likely Benign	0.40	Likely Benign	0.63	Ambiguous	0.767	Likely Pathogenic	-3.33	Deleterious	0.995	Probably Damaging	0.914	Probably Damaging	5.83	Benign	0.04	Affected			0.4225	0.1527		1	1	0.4	-0.04
c.1256A>G	E419G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E419G is listed in ClinVar with an uncertain significance (ClinVar ID 2004834.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms likely pathogenic, and the Foldetta stability analysis is inconclusive. No evidence from FoldX, Rosetta, or premPS is available. Overall, the preponderance of predictions indicates that E419G is most likely pathogenic, which contrasts with the current ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000					Uncertain		1				-10.589	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.41	Ambiguous	0.0	1.94	Ambiguous	1.68	Ambiguous	0.83	Ambiguous	0.469	Likely Benign	-6.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.02	Affected	3.37	29	0.2992	0.5728		0	-2	3.1	-72.06	165.3	110.8	0.0	0.0	-0.1	0.0		X						Potentially Pathogenic	The carboxylate group of Glu419, located on an α helix (res. Met414-Glu436), forms a salt bridge with the side chain of either Arg716 or Lys418 from an opposing helix (res. Pro713-Arg726). The backbone amide group of Glu419 does not form H-bonds, resulting in a slight bend in the α helix. Thus, although glycine is known as an “α helix breaker,” the residue swap does not disrupt the continuity or integrity of the α helix. However, because Gly419 cannot form a salt bridge with the guanidinium group of the Arg716 side chain, the C2-GAP domain tertiary structure could be compromised during folding.
c.754C>G	P252A 2D 3DClick to see structure in 3D Viewer AISynGAP1 P252A is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: a single benign call from FATHMM, and a majority of pathogenic calls from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for P252A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-10.587	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.97	Ambiguous	0.1	1.74	Ambiguous	1.36	Ambiguous	0.69	Ambiguous	0.831	Likely Pathogenic	-7.35	Deleterious	0.941	Possibly Damaging	0.607	Possibly Damaging	5.87	Benign	0.03	Affected			0.3490	0.4161		1	-1	3.4	-26.04
c.1318A>T	N440Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, AlphaMissense‑Default, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicating pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yielding an uncertain stability change. Overall, the majority of predictions lean toward a benign interpretation, and this is consistent with the lack of ClinVar annotation. Therefore, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-10.586	Likely Pathogenic	0.674	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	1.25	Ambiguous	1.03	Ambiguous	0.20	Likely Benign	0.135	Likely Benign	-3.81	Deleterious	0.931	Possibly Damaging	0.230	Benign	3.43	Benign	0.07	Tolerated			0.0535	0.3624		-2	-2	2.2	49.07
c.1890C>G	I630M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I630M is listed in gnomAD (ID 6‑33440942‑C‑G) but has no ClinVar entry. Functional prediction tools show a split: benign calls come from Rosetta, Foldetta, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic calls come from REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. FoldX is uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. High‑accuracy assessments give AlphaMissense‑Optimized benign, Foldetta benign, and an inconclusive SGM Consensus. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.040537	Structured	0.036106	Uncertain	0.966	0.236	0.000								6-33440942-C-G	1	6.20e-7	-10.586	Likely Pathogenic	0.259	Likely Benign	Likely Benign	-0.55	Ambiguous	0.1	0.32	Likely Benign	-0.12	Likely Benign	1.06	Destabilizing	0.508	Likely Pathogenic	-1.90	Neutral	0.833	Possibly Damaging	0.700	Possibly Damaging	-1.38	Pathogenic	0.02	Affected	3.37	34	0.0618	0.1759		1	2	-2.6	18.03
c.1981C>A	Q661K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Only ESM1b predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic, with one uncertain), and Foldetta also predicts benign stability. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-10.581	Likely Pathogenic	0.400	Ambiguous	Likely Benign	-0.01	Likely Benign	0.0	-0.18	Likely Benign	-0.10	Likely Benign	0.04	Likely Benign	0.108	Likely Benign	-1.89	Neutral	0.098	Benign	0.030	Benign	3.59	Benign	0.42	Tolerated			0.1756	0.3592		1	1	-0.4	0.04
c.2845G>T	G949C 2D AIThe SynGAP1 missense variant G949C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988861	Disordered	0.874971	Binding	0.365	0.923	0.750											-10.580	Likely Pathogenic	0.091	Likely Benign	Likely Benign										0.345	Likely Benign	-1.02	Neutral	1.000	Probably Damaging	0.975	Probably Damaging	2.21	Pathogenic	0.01	Affected			0.1480	0.4097		-3	-3	2.9	46.09
c.422T>C	I141T 2D AIThe SynGAP1 missense variant I141T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its contribution is unavailable. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-10.580	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.251	Likely Benign	-2.81	Deleterious	0.272	Benign	0.167	Benign	3.57	Benign	0.00	Affected			0.1165	0.1214		0	-1	-5.2	-12.05
c.3623G>T	R1208L 2D AIThe SynGAP1 missense variant R1208L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that R1208L is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-10.576	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.51	Benign	0.01	Affected			0.1621	0.3816		-3	-2	8.3	-43.03
c.743G>A	R248Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R248Q is catalogued in gnomAD (ID 6‑33435594‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: benign predictions come from FoldX and FATHMM, whereas pathogenic predictions are made by REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are reported by Rosetta and Foldetta. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta remains Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R248Q, and this conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.267126	Uncertain	0.781	0.346	0.250								6-33435594-G-A	2	1.24e-6	-10.573	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.45	Likely Benign	0.2	1.67	Ambiguous	1.06	Ambiguous	1.05	Destabilizing	0.739	Likely Pathogenic	-3.34	Deleterious	0.999	Probably Damaging	0.715	Possibly Damaging	5.74	Benign	0.01	Affected	3.41	14	0.2572	0.2549		1	1	1.0	-28.06
c.1835A>G	Q612R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q612R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are SIFT and FoldX. Tools that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, while AlphaMissense‑Optimized and Foldetta are uncertain. No high‑accuracy tool provides a benign prediction. Overall, the majority of available evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000											-10.571	Likely Pathogenic	0.837	Likely Pathogenic	Ambiguous	-0.35	Likely Benign	0.2	1.56	Ambiguous	0.61	Ambiguous	0.78	Ambiguous	0.683	Likely Pathogenic	-3.85	Deleterious	0.956	Probably Damaging	0.969	Probably Damaging	-1.29	Pathogenic	0.10	Tolerated			0.1480	0.2196		1	1	-1.0	28.06
c.2080G>C	A694P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, while the majority of other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as Likely Pathogenic, with three of four votes pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for A694P. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, and there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-10.569	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.39	Destabilizing	0.2	5.59	Destabilizing	4.49	Destabilizing	0.82	Ambiguous	0.209	Likely Benign	-2.77	Deleterious	0.988	Probably Damaging	0.578	Possibly Damaging	3.44	Benign	0.03	Affected			0.2265	0.3829		1	-1	-3.4	26.04
c.631A>T	S211C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and premPS, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Two tools (Rosetta and AlphaMissense‑Default) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Because the consensus of the most reliable predictors is split (two benign, one pathogenic) and the overall tool distribution is evenly divided, the variant’s impact remains ambiguous. Based on the available predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-10.567	Likely Pathogenic	0.547	Ambiguous	Likely Benign	0.28	Likely Benign	0.1	0.63	Ambiguous	0.46	Likely Benign	0.11	Likely Benign	0.263	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.908	Possibly Damaging	3.89	Benign	0.01	Affected			0.1292	0.5638		0	-1	3.3	16.06
c.1925A>G	K642R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K642R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign. In contrast, PROVEAN, SIFT, and ESM1b predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, Foldetta is benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the balance of evidence favors a benign classification, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-10.562	Likely Pathogenic	0.192	Likely Benign	Likely Benign	-0.13	Likely Benign	0.1	0.39	Likely Benign	0.13	Likely Benign	0.04	Likely Benign	0.319	Likely Benign	-2.79	Deleterious	0.001	Benign	0.001	Benign	2.91	Benign	0.02	Affected			0.4962	0.1262		3	2	-0.6	28.01
c.2152C>A	L718I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718I is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools (Foldetta, premPS, Rosetta) give uncertain results and are not considered evidence. High‑accuracy methods specifically show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Because the majority of reliable predictors (eight out of eleven) indicate pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-10.560	Likely Pathogenic	0.615	Likely Pathogenic	Likely Benign	2.21	Destabilizing	0.2	1.37	Ambiguous	1.79	Ambiguous	0.89	Ambiguous	0.296	Likely Benign	-1.90	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.37	Pathogenic	0.00	Affected			0.0876	0.3206		2	2	0.7	0.00
c.2538A>C	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Overall, the preponderance of evidence from multiple high‑accuracy predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2538A>T	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic or deleterious impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.964G>C	A322P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A322P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, and SIFT, while pathogenic calls are made by SGM‑Consensus, Rosetta, Foldetta, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: FoldX and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Thus, the variant is most likely pathogenic, with no ClinVar evidence to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.425745	Uncertain	0.938	0.334	0.000											-10.558	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	1.26	Ambiguous	1.3	5.43	Destabilizing	3.35	Destabilizing	0.40	Likely Benign	0.343	Likely Benign	-1.72	Neutral	0.784	Possibly Damaging	0.390	Benign	1.90	Pathogenic	0.18	Tolerated			0.2064	0.5400		1	-1	-3.4	26.04
c.1648G>A	A550T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A550T missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SIFT, Rosetta, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. FoldX, Foldetta, and premPS are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta’s stability analysis is uncertain. Overall, the majority of reliable predictors (8/11) indicate a pathogenic impact, whereas only three suggest benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000											-10.555	Likely Pathogenic	0.621	Likely Pathogenic	Likely Benign	1.68	Ambiguous	0.3	-0.05	Likely Benign	0.82	Ambiguous	0.73	Ambiguous	0.627	Likely Pathogenic	-3.19	Deleterious	0.991	Probably Damaging	0.872	Possibly Damaging	-1.25	Pathogenic	0.10	Tolerated			0.0931	0.4465		1	0	-2.5	30.03
c.3764A>T	K1255M 2D AIThe SynGAP1 missense variant K1255M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-10.554	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.393	Likely Benign	-4.82	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.82	Pathogenic	0.00	Affected			0.0776	0.3154		0	-1	5.8	3.02
c.740A>T	Q247L 2D AIThe SynGAP1 missense variant Q247L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence (seven pathogenic versus three benign predictions) points to a pathogenic impact, and this conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.490133	Structured	0.283012	Uncertain	0.822	0.339	0.250											-10.554	Likely Pathogenic	0.352	Ambiguous	Likely Benign	-0.86	Ambiguous	0.5	-1.14	Ambiguous	-1.00	Ambiguous	0.38	Likely Benign	0.687	Likely Pathogenic	-3.89	Deleterious	0.982	Probably Damaging	0.628	Possibly Damaging	5.70	Benign	0.02	Affected			0.0573	0.4129		-2	-2	7.3	-14.97
c.961C>G	R321G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, while the high‑accuracy subset is mixed, with one benign, one pathogenic, and one uncertain result. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125											-10.554	Likely Pathogenic	0.293	Likely Benign	Likely Benign	0.90	Ambiguous	0.1	0.28	Likely Benign	0.59	Ambiguous	0.49	Likely Benign	0.430	Likely Benign	-3.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.92	Pathogenic	0.04	Affected			0.3224	0.2898		-3	-2	4.1	-99.14
c.1488G>C	E496D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E496D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000											-10.552	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.2	1.78	Ambiguous	1.11	Ambiguous	1.18	Destabilizing	0.583	Likely Pathogenic	-2.78	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	-1.45	Pathogenic	0.04	Affected	3.37	35	0.1576	0.1912		2	3	0.0	-14.03
c.1488G>T	E496D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E496D is reported in gnomAD (ID 6‑33438520‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions are provided only by FoldX, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—classify the change as pathogenic. Uncertain results come from Rosetta, Foldetta, and AlphaMissense‑Optimized and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000								6-33438520-G-T	2	1.24e-6	-10.552	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.2	1.78	Ambiguous	1.11	Ambiguous	1.18	Destabilizing	0.583	Likely Pathogenic	-2.78	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	-1.45	Pathogenic	0.04	Affected	3.37	35	0.1576	0.1912		2	3	0.0	-14.03
c.752A>C	K251T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K251T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include premPS, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) supports a pathogenic prediction, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the balance of evidence favors a pathogenic effect for K251T, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-10.552	Likely Pathogenic	0.841	Likely Pathogenic	Ambiguous	1.21	Ambiguous	0.4	0.50	Ambiguous	0.86	Ambiguous	0.46	Likely Benign	0.742	Likely Pathogenic	-2.72	Deleterious	0.970	Probably Damaging	0.749	Possibly Damaging	5.76	Benign	0.28	Tolerated			0.2353	0.2852		0	-1	3.2	-27.07
c.1456G>C	E486Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and AlphaMissense‑Optimized as uncertain. No prediction or stability result is missing or inconclusive beyond the stated uncertainty. Overall, the evidence is balanced, with an equal number of benign and pathogenic calls, and the high‑accuracy tools provide opposing conclusions. Thus, the variant is most likely benign based on the preponderance of benign predictions, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.549	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.12	Likely Benign	0.1	0.00	Likely Benign	0.06	Likely Benign	0.24	Likely Benign	0.334	Likely Benign	-2.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.38	Benign	0.09	Tolerated			0.0888	0.5880		2	2	0.0	-0.98
c.1943T>G	F648C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a deleterious effect: all evaluated algorithms except FATHMM predict pathogenicity, while FATHMM alone predicts benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a pathogenic effect. In summary, the overwhelming consensus from both general and high‑accuracy predictors is that F648C is pathogenic. This conclusion is consistent with the absence of any ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-10.547	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.28	Destabilizing	0.1	3.35	Destabilizing	3.32	Destabilizing	1.22	Destabilizing	0.621	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.40	Benign	0.03	Affected			0.2283	0.0783		-4	-2	-0.3	-44.04
c.1046C>A	P349Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 P349Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy assessments further clarify the variant’s likely effect: AlphaMissense‑Optimized predicts a benign outcome; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-10.545	Likely Pathogenic	0.508	Ambiguous	Likely Benign	0.98	Ambiguous	0.1	1.87	Ambiguous	1.43	Ambiguous	0.91	Ambiguous	0.345	Likely Benign	-6.40	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.54	Pathogenic	0.06	Tolerated			0.1480	0.4766		0	-1	-1.9	31.01
c.559C>G	L187V 2D AIThe SynGAP1 missense variant L187V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors lean toward a benign classification, but the single high‑accuracy tool indicates pathogenicity. Thus, the variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-10.543	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.136	Likely Benign	-2.24	Neutral	0.437	Benign	0.079	Benign	3.81	Benign	0.02	Affected			0.1525	0.3509		2	1	0.4	-14.03
c.862G>A	D288N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D288N is listed in ClinVar with an uncertain significance (ClinVar ID 2572204.0) and is present in gnomAD (6‑33437767‑G‑A). Computational predictors are divided: benign calls come from REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic. Because the majority of high‑accuracy tools predict benign and the overall split of predictions is even, the variant is most likely benign, which does not contradict the ClinVar status of uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000					Uncertain		1	6-33437767-G-A	2	1.24e-6	-10.535	Likely Pathogenic	0.521	Ambiguous	Likely Benign	-0.39	Likely Benign	0.1	0.01	Likely Benign	-0.19	Likely Benign	-0.03	Likely Benign	0.321	Likely Benign	-3.73	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.78	Pathogenic	0.05	Affected	3.38	23	0.1398	0.5770		1	2	0.0	-0.98
c.773G>A	R258H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R258H is listed as Benign in ClinVar (ID 949697.0) and is present in gnomAD (6‑33437678‑G‑A). Prediction tools that agree on a benign effect include FATHMM and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain calls come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. The high‑accuracy consensus (SGM) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic verdict. AlphaMissense‑Optimized remains benign, while Foldetta is inconclusive. Overall, the majority of evidence points to a pathogenic impact, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.295083	Structured	0.293667	Uncertain	0.894	0.260	0.250					Benign/Likely benign		3	6-33437678-G-A	10	6.20e-6	-10.533	Likely Pathogenic	0.525	Ambiguous	Likely Benign	1.60	Ambiguous	0.6	1.00	Ambiguous	1.30	Ambiguous	1.47	Destabilizing	0.830	Likely Pathogenic	-4.06	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	5.77	Benign	0.01	Affected	3.39	15	0.2925	0.1980		2	0	1.3	-19.05	212.5	81.8	0.1	0.0	-0.5	0.2		X						Potentially Pathogenic	The guanidinium group of Arg258, located at the end of an α-β loop connecting the PH domain to the C2 domain (res. Lys251-Arg258), forms hydrogen bonds with the carboxamide groups of Asn727 and Asn729 side chains, as well as with the backbone carbonyl groups of Ala724, Leu725, and Asn727 in the WT simulations. Although the imidazole group of His258 can act as a hydrogen bond donor/acceptor, the swapped residue is unable to maintain an equally well-coordinated hydrogen bond network for linking the C2 and GAP domains in the variant simulations.
c.648G>C	Q216H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas those that predict a pathogenic impact are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.532	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	0.638	Likely Pathogenic	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			0.1909	0.4660		3	0	0.3	9.01
c.648G>T	Q216H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.532	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	0.638	Likely Pathogenic	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			0.1909	0.4660		3	0	0.3	9.01
c.1001A>T	K334M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, and premPS. In contrast, the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. Foldetta and Rosetta provide uncertain results. Focusing on high‑accuracy methods, AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus confirms a Likely Pathogenic status, and Foldetta remains inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K334M, and this assessment does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-10.530	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.0	0.56	Ambiguous	0.50	Ambiguous	0.14	Likely Benign	0.323	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.77	Pathogenic	0.01	Affected			0.1027	0.3690		0	-1	5.8	3.02
c.1221G>C	Q407H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407H (C2 domain) has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is uncertain. No evidence from FoldX, Rosetta, or Foldetta supports a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	0.206	Likely Benign	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0.1205	0.3154		0	3	0.3	9.01
c.1221G>T	Q407H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q407H is listed in ClinVar with an uncertain significance (ClinVar ID 2772184.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked as uncertain include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Q407H. This conclusion does not conflict with the ClinVar designation of uncertain significance, which remains unresolved pending further evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000					Uncertain		1				-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	0.206	Likely Benign	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0.1205	0.3154		0	3	0.3	9.01
c.2144C>A	P715H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of predictors (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) indicate a pathogenic impact. Tools with inconclusive results (Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the consensus of the majority of evidence points to a pathogenic effect for P715H. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-10.523	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	2.80	Destabilizing	0.0	0.28	Likely Benign	1.54	Ambiguous	0.56	Ambiguous	0.271	Likely Benign	-7.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.37	Benign	0.00	Affected			0.1413	0.3684		0	-2	-1.6	40.02
c.2099T>A	L700Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700Q is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized indicates a benign change, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both predict pathogenicity. No predictions are missing or inconclusive. Overall, the preponderance of evidence from the majority of tools points to a pathogenic effect, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-10.522	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	2.41	Destabilizing	0.1	4.02	Destabilizing	3.22	Destabilizing	1.35	Destabilizing	0.321	Likely Benign	-3.79	Deleterious	0.994	Probably Damaging	0.896	Possibly Damaging	3.34	Benign	0.01	Affected			0.1074	0.0488		-2	-2	-7.3	14.97
c.2116G>A	E706K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E706K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM all classify the change as benign. In contrast, ESM1b and AlphaMissense‑Default predict a pathogenic impact. Tools that return uncertain results—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—do not provide decisive evidence. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign calls). High‑accuracy assessments are likewise ambiguous: AlphaMissense‑Optimized is uncertain, Foldetta is uncertain, and the SGM Consensus remains inconclusive. Overall, the preponderance of evidence points to a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000					Uncertain		1				-10.519	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	1.17	Ambiguous	0.1	0.51	Ambiguous	0.84	Ambiguous	0.08	Likely Benign	0.080	Likely Benign	-1.51	Neutral	0.345	Benign	0.028	Benign	4.15	Benign	0.52	Tolerated	3.47	10	0.2065	0.4511		0	1	-0.4	-0.94	187.1	49.2	0.0	0.0	0.4	0.1						X		Uncertain	The carboxylate side chain of Glu706, located at the end and outer surface of an α-helix (res. Thr704-Gly712), forms a salt bridge with Lys710 and a hydrogen bond with its own backbone amino group at the helix end in the WT simulations. Although Lys706 is unable to make these transient interactions in the variant simulations, there is no apparent negative effect on the protein structure due to the residue swap. However, because the model ends abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.611C>A	S204Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S204Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) is inconclusive because it receives an equal split between pathogenic and benign calls. AlphaMissense‑Optimized, a high‑accuracy model, predicts benign, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts pathogenic. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.268042	Structured	0.420667	Uncertain	0.816	0.405	0.125											-10.518	Likely Pathogenic	0.782	Likely Pathogenic	Likely Benign	8.99	Destabilizing	3.8	5.20	Destabilizing	7.10	Destabilizing	-0.03	Likely Benign	0.170	Likely Benign	-0.96	Neutral	0.978	Probably Damaging	0.694	Possibly Damaging	4.14	Benign	0.03	Affected			0.0452	0.5625		-3	-2	-0.5	76.10
c.1556A>T	E519V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight the discord: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates benign stability. Overall, the preponderance of evidence points to a pathogenic effect for E519V. This conclusion does not conflict with ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-10.513	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.59	Ambiguous	0.0	-0.40	Likely Benign	0.10	Likely Benign	0.16	Likely Benign	0.400	Likely Benign	-6.33	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	3.20	Benign	0.00	Affected			0.0825	0.4369		-2	-2	7.7	-29.98
c.1565A>C	E522A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E522A is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the preponderance of evidence (10 pathogenic vs. 4 benign predictions) indicates that E522A is most likely pathogenic, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.509	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	0.01	Likely Benign	0.10	Likely Benign	0.40	Likely Benign	0.739	Likely Pathogenic	-5.67	Deleterious	0.998	Probably Damaging	0.999	Probably Damaging	-1.34	Pathogenic	0.02	Affected			0.3137	0.4128		0	-1	5.3	-58.04
c.770G>A	S257N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S257N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: benign calls come from FoldX, Rosetta, Foldetta, PROVEAN, SIFT, and FATHMM, while pathogenic calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments give an inconclusive SGM Consensus (a tie between AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), an uncertain AlphaMissense‑Optimized result, and a benign Foldetta prediction. No evidence of pathogenicity is supported by the protein‑stability analysis, which indicates a benign effect. Overall, the predictions are mixed, but the majority of high‑accuracy tools lean toward a benign interpretation. This assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.384043	Structured	0.258293	Uncertain	0.847	0.272	0.250											-10.508	Likely Pathogenic	0.820	Likely Pathogenic	Ambiguous	0.25	Likely Benign	0.1	-0.18	Likely Benign	0.04	Likely Benign	0.85	Ambiguous	0.533	Likely Pathogenic	-2.30	Neutral	0.993	Probably Damaging	0.968	Probably Damaging	5.82	Benign	0.16	Tolerated			0.0985	0.3596		1	1	-2.7	27.03
c.3709T>A	Y1237N 2D AIThe SynGAP1 missense variant Y1237N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-10.505	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.413	Likely Benign	-7.18	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.44	Pathogenic	0.00	Affected			0.2428	0.0173		-2	-2	-2.2	-49.07
c.466T>A	F156I 2D AIThe SynGAP1 missense variant F156I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-10.505	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.38	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.99	Benign	0.00	Affected			0.1960	0.1938		1	0	1.7	-34.02
c.2038G>C	E680Q 2D AIThe SynGAP1 missense variant E680Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a benign impact for E680Q. This conclusion is not contradicted by ClinVar, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-10.502	Likely Pathogenic	0.742	Likely Pathogenic	Likely Benign	-0.01	Likely Benign	0.7	-0.01	Likely Benign	-0.01	Likely Benign	-0.10	Likely Benign	0.239	Likely Benign	-2.58	Deleterious	0.981	Probably Damaging	0.483	Possibly Damaging	3.47	Benign	0.15	Tolerated			0.1751	0.7241		2	2	0.0	-0.98
c.2143C>A	P715T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. Two tools, Foldetta and premPS, returned uncertain results. High‑accuracy analyses further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenicity; Foldetta remains inconclusive. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-10.501	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign	2.55	Destabilizing	0.1	0.29	Likely Benign	1.42	Ambiguous	0.72	Ambiguous	0.368	Likely Benign	-7.23	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.37	Benign	0.01	Affected			0.1357	0.4072		0	-1	0.9	3.99
c.2458T>G	Y820D 2D AIThe SynGAP1 missense variant Y820D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that Y820D is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-10.497	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-2.77	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.73	Benign	0.08	Tolerated			0.4113	0.0704		-4	-3	-2.2	-48.09
c.910G>T	D304Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, and premPS, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. With the majority of evidence pointing toward pathogenicity, the variant is most likely pathogenic; this assessment does not conflict with ClinVar, which contains no entry for D304Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-10.495	Likely Pathogenic	0.845	Likely Pathogenic	Ambiguous	0.60	Ambiguous	0.2	0.14	Likely Benign	0.37	Likely Benign	0.37	Likely Benign	0.468	Likely Benign	-6.29	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.76	Pathogenic	0.00	Affected			0.0623	0.6566		-4	-3	2.2	48.09
c.1390T>C	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.435	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>A	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>G	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1726T>A	C576S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions from REVEL and FATHMM, while the majority of other in silico methods (premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic. Foldetta remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented tools and the high‑accuracy predictions indicates that C576S is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-10.474	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.77	Ambiguous	0.1	1.57	Ambiguous	1.17	Ambiguous	1.61	Destabilizing	0.414	Likely Benign	-8.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.02	Affected			0.4968	0.1464		0	-1	-3.3	-16.06
c.1727G>C	C576S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576S is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect are limited to FATHMM, whereas the remaining 11 tools (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic or likely pathogenic outcome. High‑accuracy methods reinforce this trend: AlphaMissense‑Optimized reports pathogenic; the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also returns likely pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta, is inconclusive. Folding‑stability tools FoldX and Rosetta individually yield uncertain results and are treated as unavailable. Taken together, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-10.474	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.77	Ambiguous	0.1	1.57	Ambiguous	1.17	Ambiguous	1.61	Destabilizing	0.523	Likely Pathogenic	-8.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.02	Affected			0.4968	0.1464		0	-1	-3.3	-16.06
c.1826G>A	G609E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G609E has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools (Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.203786	Uncertain	0.851	0.252	0.000											-10.470	Likely Pathogenic	0.421	Ambiguous	Likely Benign	2.95	Destabilizing	0.4	-1.65	Ambiguous	0.65	Ambiguous	0.61	Ambiguous	0.531	Likely Pathogenic	-2.28	Neutral	0.916	Possibly Damaging	0.588	Possibly Damaging	-1.41	Pathogenic	0.17	Tolerated			0.1709	0.4491		0	-2	-3.1	72.06
c.827C>A	P276H 2D 3DClick to see structure in 3D Viewer AISynGAP1 P276H is reported in gnomAD (ID 6‑33437732‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic, while only AlphaMissense‑Optimized predicts a benign outcome. Uncertain results are provided by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.037156	Structured	0.338937	Uncertain	0.724	0.230	0.250								6-33437732-C-A	1	6.20e-7	-10.469	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	1.98	Ambiguous	0.1	1.09	Ambiguous	1.54	Ambiguous	0.85	Ambiguous	0.534	Likely Pathogenic	-4.80	Deleterious	1.000	Probably Damaging	0.961	Probably Damaging	1.84	Pathogenic	0.00	Affected	3.38	19	0.1739	0.3439		-2	0	-1.6	40.02
c.2135G>T	G712V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G712V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000											-10.466	Likely Pathogenic	0.877	Likely Pathogenic	Ambiguous	3.79	Destabilizing	0.0	6.18	Destabilizing	4.99	Destabilizing	0.79	Ambiguous	0.410	Likely Benign	-7.55	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.32	Benign	0.00	Affected			0.1395	0.3712		-1	-3	4.6	42.08
c.1283A>T	Y428F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact. Uncertain or inconclusive results are reported for FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as unavailable. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a pathogenic SGM Consensus and a benign AlphaMissense‑Optimized—suggests that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-10.464	Likely Pathogenic	0.530	Ambiguous	Likely Benign	0.82	Ambiguous	0.1	0.52	Ambiguous	0.67	Ambiguous	0.89	Ambiguous	0.366	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.41	Benign	0.04	Affected			0.2719	0.3146		7	3	4.1	-16.00
c.899C>A	S300Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S300Y has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Foldetta, premPS, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Two tools (AlphaMissense‑Default and Rosetta) are uncertain and do not influence the consensus. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not contradict any ClinVar status (none is available). Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.356642	Structured	0.256848	Uncertain	0.742	0.280	0.375											-10.464	Likely Pathogenic	0.422	Ambiguous	Likely Benign	-0.08	Likely Benign	0.4	0.55	Ambiguous	0.24	Likely Benign	0.28	Likely Benign	0.116	Likely Benign	-2.52	Deleterious	0.975	Probably Damaging	0.686	Possibly Damaging	1.52	Pathogenic	0.01	Affected			0.0678	0.5395		-3	-2	-0.5	76.10
c.1649C>T	A550V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A550V variant has no ClinVar entry and is catalogued in gnomAD (ID 6‑33438892‑C‑T). Prediction tools that agree on a benign effect include Foldetta, premPS, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results come from FoldX and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as pathogenic, and Foldetta as benign. Overall, the majority of tools (seven versus four) favor a pathogenic interpretation, and this does not contradict any ClinVar classification because none is available. Thus, based on the current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000								6-33438892-C-T	1	6.20e-7	-10.461	Likely Pathogenic	0.441	Ambiguous	Likely Benign	0.77	Ambiguous	0.2	-0.05	Likely Benign	0.36	Likely Benign	0.48	Likely Benign	0.540	Likely Pathogenic	-2.93	Deleterious	0.984	Probably Damaging	0.494	Possibly Damaging	-1.05	Pathogenic	0.39	Tolerated	3.37	33	0.0874	0.4370		0	0	2.4	28.05
c.1975T>C	S659P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are SGM‑Consensus, Rosetta, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, premPS, and Foldetta—are treated as unavailable. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized reports a benign change, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta’s stability assessment is uncertain. Overall, the balance of evidence leans toward a pathogenic effect, but the presence of a strong benign prediction from AlphaMissense‑Optimized and the lack of ClinVar annotation means the variant’s clinical significance remains uncertain and does not contradict existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-10.461	Likely Pathogenic	0.609	Likely Pathogenic	Likely Benign	-0.73	Ambiguous	0.3	2.98	Destabilizing	1.13	Ambiguous	0.73	Ambiguous	0.224	Likely Benign	-3.26	Deleterious	0.932	Possibly Damaging	0.245	Benign	3.39	Benign	0.18	Tolerated			0.2207	0.5553		1	-1	-0.8	10.04
c.3176G>A	G1059E 2D AIThe SynGAP1 missense variant G1059E is reported in gnomAD (variant ID 6‑33443728‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only two tools—SIFT and ESM1b—predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.983019	Disordered	0.898939	Binding	0.399	0.926	0.875								6-33443728-G-A	1	6.22e-7	-10.459	Likely Pathogenic	0.297	Likely Benign	Likely Benign										0.390	Likely Benign	-0.71	Neutral	0.126	Benign	0.066	Benign	2.53	Benign	0.00	Affected	4.32	2	0.1464	0.4069		-2	0	-3.1	72.06
c.1962G>C	E654D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E654D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the predictions are mixed, with a slight majority leaning toward benign, but the high‑accuracy tools conflict. The variant is most likely benign based on the aggregate predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.454	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.0	0.52	Ambiguous	0.48	Likely Benign	0.29	Likely Benign	0.166	Likely Benign	-2.87	Deleterious	0.906	Possibly Damaging	0.429	Benign	3.38	Benign	0.11	Tolerated			0.1678	0.2583		3	2	0.0	-14.03
c.1962G>T	E654D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E654D has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain (treated as unavailable), SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. No other folding‑stability results are available. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.454	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.0	0.52	Ambiguous	0.48	Likely Benign	0.29	Likely Benign	0.166	Likely Benign	-2.87	Deleterious	0.906	Possibly Damaging	0.429	Benign	3.38	Benign	0.11	Tolerated			0.1678	0.2583		3	2	0.0	-14.03
c.2129A>C	K710T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K710T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain (no definitive stability change). Other stability predictions (FoldX, Rosetta) are also uncertain and thus unavailable for interpretation. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-10.454	Likely Pathogenic	0.759	Likely Pathogenic	Likely Benign	1.02	Ambiguous	0.0	1.57	Ambiguous	1.30	Ambiguous	0.21	Likely Benign	0.305	Likely Benign	-5.45	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.41	Benign	0.06	Tolerated			0.1487	0.3000		0	-1	3.2	-27.07
c.932A>C	H311P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H311P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign outcome; the remaining predictions are uncertain (FoldX, Foldetta, premPS, AlphaMissense‑Optimized). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the majority of evidence points to a deleterious impact on protein function. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for H311P. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125											-10.454	Likely Pathogenic	0.869	Likely Pathogenic	Ambiguous	1.57	Ambiguous	0.6	2.39	Destabilizing	1.98	Ambiguous	0.74	Ambiguous	0.724	Likely Pathogenic	-7.76	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.87	Pathogenic	0.01	Affected			0.2173	0.4172		0	-2	1.6	-40.02
c.406C>T	R136W 2D AIThe SynGAP1 missense variant R136W is listed in ClinVar (ID 1479441.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a deleterious effect, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.433034	Structured	0.657394	Binding	0.351	0.894	0.250					Uncertain		2				-10.453	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.237	Likely Benign	-4.71	Deleterious	0.965	Probably Damaging	0.416	Benign	3.45	Benign	0.00	Affected	3.61	5	0.1189	0.3827		2	-3	3.6	30.03
c.1999A>C	I667L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I667L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, indicating no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-10.452	Likely Pathogenic	0.459	Ambiguous	Likely Benign	0.93	Ambiguous	0.2	0.72	Ambiguous	0.83	Ambiguous	0.75	Ambiguous	0.300	Likely Benign	-1.97	Neutral	0.457	Possibly Damaging	0.392	Benign	3.36	Benign	0.13	Tolerated			0.0980	0.3145		2	2	-0.7	0.00
c.731A>G	E244G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of computational evidence points to the variant being most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-10.452	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.28	Ambiguous	0.0	0.74	Ambiguous	1.01	Ambiguous	1.01	Destabilizing	0.900	Likely Pathogenic	-5.67	Deleterious	0.990	Probably Damaging	0.815	Possibly Damaging	5.73	Benign	0.01	Affected			0.2266	0.5252		0	-2	3.1	-72.06
c.1802C>T	A601V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A601V is listed in ClinVar (ID 968190.0) with an uncertain clinical significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from Rosetta and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. Four tools (FoldX, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000					Uncertain		1				-10.447	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous	1.64	Ambiguous	0.1	0.35	Likely Benign	1.00	Ambiguous	0.81	Ambiguous	0.535	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.74	Benign	0.03	Affected	3.37	35	0.1338	0.5263		0	0	2.4	28.05	228.5	-45.5	0.0	0.0	0.4	0.5						X		Potentially Benign	The methyl side chain of Ala601, located on an α helix (res. Glu582-Met603), packs hydrophobically against other hydrophobic residues in the inter-helix space (e.g., Phe597, Leu598, Leu506, Phe608).In the variant simulations, Val601, which has similar size and physicochemical properties to alanine, resides in the inter-helix hydrophobic space in a similar manner to Ala601 in the WT, causing no apparent negative effect on the protein structure. However, the effect of the residue swap on the SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.3650A>C	E1217A 2D AIThe SynGAP1 missense variant E1217A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show a split: AlphaMissense‑Optimized reports benign, while the SGM‑Consensus (majority vote) reports likely pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for E1217A, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-10.446	Likely Pathogenic	0.605	Likely Pathogenic	Likely Benign										0.261	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.2585	0.4401		0	-1	5.3	-58.04
c.1274C>T	T425I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425I is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the balance of evidence slightly favors a pathogenic interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-10.443	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	-0.04	Likely Benign	0.2	0.07	Likely Benign	0.02	Likely Benign	0.30	Likely Benign	0.268	Likely Benign	-5.30	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.44	Benign	0.06	Tolerated			0.0827	0.4023		0	-1	5.2	12.05
c.1807A>G	M603V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M603V is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS and SIFT, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic, and AlphaMissense‑Optimized is uncertain; Foldetta also remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for M603V. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-10.442	Likely Pathogenic	0.800	Likely Pathogenic	Ambiguous	1.34	Ambiguous	0.2	0.62	Ambiguous	0.98	Ambiguous	-0.15	Likely Benign	0.668	Likely Pathogenic	-3.48	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-0.92	Pathogenic	0.09	Tolerated			0.2698	0.2601		2	1	2.3	-32.06
c.1196C>A	A399D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A399D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that agree on a pathogenic effect are REVEL, FoldX, SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy methods give no definitive verdict: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie and thus unavailable, and Foldetta is uncertain. Overall, the majority of available predictions (five pathogenic vs. four benign) lean toward pathogenicity. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.394753	Structured	0.407674	Uncertain	0.939	0.490	0.125											-10.441	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	2.45	Destabilizing	0.2	1.17	Ambiguous	1.81	Ambiguous	0.91	Ambiguous	0.525	Likely Pathogenic	-1.84	Neutral	0.421	Benign	0.054	Benign	5.38	Benign	0.05	Affected			0.1533	0.1760		0	-2	-5.3	44.01
c.1031G>C	G344A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G344A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default, while only SIFT predicts a benign outcome. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Overall, the consensus of the majority of predictors indicates a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.264545	Structured	0.368110	Uncertain	0.913	0.485	0.250											-10.439	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous	5.11	Destabilizing	0.4	4.23	Destabilizing	4.67	Destabilizing	0.58	Ambiguous	0.873	Likely Pathogenic	-5.38	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-0.32	Pathogenic	0.10	Tolerated			0.3964	0.5685		1	0	2.2	14.03
c.1358A>T	H453L 2D 3DClick to see structure in 3D Viewer AISynGAP1 H453L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, premPS, SIFT, FATHMM, and the protein‑folding stability method Foldetta; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments indicate that AlphaMissense‑Optimized is uncertain, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the predictions are split, with a slight edge toward pathogenicity from the consensus and high‑accuracy tools, but the presence of several benign calls and the uncertainty of AlphaMissense‑Optimized temper this conclusion. Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-10.438	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous	-0.59	Ambiguous	0.1	0.04	Likely Benign	-0.28	Likely Benign	0.31	Likely Benign	0.413	Likely Benign	-10.87	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.45	Benign	0.11	Tolerated			0.0841	0.4964		-2	-3	7.0	-23.98
c.2110A>T	S704C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Other stability‑based tools such as FoldX, Rosetta, and premPS also return uncertain results. Overall, the majority of individual predictors lean toward pathogenicity, and the high‑accuracy consensus also supports a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-10.438	Likely Pathogenic	0.423	Ambiguous	Likely Benign	1.56	Ambiguous	0.1	0.98	Ambiguous	1.27	Ambiguous	0.52	Ambiguous	0.251	Likely Benign	-3.52	Deleterious	0.997	Probably Damaging	0.789	Possibly Damaging	3.40	Benign	0.01	Affected			0.0789	0.4612		0	-1	3.3	16.06
c.3722T>A	L1241Q 2D AIThe SynGAP1 missense variant L1241Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-10.429	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.386	Likely Benign	-4.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.1217	0.0488		-2	-2	-7.3	14.97
c.1592G>T	C531F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Rosetta and polyPhen‑2 HumVar, while the majority of tools (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Tools with inconclusive or uncertain results are AlphaMissense‑Optimized, Foldetta, and premPS. High‑accuracy assessments show SGM‑Consensus as “Likely Pathogenic”; AlphaMissense‑Optimized is uncertain; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also uncertain. Taken together, the preponderance of evidence from multiple pathogenic‑predicting algorithms and the SGM‑Consensus score indicates that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-10.428	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	2.47	Destabilizing	1.6	0.26	Likely Benign	1.37	Ambiguous	0.59	Ambiguous	0.519	Likely Pathogenic	-8.89	Deleterious	0.866	Possibly Damaging	0.244	Benign	-1.23	Pathogenic	0.01	Affected			0.1103	0.3784		-4	-2	0.3	44.04
c.1355T>C	V452A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V452A is not reported in ClinVar and has no entry in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta remains inconclusive. Overall, the consensus of the available tools points to a pathogenic effect for V452A, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000											-10.423	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.21	Destabilizing	0.0	1.51	Ambiguous	1.86	Ambiguous	2.18	Destabilizing	0.505	Likely Pathogenic	-3.95	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.21	Benign	0.00	Affected			0.2642	0.2521		0	0	-2.4	-28.05
c.3712C>G	Q1238E 2D AIThe SynGAP1 missense variant Q1238E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically show AlphaMissense‑Optimized predicting benign, while SGM Consensus and Foldetta are unavailable. Overall, the majority of standard predictors (5 pathogenic vs 4 benign) lean toward a pathogenic interpretation, and this assessment does not contradict ClinVar status because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-10.421	Likely Pathogenic	0.312	Likely Benign	Likely Benign										0.201	Likely Benign	-1.90	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.37	Pathogenic	0.02	Affected			0.1078	0.1921		2	2	0.0	0.98
c.977A>T	H326L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H326L missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include SIFT, premPS, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) predicts benign. No evidence is available from FoldX or AlphaMissense‑Optimized to support either outcome. Overall, the majority of predictions (nine pathogenic vs. four benign) indicate that H326L is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-10.421	Likely Pathogenic	0.888	Likely Pathogenic	Ambiguous	-0.85	Ambiguous	0.2	0.36	Likely Benign	-0.25	Likely Benign	0.44	Likely Benign	0.627	Likely Pathogenic	-9.64	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.08	Tolerated			0.0992	0.5799		-2	-3	7.0	-23.98
c.1877T>C	I626T 2D AISynGAP1 missense variant I626T is listed in ClinVar with an uncertain significance (ClinVar ID 3359331.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the consensus of the majority of tools points to a pathogenic effect, contradicting the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000					Uncertain		1				-10.420	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.94	Destabilizing	0.1	2.70	Destabilizing	2.82	Destabilizing	2.23	Destabilizing	0.640	Likely Pathogenic	-4.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.04	Benign	0.00	Affected			0.1000	0.0840		0	-1	-5.2	-12.05
c.1751T>C	I584T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I584T is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors indicates a pathogenic effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as likely pathogenic. Only AlphaMissense‑Optimized predicts a benign outcome, while Rosetta and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. With the overwhelming majority of tools supporting pathogenicity and no ClinVar entry to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000											-10.413	Likely Pathogenic	0.765	Likely Pathogenic	Likely Benign	2.05	Destabilizing	0.1	1.70	Ambiguous	1.88	Ambiguous	1.66	Destabilizing	0.748	Likely Pathogenic	-4.63	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.11	Pathogenic	0.02	Affected			0.0911	0.0608		0	-1	-5.2	-12.05
c.538T>G	S180A 2D AIThe SynGAP1 missense variant S180A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the S180A variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-10.413	Likely Pathogenic	0.559	Ambiguous	Likely Benign										0.095	Likely Benign	-1.94	Neutral	0.390	Benign	0.079	Benign	3.90	Benign	0.04	Affected			0.5003	0.3788	Weaken	1	1	2.6	-16.00
c.592C>A	L198I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198I is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain or inconclusive results come from AlphaMissense‑Default, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-10.411	Likely Pathogenic	0.563	Ambiguous	Likely Benign	0.59	Ambiguous	0.1	0.70	Ambiguous	0.65	Ambiguous	0.10	Likely Benign	0.234	Likely Benign	-1.72	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	3.43	Benign	0.00	Affected			0.0921	0.3307		2	2	0.7	0.00
c.1324A>C	K442Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K442Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-10.410	Likely Pathogenic	0.562	Ambiguous	Likely Benign	0.05	Likely Benign	0.1	0.03	Likely Benign	0.04	Likely Benign	0.25	Likely Benign	0.268	Likely Benign	-3.10	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.39	Benign	0.18	Tolerated			0.3353	0.1014		1	1	0.4	-0.04
c.260C>A	S87Y 2D AIThe SynGAP1 missense variant S87Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.550904	Binding	0.302	0.878	0.500											-10.410	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.052	Likely Benign	-2.20	Neutral	0.880	Possibly Damaging	0.608	Possibly Damaging	3.75	Benign	0.00	Affected			0.0522	0.4798		-3	-2	-0.5	76.10
c.452A>G	D151G 2D AIThe SynGAP1 D151G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and FATHMM, whereas the remaining eight tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence indicates that D151G is most likely pathogenic, and this assessment does not conflict with any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-10.409	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.349	Likely Benign	-3.91	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.87	Benign	0.01	Affected			0.4452	0.7037		1	-1	3.1	-58.04
c.3371G>A	G1124E 2D AIThe SynGAP1 missense variant G1124E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome (2 benign vs. 1 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.837511	Disordered	0.833401	Binding	0.341	0.931	0.875											-10.403	Likely Pathogenic	0.345	Ambiguous	Likely Benign										0.301	Likely Benign	-0.84	Neutral	0.126	Benign	0.066	Benign	4.78	Benign	0.02	Affected			0.1405	0.4063		0	-2	-3.1	72.06
c.3686A>C	Q1229P 2D AIThe SynGAP1 missense variant Q1229P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is “Likely Pathogenic.” No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375					Uncertain		1				-10.397	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.422	Likely Benign	-3.69	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.75	Pathogenic	0.12	Tolerated	3.77	5	0.2197	0.4107		0	-1	1.9	-31.01
c.3592T>C	Y1198H 2D AIThe SynGAP1 missense variant Y1198H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-10.394	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.246	Likely Benign	-2.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.19	Tolerated			0.1975	0.0373		0	2	-1.9	-26.03
c.1156G>T	G386W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G386W is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Computational predictors that classify the change as benign include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. High‑accuracy assessments give a benign verdict from AlphaMissense‑Optimized, a benign consensus from the SGM method (majority of the four contributing tools are benign), and a pathogenic result from Foldetta. Uncertain calls from AlphaMissense‑Default and Rosetta are treated as unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750											-10.389	Likely Pathogenic	0.519	Ambiguous	Likely Benign	6.07	Destabilizing	5.5	1.28	Ambiguous	3.68	Destabilizing	-0.23	Likely Benign	0.471	Likely Benign	-0.85	Neutral	0.996	Probably Damaging	0.920	Probably Damaging	3.90	Benign	0.00	Affected			0.1058	0.4676		-7	-2	-0.5	129.16
c.535G>C	E179Q 2D AIThe SynGAP1 missense variant E179Q has no ClinVar record (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Computational predictions are split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy consensus tools are inconclusive: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic based on current predictions, and there is no ClinVar status to contradict this ambiguous assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-10.388	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-1.82	Neutral	0.818	Possibly Damaging	0.419	Benign	3.99	Benign	0.02	Affected			0.1674	0.7383		2	2	0.0	-0.98
c.788T>G	V263G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V263G missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized; those that agree on a pathogenic effect are REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence points to a pathogenic impact for V263G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.268042	Structured	0.356141	Uncertain	0.918	0.257	0.000											-10.388	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	2.27	Destabilizing	0.2	1.63	Ambiguous	1.95	Ambiguous	1.88	Destabilizing	0.820	Likely Pathogenic	-4.59	Deleterious	0.991	Probably Damaging	0.999	Probably Damaging	6.07	Benign	0.01	Affected			0.1790	0.1868		-1	-3	-4.6	-42.08
c.1516C>A	L506I 2D AIThe SynGAP1 missense variant L506I is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Uncertain results are reported by FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments give a pathogenic verdict from Foldetta (a combined FoldX‑MD/Rosetta stability analysis) and from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). AlphaMissense‑Optimized, however, predicts benign. Overall, the majority of reliable tools and the high‑accuracy methods favor a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-10.386	Likely Pathogenic	0.501	Ambiguous	Likely Benign	1.73	Ambiguous	1.0	2.85	Destabilizing	2.29	Destabilizing	0.98	Ambiguous	0.365	Likely Benign	-1.99	Neutral	0.998	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.0745	0.2033		2	2	0.7	0.00
c.1982A>G	Q661R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are polyPhen2_HumDiv and ESM1b. FoldX, Rosetta, Foldetta, and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the majority of available evidence points to a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-10.386	Likely Pathogenic	0.479	Ambiguous	Likely Benign	-1.12	Ambiguous	0.0	-0.59	Ambiguous	-0.86	Ambiguous	-0.15	Likely Benign	0.281	Likely Benign	-2.06	Neutral	0.812	Possibly Damaging	0.251	Benign	3.52	Benign	0.18	Tolerated			0.1502	0.2196		1	1	-1.0	28.06
c.3161G>A	G1054D 2D AISynGAP1 missense variant G1054D is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.983019	Disordered	0.878015	Binding	0.389	0.936	0.875					Uncertain		1				-10.385	Likely Pathogenic	0.351	Ambiguous	Likely Benign										0.279	Likely Benign	-0.26	Neutral	0.818	Possibly Damaging	0.266	Benign	4.07	Benign	0.37	Tolerated	3.77	5	0.1824	0.2035		1	-1	-3.1	58.04
c.1222A>C	T408P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T408P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX, premPS, and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie and thus unavailable; Foldetta remains uncertain. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000											-10.384	Likely Pathogenic	0.230	Likely Benign	Likely Benign	1.08	Ambiguous	0.3	2.27	Destabilizing	1.68	Ambiguous	0.73	Ambiguous	0.323	Likely Benign	-4.19	Deleterious	0.998	Probably Damaging	0.963	Probably Damaging	4.07	Benign	0.05	Affected			0.1985	0.5779		0	-1	-0.9	-3.99
c.2005A>G	N669D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N669D has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, leans toward pathogenicity (3/4 votes). High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote) predicts pathogenic, and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of high‑confidence tools (AlphaMissense‑Optimized, Foldetta, and the SGM‑Consensus majority) suggest a pathogenic effect, but the presence of several benign predictions introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, which does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-10.384	Likely Pathogenic	0.674	Likely Pathogenic	Likely Benign	0.53	Ambiguous	0.2	0.00	Likely Benign	0.27	Likely Benign	1.00	Destabilizing	0.336	Likely Benign	-4.45	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	3.50	Benign	0.07	Tolerated			0.2182	0.2827		2	1	0.0	0.98
c.3749A>C	Q1250P 2D AIThe SynGAP1 missense variant Q1250P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. No Foldetta stability prediction is available for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-10.383	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.085	Likely Benign	-3.12	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.62	Benign	0.02	Affected			0.2376	0.4149		0	-1	1.9	-31.01
c.549T>A	H183Q 2D AIThe SynGAP1 missense variant H183Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.383	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.223	Likely Benign	-5.43	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.88	Benign	0.01	Affected			0.1470	0.3623		3	0	-0.3	-9.01
c.549T>G	H183Q 2D AIThe SynGAP1 missense variant H183Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.383	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.223	Likely Benign	-5.43	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.88	Benign	0.01	Affected			0.1470	0.3623		3	0	-0.3	-9.01
c.1612G>C	E538Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of evidence supports a benign impact. This conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-10.380	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	0.07	Likely Benign	0.0	0.07	Likely Benign	0.07	Likely Benign	-0.08	Likely Benign	0.188	Likely Benign	-2.14	Neutral	0.890	Possibly Damaging	0.436	Benign	3.37	Benign	0.11	Tolerated			0.1127	0.3952		2	2	0.0	-0.98
c.945C>A	N315K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. No other high‑accuracy tool provides a conclusive result. Overall, the majority of predictions (seven pathogenic vs. five benign, with two uncertain) indicate that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-10.380	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.1	0.08	Likely Benign	0.03	Likely Benign	0.87	Ambiguous	0.340	Likely Benign	-3.27	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.98	Pathogenic	0.54	Tolerated			0.2268	0.6436		1	0	-0.4	14.07
c.945C>G	N315K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315K is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence (seven pathogenic vs. five benign, with two uncertain) points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125											-10.380	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.1	0.08	Likely Benign	0.03	Likely Benign	0.87	Ambiguous	0.340	Likely Benign	-3.27	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.98	Pathogenic	0.54	Tolerated			0.2268	0.6436		1	0	-0.4	14.07
c.739C>A	Q247K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q247K (PH domain) is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are REVEL, polyPhen2_HumDiv, and ESM1b. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic). High‑accuracy methods all support benignity: AlphaMissense‑Optimized is benign, the SGM Consensus is benign, and Foldetta (combining FoldX‑MD and Rosetta) is benign. Uncertain results from AlphaMissense‑Default and Rosetta are treated as unavailable. Overall, the collective evidence points to a benign impact for Q247K, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.490133	Structured	0.283012	Uncertain	0.822	0.339	0.250											-10.377	Likely Pathogenic	0.502	Ambiguous	Likely Benign	-0.28	Likely Benign	0.1	0.74	Ambiguous	0.23	Likely Benign	-0.13	Likely Benign	0.529	Likely Pathogenic	-0.44	Neutral	0.787	Possibly Damaging	0.351	Benign	5.89	Benign	0.13	Tolerated			0.1366	0.2758		1	1	-0.4	0.04
c.3766G>A	D1256N 2D AIThe SynGAP1 D1256N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-10.375	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.0832	0.4219		2	1	0.0	-0.98
c.443C>T	P148L 2D AIThe SynGAP1 missense variant P148L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the consensus of the majority of tools points to a pathogenic effect. Because there is no ClinVar classification to contradict this, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-10.375	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.185	Likely Benign	-3.29	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.93	Benign	0.01	Affected			0.2229	0.5714		-3	-3	5.4	16.04
c.448C>G	L150V 2D AIThe SynGAP1 missense variant L150V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.375	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.84	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.1473	0.3178		2	1	0.4	-14.03
c.1762C>G	L588V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT classifies it as benign, whereas the remaining 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect for L588V. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-10.374	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	3.61	Destabilizing	0.4	2.81	Destabilizing	3.21	Destabilizing	1.24	Destabilizing	0.533	Likely Pathogenic	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.28	Pathogenic	0.08	Tolerated			0.1422	0.2228		2	1	0.4	-14.03
c.2162T>C	I721T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721T is not reported in ClinVar (ClinVar status: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that indicate a benign effect include only REVEL. All other evaluated tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote) yields Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts Pathogenic. No prediction or folding result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-10.374	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.73	Destabilizing	0.0	2.56	Destabilizing	2.65	Destabilizing	2.11	Destabilizing	0.417	Likely Benign	-4.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.0918	0.1019		0	-1	-5.2	-12.05
c.1343C>T	A448V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A448V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools (Rosetta and premPS) yield uncertain results. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates that A448V is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.292774	Uncertain	0.973	0.257	0.000											-10.372	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	3.31	Destabilizing	0.2	1.80	Ambiguous	2.56	Destabilizing	0.66	Ambiguous	0.487	Likely Benign	-3.95	Deleterious	0.998	Probably Damaging	0.955	Probably Damaging	3.26	Benign	0.02	Affected			0.0950	0.4955		0	0	2.4	28.05
c.1537T>C	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a deleterious effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No evidence from FoldX or Rosetta is considered decisive. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.674	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1539C>A	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a deleterious effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No evidence from FoldX or Rosetta is considered decisive. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.537	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1539C>G	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F513L missense variant has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is inconclusive and therefore not considered evidence. FoldX and Rosetta predictions are uncertain and treated as unavailable. Overall, the preponderance of evidence indicates that F513L is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.537	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1960G>C	E654Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E654Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of tools (nine benign vs. five pathogenic) suggest the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.368	Likely Pathogenic	0.699	Likely Pathogenic	Likely Benign	0.00	Likely Benign	0.0	0.18	Likely Benign	0.09	Likely Benign	-0.12	Likely Benign	0.298	Likely Benign	-2.79	Deleterious	0.244	Benign	0.075	Benign	3.33	Benign	0.02	Affected			0.1140	0.3913		2	2	0.0	-0.98
c.1477G>A	A493T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A493T missense variant is not reported in ClinVar and is absent from gnomAD. Consensus among most in silico predictors indicates a deleterious effect: REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, premPS, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as pathogenic or likely pathogenic. Only Rosetta predicts a benign outcome; FoldX, Foldetta, and AlphaMissense‑Optimized are uncertain or unavailable. High‑accuracy tools give the following: AlphaMissense‑Optimized – uncertain; SGM Consensus – likely pathogenic; Foldetta – uncertain. Taken together, the preponderance of evidence supports a pathogenic effect for A493T. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000											-10.366	Likely Pathogenic	0.892	Likely Pathogenic	Ambiguous	0.82	Ambiguous	0.0	0.39	Likely Benign	0.61	Ambiguous	1.10	Destabilizing	0.727	Likely Pathogenic	-3.41	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	-1.36	Pathogenic	0.04	Affected			0.0964	0.3972		1	0	-2.5	30.03
c.1319A>T	N440I 2D AISynGAP1 missense variant N440I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic; Foldetta remains inconclusive. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-10.365	Likely Pathogenic	0.778	Likely Pathogenic	Likely Benign	0.97	Ambiguous	0.9	1.10	Ambiguous	1.04	Ambiguous	0.10	Likely Benign	0.100	Likely Benign	-4.07	Deleterious	0.322	Benign	0.109	Benign	3.47	Benign	0.03	Affected			0.0554	0.3772		-2	-3	8.0	-0.94
c.2005A>C	N669H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669H has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-10.364	Likely Pathogenic	0.421	Ambiguous	Likely Benign	1.26	Ambiguous	0.2	1.69	Ambiguous	1.48	Ambiguous	0.80	Ambiguous	0.432	Likely Benign	-4.49	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.35	Benign	0.01	Affected			0.1732	0.4839		2	1	0.3	23.04
c.1458G>C	E486D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E486D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools are uncertain (premPS, AlphaMissense‑Optimized). High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Because the majority of standard predictors lean toward pathogenic and the SGM‑Consensus also indicates pathogenic, the variant is most likely pathogenic, although the Foldetta benign prediction and the presence of uncertain calls leave room for ambiguity. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.363	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	0.38	Likely Benign	0.29	Likely Benign	0.54	Ambiguous	0.166	Likely Benign	-2.58	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	3.43	Benign	0.16	Tolerated			0.1453	0.4115		3	2	0.0	-14.03
c.1458G>T	E486D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E486D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools are uncertain (premPS, AlphaMissense‑Optimized). High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Because the majority of standard predictors lean toward pathogenic and the SGM‑Consensus also indicates pathogenic, the variant is most likely pathogenic, although the Foldetta benign prediction and the presence of uncertain calls leave room for ambiguity. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.363	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	0.38	Likely Benign	0.29	Likely Benign	0.54	Ambiguous	0.166	Likely Benign	-2.58	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	3.43	Benign	0.16	Tolerated			0.1453	0.4115		3	2	0.0	-14.03
c.1702G>A	V568M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568M is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, whereas the remaining tools—REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the majority of evidence pointing to pathogenicity and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000											-10.361	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.06	Likely Benign	0.3	2.71	Destabilizing	1.39	Ambiguous	0.66	Ambiguous	0.811	Likely Pathogenic	-2.79	Deleterious	0.997	Probably Damaging	0.924	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.0697	0.3124		2	1	-2.3	32.06
c.2105A>C	Q702P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; FoldX is uncertain and therefore not counted. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, more tools predict pathogenicity (7) than benignity (5), and the high‑accuracy pathogenic prediction from Foldetta further supports this. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-10.361	Likely Pathogenic	0.324	Likely Benign	Likely Benign	1.76	Ambiguous	0.1	7.05	Destabilizing	4.41	Destabilizing	-0.04	Likely Benign	0.369	Likely Benign	-4.71	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.42	Benign	0.05	Affected			0.1877	0.3371		0	-1	1.9	-31.01
c.1943T>C	F648S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: benign calls are limited to SIFT and FATHMM, whereas the remaining 12 predictors—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, both polyPhen‑2 versions, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the substitution as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates a pathogenic effect. No prediction is inconclusive or missing. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-10.356	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.36	Destabilizing	0.0	3.23	Destabilizing	3.30	Destabilizing	1.35	Destabilizing	0.604	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.06	Tolerated			0.3680	0.0200		-3	-2	-3.6	-60.10
c.1308G>C	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1308G>T	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.3167G>A	G1056D 2D AIThe SynGAP1 missense variant G1056D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (six benign vs. three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988291	Disordered	0.868632	Binding	0.402	0.935	0.875											-10.352	Likely Pathogenic	0.328	Likely Benign	Likely Benign										0.380	Likely Benign	0.09	Neutral	0.666	Possibly Damaging	0.193	Benign	1.83	Pathogenic	0.92	Tolerated			0.1912	0.2626		1	-1	-3.1	58.04
c.1379A>T	K460M 2D 3DClick to see structure in 3D Viewer AISynGAP1 K460M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: FoldX and AlphaMissense‑Optimized. When high‑accuracy methods are considered separately, AlphaMissense‑Optimized remains inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-10.351	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.0	0.18	Likely Benign	0.40	Likely Benign	0.20	Likely Benign	0.252	Likely Benign	-4.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.29	Benign	0.02	Affected			0.1148	0.4522		0	-1	5.8	3.02
c.3710A>C	Y1237S 2D AIThe SynGAP1 missense variant Y1237S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic. The SGM‑Consensus, a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, therefore also predicts pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-10.349	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.463	Likely Benign	-7.21	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.5127	0.0891	Weaken	-3	-2	0.5	-76.10
c.1469C>T	A490V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A490V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly favor a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. No tool predicts a benign outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus remains likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the consensus of the majority of algorithms points to a pathogenic effect, and this conclusion does not conflict with the absence of ClinVar annotation. Thus, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125											-10.348	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.73	Ambiguous	0.3	0.62	Ambiguous	0.68	Ambiguous	0.69	Ambiguous	0.817	Likely Pathogenic	-3.93	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.26	Pathogenic	0.04	Affected			0.0983	0.4213		0	0	2.4	28.05
c.2011G>A	D671N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D671N is reported in gnomAD (6‑33441270‑G‑A) but has no ClinVar entry. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus remains pathogenic. Overall, the predictions are split, with a slight bias toward benign outcomes from the majority of tools, but the consensus pathogenic signal from SGM and several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of benign predictions, and this does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000								6-33441270-G-A			-10.347	Likely Pathogenic	0.685	Likely Pathogenic	Likely Benign	0.18	Likely Benign	0.1	0.39	Likely Benign	0.29	Likely Benign	0.19	Likely Benign	0.184	Likely Benign	-3.19	Deleterious	0.887	Possibly Damaging	0.592	Possibly Damaging	3.36	Benign	0.02	Affected	3.39	27	0.1298	0.6463		1	2	0.0	-0.98
c.439C>G	Q147E 2D AIThe SynGAP1 missense variant Q147E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy AlphaMissense‑Optimized result is unavailable, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie (2 pathogenic, 2 benign) and is therefore considered uncertain. Foldetta, which would assess protein‑folding stability, has no reported output for this variant, so its result is unavailable. Overall, the majority of evidence (five benign vs. three pathogenic) points to a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-10.347	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-1.47	Neutral	0.018	Benign	0.025	Benign	3.94	Benign	0.02	Affected			0.1561	0.1838		2	2	0.0	0.98
c.1693C>A	L565M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools, Rosetta and premPS, give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it is a 2‑vs‑2 split. No prediction or folding stability result is missing; the only unavailable result is the SGM Consensus. Overall, the balance of evidence (five benign vs four pathogenic predictions, with two high‑accuracy tools supporting benign) indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000											-10.346	Likely Pathogenic	0.666	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.1	0.51	Ambiguous	0.38	Likely Benign	0.69	Ambiguous	0.255	Likely Benign	-1.99	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.86	Benign	0.08	Tolerated			0.0934	0.2613		4	2	-1.9	18.03
c.2012A>G	D671G 2D AIThe SynGAP1 D671G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. No evidence from these tools contradicts the pathogenic prediction. Overall, the balance of evidence favors a pathogenic classification for D671G, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-10.346	Likely Pathogenic	0.857	Likely Pathogenic	Ambiguous	0.50	Ambiguous	0.5	1.53	Ambiguous	1.02	Ambiguous	0.00	Likely Benign	0.279	Likely Benign	-4.78	Deleterious	0.995	Probably Damaging	0.946	Probably Damaging	3.45	Benign	0.01	Affected			0.4032	0.5823		1	-1	3.1	-58.04
c.3173G>A	G1058D 2D AIThe SynGAP1 missense variant G1058D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443725‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.980739	Disordered	0.885724	Binding	0.407	0.929	0.875								6-33443725-G-A	1	6.21e-7	-10.344	Likely Pathogenic	0.391	Ambiguous	Likely Benign										0.177	Likely Benign	-0.33	Neutral	0.077	Benign	0.042	Benign	5.20	Benign	0.01	Affected	3.77	5	0.1889	0.2435		-1	1	-3.1	58.04
c.455G>A	R152Q 2D AIThe SynGAP1 missense variant R152Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33432752‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus remains unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no reported result for this variant. Overall, the preponderance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625					Uncertain		1	6-33432752-G-A	5	3.14e-6	-10.336	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-2.34	Neutral	0.997	Probably Damaging	0.968	Probably Damaging	3.89	Benign	0.00	Affected	3.61	5	0.3618	0.2996		1	1	1.0	-28.06
c.971G>T	R324L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R324L is catalogued in gnomAD (6-33437876‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, and SIFT; pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta (integrating FoldX‑MD and Rosetta outputs) reports a benign stability change. Overall, the majority of evidence points toward a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.257454	Structured	0.426893	Uncertain	0.954	0.397	0.000								6-33437876-G-T	1	6.20e-7	-10.328	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.28	Likely Benign	0.0	-0.08	Likely Benign	-0.18	Likely Benign	0.29	Likely Benign	0.489	Likely Benign	-2.20	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.86	Pathogenic	0.63	Tolerated	3.39	22	0.2310	0.5607		-2	-3	8.3	-43.03
c.1777C>G	L593V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L593V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Uncertain or inconclusive results come from Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic prediction; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of evidence (six pathogenic vs. four benign) points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-10.327	Likely Pathogenic	0.551	Ambiguous	Likely Benign	2.81	Destabilizing	0.2	1.10	Ambiguous	1.96	Ambiguous	1.39	Destabilizing	0.268	Likely Benign	-2.59	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.04	Benign	0.12	Tolerated			0.1599	0.3577		2	1	0.4	-14.03
c.2785A>T	N929Y 2D AIThe SynGAP1 missense variant N929Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL predicts benign, whereas the remaining eleven predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.327	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.391	Likely Benign	-6.02	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.0656	0.6489		-2	-2	2.2	49.07
c.1034T>G	L345R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L345R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict pathogenicity: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic prediction. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-10.325	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	0.96	Ambiguous	0.1	1.66	Ambiguous	1.31	Ambiguous	1.28	Destabilizing	0.247	Likely Benign	-3.98	Deleterious	0.993	Probably Damaging	0.796	Possibly Damaging	1.81	Pathogenic	0.04	Affected			0.1140	0.0685		-3	-2	-8.3	43.03
c.1433A>T	E478V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E478V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, Rosetta, polyPhen‑2 (HumDiv and HumVar), FATHMM, and premPS; pathogenic predictions from SGM‑Consensus, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: FoldX (uncertain) and AlphaMissense‑Optimized (uncertain). High‑accuracy assessments further split the signal: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. With six benign versus five pathogenic calls and no ClinVar evidence, the overall evidence slightly favors a benign interpretation, and there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-10.322	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	0.33	Likely Benign	0.44	Likely Benign	0.04	Likely Benign	0.385	Likely Benign	-5.84	Deleterious	0.434	Benign	0.199	Benign	3.35	Benign	0.01	Affected			0.0586	0.6604		-2	-2	7.7	-29.98
c.3368G>A	G1123D 2D AISynGAP1 missense variant G1123D is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33443920‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and ESM1b. AlphaMissense‑Default remains uncertain, and Foldetta stability analysis is unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus also benign, while Foldetta provides no result. Overall, the preponderance of evidence points to a benign effect, which does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.837511	Disordered	0.827246	Binding	0.346	0.934	0.875					Uncertain		2	6-33443920-G-A	2	1.33e-6	-10.321	Likely Pathogenic	0.405	Ambiguous	Likely Benign										0.360	Likely Benign	-0.78	Neutral	0.500	Possibly Damaging	0.157	Benign	4.34	Benign	0.19	Tolerated	3.77	5	0.1792	0.2035		1	-1	-3.1	58.04
c.979C>A	L327M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L327M missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, AlphaMissense‑Optimized, and Foldetta, whereas those that predict a pathogenic outcome are SGM‑Consensus, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta predicting a benign effect. Overall, the majority of tools indicate a pathogenic effect, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.409189	Uncertain	0.939	0.490	0.000											-10.320	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign	0.20	Likely Benign	0.0	0.72	Ambiguous	0.46	Likely Benign	1.07	Destabilizing	0.320	Likely Benign	-1.61	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	1.53	Pathogenic	0.01	Affected			0.0806	0.3807		4	2	-1.9	18.03
c.140G>C	R47P 2D AIThe SynGAP1 missense variant R47P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant and is likewise unavailable. High‑accuracy tools specifically indicate a benign prediction from AlphaMissense‑Optimized, while the other high‑accuracy methods (SGM Consensus, Foldetta) provide no definitive assessment. Overall, the balance of evidence (five pathogenic vs. four benign predictions) suggests the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125											-10.316	Likely Pathogenic	0.746	Likely Pathogenic	Likely Benign										0.195	Likely Benign	-1.63	Neutral	0.841	Possibly Damaging	0.809	Possibly Damaging	4.02	Benign	0.00	Affected			0.2050	0.4956		0	-2	2.9	-59.07
c.1608G>C	L536F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.316	Likely Pathogenic	0.851	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.5	0.40	Likely Benign	0.86	Ambiguous	0.70	Ambiguous	0.724	Likely Pathogenic	-3.90	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0874	0.2804		2	0	-1.0	34.02
c.1608G>T	L536F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only Rosetta. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.316	Likely Pathogenic	0.851	Likely Pathogenic	Ambiguous	1.31	Ambiguous	0.5	0.40	Likely Benign	0.86	Ambiguous	0.70	Ambiguous	0.722	Likely Pathogenic	-3.90	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0874	0.2804		2	0	-1.0	34.02
c.541C>A	H181N 2D AIThe SynGAP1 missense variant H181N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign prediction (2 benign vs. 1 pathogenic). Foldetta results are unavailable. Overall, the preponderance of evidence indicates that H181N is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500											-10.315	Likely Pathogenic	0.526	Ambiguous	Likely Benign										0.090	Likely Benign	-1.50	Neutral	0.421	Benign	0.107	Benign	4.18	Benign	0.05	Affected			0.1335	0.1839		2	1	-0.3	-23.04
c.1847A>G	D616G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results—FoldX, AlphaMissense‑Default, and Foldetta—are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the predictions are split evenly between benign and pathogenic, with no clear consensus. Thus, the variant is most likely of uncertain significance; it does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-10.310	Likely Pathogenic	0.547	Ambiguous	Likely Benign	1.48	Ambiguous	0.1	2.13	Destabilizing	1.81	Ambiguous	0.49	Likely Benign	0.144	Likely Benign	-5.60	Deleterious	0.985	Probably Damaging	0.800	Possibly Damaging	3.37	Benign	0.06	Tolerated			0.3496	0.4386		1	-1	3.1	-58.04
c.2183C>G	P728R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FoldX, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further indicate a likely pathogenic status from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and an uncertain outcome from Foldetta (combining FoldX‑MD and Rosetta). AlphaMissense‑Optimized also remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-10.309	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.59	Ambiguous	0.52	Ambiguous	0.70	Ambiguous	0.418	Likely Benign	-7.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1728	0.2865		0	-2	-2.9	59.07
c.563G>A	S188N 2D AIThe SynGAP1 missense variant S188N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of available predictions (five benign vs three pathogenic) suggest a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.307	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-2.34	Neutral	0.259	Benign	0.048	Benign	3.92	Benign	0.01	Affected			0.1420	0.5658		1	1	-2.7	27.03
c.3773A>T	Q1258L 2D AIThe SynGAP1 missense variant Q1258L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) predict pathogenic, while only one tool (REVEL) predicts benign. High‑accuracy assessments further support a deleterious effect: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, indicating no conflicting evidence from population databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.302	Likely Pathogenic	0.895	Likely Pathogenic	Ambiguous										0.341	Likely Benign	-5.55	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0448	0.4137		-2	-2	7.3	-14.97
c.632G>C	S211T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Two tools, FoldX and Rosetta, give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-10.301	Likely Pathogenic	0.678	Likely Pathogenic	Likely Benign	0.98	Ambiguous	0.5	-0.78	Ambiguous	0.10	Likely Benign	0.50	Likely Benign	0.157	Likely Benign	-2.33	Neutral	0.948	Possibly Damaging	0.484	Possibly Damaging	3.95	Benign	0.07	Tolerated			0.1678	0.5960		1	1	0.1	14.03
c.1897C>A	L633M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633M has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta is also inconclusive. Overall, the majority of definitive predictions (5 pathogenic vs. 4 benign) lean toward a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000											-10.300	Likely Pathogenic	0.718	Likely Pathogenic	Likely Benign	0.61	Ambiguous	0.1	1.47	Ambiguous	1.04	Ambiguous	0.90	Ambiguous	0.355	Likely Benign	-1.99	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.77	Benign	0.01	Affected			0.0984	0.2683		4	2	-1.9	18.03
c.3752A>T	Q1251L 2D AIThe SynGAP1 missense variant Q1251L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—favors pathogenicity. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-10.298	Likely Pathogenic	0.412	Ambiguous	Likely Benign										0.279	Likely Benign	-4.71	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.58	Benign	0.00	Affected			0.0626	0.4605		-2	-2	7.3	-14.97
c.1460A>G	N487S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N487S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is inconclusive, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is also inconclusive. Overall, the preponderance of evidence from multiple in silico predictors and the SGM Consensus indicates that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-10.297	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	1.42	Ambiguous	0.0	1.49	Ambiguous	1.46	Ambiguous	0.65	Ambiguous	0.459	Likely Benign	-4.97	Deleterious	0.999	Probably Damaging	0.979	Probably Damaging	2.74	Benign	0.01	Affected			0.3065	0.3656		1	1	2.7	-27.03
c.1562A>T	E521V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact for E521V, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-10.297	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.49	Likely Benign	0.40	Likely Benign	0.21	Likely Benign	0.413	Likely Benign	-5.15	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.05	Affected			0.0913	0.7104		-2	-2	7.7	-29.98
c.1985A>T	Q662L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen2_HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Overall, the majority of evidence supports a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-10.291	Likely Pathogenic	0.300	Likely Benign	Likely Benign	0.04	Likely Benign	0.0	0.12	Likely Benign	0.08	Likely Benign	0.17	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.699	Possibly Damaging	0.057	Benign	3.42	Benign	0.10	Tolerated			0.1070	0.5255		-2	-2	7.3	-14.97
c.772C>T	R258C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R258C missense variant is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33437677‑C‑T). Prediction tools that agree on a benign effect include only FATHMM. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—indicate a pathogenic or likely pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.295083	Structured	0.293667	Uncertain	0.894	0.260	0.250					Uncertain		1	6-33437677-C-T	1	6.20e-7	-10.285	Likely Pathogenic	0.790	Likely Pathogenic	Ambiguous	1.17	Ambiguous	0.4	1.76	Ambiguous	1.47	Ambiguous	0.87	Ambiguous	0.771	Likely Pathogenic	-6.79	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	5.77	Benign	0.00	Affected	3.39	15	0.3307	0.3411		-3	-4	7.0	-53.05
c.530T>C	F177S 2D AIThe SynGAP1 missense variant F177S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-10.283	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-2.58	Deleterious	0.596	Possibly Damaging	0.203	Benign	4.11	Benign	0.01	Affected			0.5034	0.1049	Weaken	-3	-2	-3.6	-60.10
c.602A>T	D201V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D201V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, while those that predict a pathogenic impact are SGM‑Consensus (Likely Pathogenic), Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. With the majority of tools indicating pathogenicity and no ClinVar record to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.428570	Uncertain	0.698	0.447	0.125											-10.283	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	0.87	Ambiguous	0.1	2.18	Destabilizing	1.53	Ambiguous	0.31	Likely Benign	0.305	Likely Benign	-5.01	Deleterious	0.999	Probably Damaging	0.946	Probably Damaging	4.04	Benign	0.02	Affected			0.0572	0.5207		-2	-3	7.7	-15.96
c.1631G>A	R544Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R544Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438874‑G‑A). Prediction tools that classify the change as benign include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is not contradictory to the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038858	Structured	0.016004	Uncertain	0.967	0.333	0.000					Uncertain		1	6-33438874-G-A	1	6.20e-7	-10.281	Likely Pathogenic	0.596	Likely Pathogenic	Likely Benign	0.19	Likely Benign	0.2	0.87	Ambiguous	0.53	Ambiguous	1.40	Destabilizing	0.542	Likely Pathogenic	-2.41	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.09	Tolerated	3.37	35	0.2103	0.1959		1	1	1.0	-28.06
c.902C>A	A301D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM all predict benign, whereas polyPhen‑2 (HumDiv and HumVar) and ESM1b predict pathogenic. Tools with uncertain outputs—Rosetta, Foldetta, and AlphaMissense‑Default—do not provide decisive evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign verdict; Foldetta remains inconclusive. Taken together, the preponderance of evidence indicates that A301D is most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-10.276	Likely Pathogenic	0.488	Ambiguous	Likely Benign	-0.37	Likely Benign	0.2	-1.15	Ambiguous	-0.76	Ambiguous	0.23	Likely Benign	0.224	Likely Benign	-0.35	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.17	Benign	0.07	Tolerated			0.1599	0.1705		0	-2	-5.3	44.01
c.1367A>T	Q456L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, with no evidence of contradiction with the ClinVar status. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-10.272	Likely Pathogenic	0.492	Ambiguous	Likely Benign	-0.88	Ambiguous	0.1	-0.30	Likely Benign	-0.59	Ambiguous	0.28	Likely Benign	0.347	Likely Benign	-6.65	Deleterious	0.987	Probably Damaging	0.914	Probably Damaging	3.49	Benign	0.36	Tolerated			0.0554	0.4317		-2	-2	7.3	-14.97
c.2036T>G	F679C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679C has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. FoldX and Foldetta are uncertain and are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta remains inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for F679C. This prediction is not contradicted by ClinVar status, which currently lacks any classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-10.269	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.65	Ambiguous	0.3	2.02	Destabilizing	1.84	Ambiguous	1.17	Destabilizing	0.532	Likely Pathogenic	-7.86	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.40	Benign	0.00	Affected			0.2344	0.0949		-4	-2	-0.3	-44.04
c.2123T>C	L708P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708P is not reported in ClinVar and is absent from gnomAD. Consensus among most in‑silico predictors is strongly pathogenic: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a deleterious effect. Only REVEL and FATHMM predict a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, SGM Consensus reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic change. Taken together, the preponderance of evidence points to a pathogenic impact for L708P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-10.268	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	4.29	Destabilizing	0.1	6.43	Destabilizing	5.36	Destabilizing	1.62	Destabilizing	0.298	Likely Benign	-4.47	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.39	Benign	0.04	Affected			0.2800	0.0825		-3	-3	-5.4	-16.04
c.1468G>A	A490T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490T is listed in gnomAD (variant ID 6‑33438500‑G‑A) but has no ClinVar entry. Prediction tools that agree on a pathogenic effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Tools that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. No tool predicts a benign outcome. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, while AlphaMissense‑Optimized remains uncertain and Foldetta is also uncertain. Based on the preponderance of pathogenic predictions and the lack of any benign calls, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125								6-33438500-G-A	1	6.20e-7	-10.266	Likely Pathogenic	0.892	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.2	1.70	Ambiguous	1.25	Ambiguous	1.00	Destabilizing	0.821	Likely Pathogenic	-3.87	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	-1.34	Pathogenic	0.03	Affected	3.37	35	0.1065	0.4495		0	1	-2.5	30.03
c.581A>T	E194V 2D AIThe SynGAP1 missense variant E194V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-10.261	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.284	Likely Benign	-4.67	Deleterious	0.580	Possibly Damaging	0.254	Benign	3.94	Benign	0.00	Affected			0.0623	0.5469		-2	-2	7.7	-29.98
c.1447A>C	I483L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign.” In contrast, polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic impact, and premPS remains uncertain. High‑accuracy assessments are uniformly benign: AlphaMissense‑Optimized is benign, the SGM‑Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Taken together, the majority of evidence, including the high‑accuracy tools, supports a benign classification for I483L. This conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.206376	Structured	0.415850	Uncertain	0.798	0.254	0.000											-10.258	Likely Pathogenic	0.332	Likely Benign	Likely Benign	0.31	Likely Benign	0.1	0.38	Likely Benign	0.35	Likely Benign	0.67	Ambiguous	0.341	Likely Benign	-1.86	Neutral	0.879	Possibly Damaging	0.970	Probably Damaging	4.09	Benign	0.31	Tolerated			0.0664	0.2461		2	2	-0.7	0.00
c.1447A>T	I483L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign.” In contrast, polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic impact, and premPS remains uncertain. High‑accuracy assessments are uniformly benign: AlphaMissense‑Optimized is benign, the SGM‑Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Taken together, the majority of evidence, including the high‑accuracy tools, supports a benign classification for I483L. This conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.206376	Structured	0.415850	Uncertain	0.798	0.254	0.000											-10.258	Likely Pathogenic	0.332	Likely Benign	Likely Benign	0.31	Likely Benign	0.1	0.38	Likely Benign	0.35	Likely Benign	0.67	Ambiguous	0.342	Likely Benign	-1.86	Neutral	0.879	Possibly Damaging	0.970	Probably Damaging	4.09	Benign	0.31	Tolerated			0.0664	0.2461		2	2	-0.7	0.00
c.514C>T	R172W 2D AIThe SynGAP1 missense variant R172W is listed in ClinVar (ID 996892.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33435156‑C‑T). Prediction tools that agree on a benign effect include REVEL and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic.” AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. High‑accuracy assessments therefore indicate a likely pathogenic outcome (SGM‑Consensus) with no definitive stabilizing‑folding evidence. Overall, the majority of computational predictions support a pathogenic classification, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375					Uncertain		2	6-33435156-C-T	9	5.58e-6	-10.258	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous										0.228	Likely Benign	-3.61	Deleterious	0.997	Probably Damaging	0.803	Possibly Damaging	3.95	Benign	0.00	Affected	3.61	5	0.1071	0.4065		2	-3	3.6	30.03
c.2842G>T	G948C 2D AIThe SynGAP1 missense variant G948C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar assertion exists for this variant. Thus, based on the available computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988505	Disordered	0.862121	Binding	0.365	0.919	0.750											-10.254	Likely Pathogenic	0.102	Likely Benign	Likely Benign										0.247	Likely Benign	-0.77	Neutral	0.997	Probably Damaging	0.840	Possibly Damaging	4.50	Benign	0.04	Affected			0.1422	0.4439		-3	-3	2.9	46.09
c.2138C>A	P713Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P713Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain calls are made by Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of evidence leans toward a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-10.253	Likely Pathogenic	0.875	Likely Pathogenic	Ambiguous	0.26	Likely Benign	0.0	-0.77	Ambiguous	-0.26	Likely Benign	0.95	Ambiguous	0.364	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.37	Benign	0.00	Affected			0.1225	0.3388		0	-1	-1.9	31.01
c.665T>C	V222A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V222A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity largely agree: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No predictions are missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.116183	Structured	0.402706	Uncertain	0.885	0.310	0.125											-10.248	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	2.89	Destabilizing	0.3	2.98	Destabilizing	2.94	Destabilizing	2.06	Destabilizing	0.894	Likely Pathogenic	-3.50	Deleterious	0.984	Probably Damaging	0.956	Probably Damaging	5.26	Benign	0.04	Affected			0.2386	0.2081		0	0	-2.4	-28.05
c.1294T>G	C432G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-10.247	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	1.37	Ambiguous	0.0	2.25	Destabilizing	1.81	Ambiguous	1.60	Destabilizing	0.631	Likely Pathogenic	-11.46	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.03	Affected			0.2796	0.2130		-3	-3	-2.9	-46.09
c.527G>T	S176I 2D AIThe SynGAP1 missense variant S176I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a 2‑vs‑2 split, and Foldetta results are not available. Overall, the majority of evidence (six benign predictions versus two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar, as the variant has no ClinVar entry. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.466016	Uncertain	0.380	0.597	0.375											-10.247	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.152	Likely Benign	-2.03	Neutral	0.002	Benign	0.003	Benign	4.04	Benign	0.06	Tolerated			0.0790	0.5290		-1	-2	5.3	26.08
c.588G>C	L196F 2D AIThe SynGAP1 missense variant L196F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-10.245	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.177	Likely Benign	-3.17	Deleterious	0.917	Possibly Damaging	0.502	Possibly Damaging	3.64	Benign	0.01	Affected			0.0557	0.2756		2	0	-1.0	34.02
c.588G>T	L196F 2D AIThe SynGAP1 missense variant L196F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-10.245	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.177	Likely Benign	-3.17	Deleterious	0.917	Possibly Damaging	0.502	Possibly Damaging	3.64	Benign	0.01	Affected			0.0557	0.2756		2	0	-1.0	34.02
c.730G>C	E244Q 2D AIThe SynGAP1 E244Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, six tools predict pathogenicity versus five predicting benignity, with no ClinVar evidence to contradict these findings. Thus, the variant is most likely pathogenic based on the current predictive landscape. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-10.245	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.9	-0.77	Ambiguous	-0.27	Likely Benign	0.40	Likely Benign	0.695	Likely Pathogenic	-2.49	Neutral	0.990	Probably Damaging	0.815	Possibly Damaging	5.78	Benign	0.05	Affected			0.1016	0.5610		2	2	0.0	-0.98
c.1520A>C	K507T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K507T missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifying it as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain result. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the absence of a ClinVar classification. **The variant is most likely pathogenic based on the current predictive evidence.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.244	Likely Pathogenic	0.468	Ambiguous	Likely Benign	0.82	Ambiguous	0.1	0.31	Likely Benign	0.57	Ambiguous	0.78	Ambiguous	0.724	Likely Pathogenic	-2.86	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.55	Pathogenic	0.12	Tolerated			0.1501	0.2451		0	-1	3.2	-27.07
c.1540A>C	I514L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I514L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools (premPS and AlphaMissense‑Default) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta also predicts a benign outcome. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.049374	Structured	0.221408	Uncertain	0.948	0.266	0.000											-10.239	Likely Pathogenic	0.490	Ambiguous	Likely Benign	-0.05	Likely Benign	0.2	0.34	Likely Benign	0.15	Likely Benign	0.81	Ambiguous	0.310	Likely Benign	-1.99	Neutral	0.879	Possibly Damaging	0.985	Probably Damaging	3.31	Benign	0.12	Tolerated			0.0767	0.2678		2	2	-0.7	0.00
c.1335G>C	E445D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445D is reported in gnomAD (ID 6‑33438240‑G‑C) but has no ClinVar entry. Functional prediction tools show a split verdict: benign calls come from REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence, especially the SGM Consensus, points to a pathogenic effect for E445D. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000								6-33438240-G-C	4	2.48e-6	-10.238	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.0	0.49	Likely Benign	0.65	Ambiguous	0.91	Ambiguous	0.136	Likely Benign	-2.86	Deleterious	0.977	Probably Damaging	0.921	Probably Damaging	3.54	Benign	0.09	Tolerated	3.38	31	0.1437	0.3526		2	3	0.0	-14.03
c.1335G>T	E445D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445D is not reported in ClinVar (status: none) and is absent from gnomAD. Prediction tools that agree on benign include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized; those that agree on pathogenic include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Foldetta, and premPS. High‑accuracy methods give a split view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta is uncertain. Overall, the predictions are inconclusive, with an equal number of benign and pathogenic calls. Thus, the variant is most likely benign based on the current evidence, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-10.238	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.0	0.49	Likely Benign	0.65	Ambiguous	0.91	Ambiguous	0.136	Likely Benign	-2.86	Deleterious	0.977	Probably Damaging	0.921	Probably Damaging	3.54	Benign	0.09	Tolerated	3.38	31	0.1437	0.3526		2	3	0.0	-14.03
c.470G>A	R157H 2D AIThe SynGAP1 missense variant R157H (ClinVar ID 2065231.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33432767‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the balance of predictions leans toward pathogenic, but the high‑accuracy tools do not provide a definitive verdict. This assessment does not contradict the ClinVar status, which remains Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.483068	Structured	0.523978	Binding	0.306	0.777	0.375					Uncertain		1	6-33432767-G-A	1	6.20e-7	-10.235	Likely Pathogenic	0.604	Likely Pathogenic	Likely Benign										0.254	Likely Benign	-2.23	Neutral	0.999	Probably Damaging	0.987	Probably Damaging	3.80	Benign	0.00	Affected	3.74	4	0.2981	0.1449		2	0	1.3	-19.05
c.2180A>T	N727I 2D 3DClick to see structure in 3D Viewer AISynGAP1 N727I is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, FoldX, premPS, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta provide inconclusive results. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts likely pathogenic, and Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.230	Likely Pathogenic	0.577	Likely Pathogenic	Likely Benign	0.17	Likely Benign	0.1	0.90	Ambiguous	0.54	Ambiguous	0.43	Likely Benign	0.319	Likely Benign	-5.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.13	Pathogenic	0.03	Affected			0.0666	0.5917		-2	-3	8.0	-0.94
c.3593A>G	Y1198C 2D AIThe SynGAP1 missense variant Y1198C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-10.230	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.370	Likely Benign	-6.07	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.43	Pathogenic	0.07	Tolerated			0.3335	0.1312		0	-2	3.8	-60.04
c.899C>T	S300F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S300F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. The remaining tool, AlphaMissense‑Default, gives an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward pathogenicity, while two high‑accuracy methods support a benign effect. Thus, the variant is most likely pathogenic based on the current computational evidence, which does not contradict its ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.356642	Structured	0.256848	Uncertain	0.742	0.280	0.375					Uncertain		1				-10.222	Likely Pathogenic	0.353	Ambiguous	Likely Benign	-0.29	Likely Benign	0.4	0.16	Likely Benign	-0.07	Likely Benign	0.04	Likely Benign	0.117	Likely Benign	-2.66	Deleterious	0.975	Probably Damaging	0.596	Possibly Damaging	1.52	Pathogenic	0.01	Affected	3.47	19	0.0579	0.5701		-3	-2	3.6	60.10	233.6	-67.6	-0.1	0.0	0.4	0.2	X	X						Potentially Pathogenic	The hydroxyl group of the Ser300 side chain, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Met289-Pro298, res. Thr305-Asn315), hydrogen bonds with the guanidinium group of Arg299 and the backbone amide group and side chain of Ser302. Thus, in the WT simulations, it contributes to the β hairpin stability. In the variant simulations, the phenol ring of Phe300 cannot form any side chain-related hydrogen bonds, and Arg299 is moved away from its central hairpin loop position.β hairpins are potential nucleation sites during the initial stages of protein folding, so even minor changes in them could be significant. Due to its location near the membrane surface, the residue swap could also affect the C2 loop dynamics and SynGAP-membrane association. However, this is beyond the scope of the solvent-only simulations to unravel.
c.1370G>A	S457N 2D AIThe SynGAP1 missense variant S457N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, Rosetta, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give a mixed picture: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the majority of individual predictors lean toward pathogenicity, but the high‑accuracy Foldetta result suggests a benign impact. Thus, the variant is most likely pathogenic based on the preponderance of predictions, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000					Uncertain		1				-10.221	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	-0.22	Likely Benign	-0.02	Likely Benign	0.67	Ambiguous	0.241	Likely Benign	-2.76	Deleterious	0.940	Possibly Damaging	0.843	Possibly Damaging	3.28	Benign	0.06	Tolerated			0.1015	0.4980		1	1	-2.7	27.03
c.1516C>G	L506V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM Consensus) all indicate a pathogenic impact. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-10.220	Likely Pathogenic	0.512	Ambiguous	Likely Benign	2.61	Destabilizing	0.2	3.27	Destabilizing	2.94	Destabilizing	1.36	Destabilizing	0.420	Likely Benign	-2.98	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	1.62	Pathogenic	0.04	Affected			0.1126	0.1660		2	1	0.4	-14.03
c.1760G>A	R587K 2D 3DClick to see structure in 3D Viewer AISynGAP1 R587K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from SIFT and AlphaMissense‑Optimized, and pathogenic predictions from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus prediction but contradicts the benign calls from SIFT and AlphaMissense‑Optimized. Thus, the variant is most likely pathogenic, and this conclusion aligns with the lack of ClinVar annotation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.077330	Uncertain	0.862	0.216	0.000											-10.220	Likely Pathogenic	0.433	Ambiguous	Likely Benign	0.63	Ambiguous	0.1	1.14	Ambiguous	0.89	Ambiguous	0.88	Ambiguous	0.539	Likely Pathogenic	-2.55	Deleterious	0.967	Probably Damaging	0.955	Probably Damaging	-1.16	Pathogenic	0.07	Tolerated			0.5313	0.3897	Weaken	3	2	0.6	-28.01
c.1036G>A	V346M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V346M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FoldX, whereas the majority of other in silico methods (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, PROVEAN, AlphaMissense‑Optimized, and the SGM‑Consensus score) indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-10.218	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.1	2.52	Destabilizing	1.41	Ambiguous	0.67	Ambiguous	0.367	Likely Benign	-2.72	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.05	Affected			0.1050	0.4749		2	1	-2.3	32.06
c.3713A>G	Q1238R 2D AIThe SynGAP1 missense variant Q1238R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Consensus from standard predictors shows a split: benign calls come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment gives AlphaMissense‑Optimized benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the ClinVar status, which currently contains no assertion for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-10.216	Likely Pathogenic	0.477	Ambiguous	Likely Benign										0.229	Likely Benign	-2.29	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	2.40	Pathogenic	0.04	Affected			0.1165	0.2019		1	1	-1.0	28.06
c.2150T>C	L717P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) all classify the variant as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-10.214	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.96	Destabilizing	0.2	6.56	Destabilizing	5.26	Destabilizing	1.66	Destabilizing	0.447	Likely Benign	-5.32	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.28	Benign	0.00	Affected			0.3065	0.1053		-3	-3	-5.4	-16.04
c.529T>A	F177I 2D AIThe SynGAP1 missense variant F177I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. three pathogenic) suggest a benign impact, though the presence of pathogenic signals from high‑accuracy tools introduces uncertainty. The variant is most likely benign based on the current evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-10.208	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.148	Likely Benign	-0.60	Neutral	0.131	Benign	0.058	Benign	4.18	Benign	0.11	Tolerated			0.2282	0.3299		1	0	1.7	-34.02
c.1442A>C	H481P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H481P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM. Those that predict a pathogenic effect comprise SGM Consensus (Likely Pathogenic), PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and PROVEAN. Tools with inconclusive results are Foldetta (Uncertain) and premPS (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta remains uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-10.205	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.3	3.69	Destabilizing	1.61	Ambiguous	0.67	Ambiguous	0.385	Likely Benign	-5.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.26	Tolerated			0.1979	0.3553		0	-2	1.6	-40.02
c.723A>C	K241N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.198	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.13	Ambiguous	1.03	Ambiguous	0.89	Ambiguous	0.663	Likely Pathogenic	-4.23	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.81	Benign	0.03	Affected			0.3426	0.1872		1	0	0.4	-14.07
c.723A>T	K241N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS and are not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.198	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.13	Ambiguous	1.03	Ambiguous	0.89	Ambiguous	0.663	Likely Pathogenic	-4.23	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.81	Benign	0.03	Affected			0.3426	0.1872		1	0	0.4	-14.07
c.167T>G	L56R 2D AIThe SynGAP1 missense variant L56R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (5 pathogenic vs 3 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-10.194	Likely Pathogenic	0.918	Likely Pathogenic	Ambiguous										0.264	Likely Benign	-1.92	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.79	Benign	0.00	Affected			0.1191	0.0685		-3	-2	-8.3	43.03
c.650A>T	E217V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E217V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include Rosetta, FATHMM, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). FoldX and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E217V. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.278302	Structured	0.404912	Uncertain	0.823	0.284	0.000											-10.194	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.76	Ambiguous	0.6	0.39	Likely Benign	0.58	Ambiguous	0.23	Likely Benign	0.723	Likely Pathogenic	-4.84	Deleterious	0.900	Possibly Damaging	0.461	Possibly Damaging	5.79	Benign	0.03	Affected			0.0919	0.8340		-2	-2	7.7	-29.98
c.1505G>C	G502A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G502A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from Foldetta, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, and premPS. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized indicates a benign effect, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—concludes pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact for G502A, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000											-10.191	Likely Pathogenic	0.607	Likely Pathogenic	Likely Benign	0.82	Ambiguous	0.4	-0.53	Ambiguous	0.15	Likely Benign	0.54	Ambiguous	0.725	Likely Pathogenic	-5.64	Deleterious	0.512	Possibly Damaging	0.157	Benign	-1.59	Pathogenic	0.17	Tolerated			0.3548	0.3393		1	0	2.2	14.03
c.1678G>C	V560L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V560L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Optimized, and Foldetta; pathogenic predictions come from polyPhen‑2 HumDiv, ESM1b, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the bulk of evidence points to a benign effect, but the SGM Consensus and the presence of pathogenic signals from several high‑confidence tools introduce uncertainty. Thus, the variant is most likely benign based on the prevailing predictions, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.021381	Structured	0.013872	Uncertain	0.853	0.204	0.000											-10.191	Likely Pathogenic	0.533	Ambiguous	Likely Benign	-0.44	Likely Benign	0.0	0.48	Likely Benign	0.02	Likely Benign	0.45	Likely Benign	0.489	Likely Benign	-2.45	Neutral	0.508	Possibly Damaging	0.209	Benign	-1.24	Pathogenic	0.40	Tolerated	3.37	35	0.1430	0.4162		1	2	-0.4	14.03
c.1678G>T	V560L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V560L variant has no ClinVar entry (ClinVar status: None) but is catalogued in gnomAD (ID 6‑33440730‑G‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, ESM1b, and FATHMM (polyPhen‑2 HumVar is benign, AlphaMissense‑Default is uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning pathogenic (2 pathogenic vs 1 benign), and Foldetta indicating a benign stability change. Overall, the majority of conventional tools favor a benign classification, yet the high‑accuracy consensus and Foldetta suggest a pathogenic signal. Based on the most reliable predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.021381	Structured	0.013872	Uncertain	0.853	0.204	0.000								6-33440730-G-T	1	6.34e-7	-10.191	Likely Pathogenic	0.533	Ambiguous	Likely Benign	-0.44	Likely Benign	0.0	0.48	Likely Benign	0.02	Likely Benign	0.45	Likely Benign	0.489	Likely Benign	-2.45	Neutral	0.508	Possibly Damaging	0.209	Benign	-1.24	Pathogenic	0.40	Tolerated	3.37	35	0.1430	0.4162		1	2	-0.4	14.03
c.849G>C	E283D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E283D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and SIFT, whereas pathogenic predictions are made by AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and FoldX. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic. The Foldetta stability analysis is inconclusive and therefore treated as unavailable. Overall, the majority of evidence points to a pathogenic effect for E283D, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-10.190	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.25	Destabilizing	0.2	0.94	Ambiguous	1.60	Ambiguous	0.60	Ambiguous	0.280	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.63	Pathogenic	0.06	Tolerated			0.2008	0.3480		3	2	0.0	-14.03
c.849G>T	E283D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and FoldX. Predictions that remain inconclusive are Foldetta, Rosetta, and premPS. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta’s stability analysis is uncertain. Overall, the preponderance of evidence indicates that E283D is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000											-10.190	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.25	Destabilizing	0.2	0.94	Ambiguous	1.60	Ambiguous	0.60	Ambiguous	0.280	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.63	Pathogenic	0.06	Tolerated			0.2008	0.3480		3	2	0.0	-14.03
c.986G>T	R329L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R329L has no ClinVar entry and is not reported in gnomAD. Consensus from standard prediction tools shows a split: benign calls come from REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar, while pathogenic calls arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked uncertain (Rosetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the majority of tools lean toward pathogenicity, but the folding‑stability evidence suggests a benign effect. Given the lack of ClinVar annotation, there is no contradiction. The variant is most likely pathogenic based on the preponderance of pathogenic predictions, though the benign folding‑stability result introduces uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-10.186	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	-0.09	Likely Benign	0.4	0.53	Ambiguous	0.22	Likely Benign	0.54	Ambiguous	0.219	Likely Benign	-4.81	Deleterious	0.653	Possibly Damaging	0.361	Benign	4.02	Benign	0.01	Affected			0.1827	0.4121		-3	-2	8.3	-43.03
c.2102C>T	P701L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P701L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and ESM1b. The remaining tools (FoldX, Rosetta, AlphaMissense‑Default) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (7 benign vs. 3 pathogenic) and the two high‑accuracy benign calls suggest that the variant is most likely benign. This conclusion does not contradict any ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000											-10.185	Likely Pathogenic	0.515	Ambiguous	Likely Benign	1.15	Ambiguous	0.0	-0.68	Ambiguous	0.24	Likely Benign	0.12	Likely Benign	0.116	Likely Benign	-3.04	Deleterious	0.642	Possibly Damaging	0.087	Benign	3.50	Benign	0.09	Tolerated			0.2018	0.5546		-3	-3	5.4	16.04
c.1692G>C	E564D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT, whereas a majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-10.184	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	1.13	Ambiguous	0.80	Ambiguous	0.26	Likely Benign	0.637	Likely Pathogenic	-2.75	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.1431	0.3354		3	2	0.0	-14.03
c.1692G>T	E564D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT, whereas a majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-10.184	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	1.13	Ambiguous	0.80	Ambiguous	0.26	Likely Benign	0.637	Likely Pathogenic	-2.75	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.1431	0.3354		3	2	0.0	-14.03
c.3719G>T	R1240L 2D AIThe SynGAP1 missense variant R1240L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, R1240L is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-10.181	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic										0.372	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.1513	0.3394		-3	-2	8.3	-43.03
c.3754C>G	Q1252E 2D AIThe SynGAP1 missense variant Q1252E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. three benign) lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-10.181	Likely Pathogenic	0.485	Ambiguous	Likely Benign										0.152	Likely Benign	-2.32	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.01	Pathogenic	0.00	Affected			0.1130	0.1266		2	2	0.0	0.98
c.755C>T	P252L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P252L missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign are premPS and FATHMM, while the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic effect. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore do not contribute to the overall assessment. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-10.181	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.93	Ambiguous	0.0	1.56	Ambiguous	1.25	Ambiguous	0.47	Likely Benign	0.794	Likely Pathogenic	-9.19	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	5.81	Benign	0.00	Affected			0.2027	0.6475		-3	-3	5.4	16.04
c.1480A>C	I494L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I494L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence (five pathogenic versus four benign predictions, with several uncertain calls) leans toward a pathogenic interpretation. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000											-10.175	Likely Pathogenic	0.478	Ambiguous	Likely Benign	0.28	Likely Benign	0.1	1.11	Ambiguous	0.70	Ambiguous	0.91	Ambiguous	0.513	Likely Pathogenic	-1.69	Neutral	0.645	Possibly Damaging	0.718	Possibly Damaging	-0.88	Pathogenic	0.11	Tolerated			0.0816	0.2851		2	2	-0.7	0.00
c.1480A>T	I494L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I494L variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta indicating uncertain stability change. Overall, the balance of evidence leans toward pathogenicity, with a majority of tools and the SGM Consensus supporting a deleterious effect. This conclusion does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000											-10.175	Likely Pathogenic	0.478	Ambiguous	Likely Benign	0.28	Likely Benign	0.1	1.11	Ambiguous	0.70	Ambiguous	0.91	Ambiguous	0.513	Likely Pathogenic	-1.69	Neutral	0.645	Possibly Damaging	0.718	Possibly Damaging	-0.88	Pathogenic	0.11	Tolerated			0.0816	0.2851		2	2	-0.7	0.00
c.1141G>T	G381W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G381W is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438046‑G‑T). Prediction tools that agree on a benign effect include premPS, PROVEAN, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments give AlphaMissense‑Optimized a benign call, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) a pathogenic call, and Foldetta (combining FoldX‑MD and Rosetta outputs) a pathogenic call. No prediction or folding result is missing or inconclusive. Overall, the majority of tools and the high‑accuracy methods indicate a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750								6-33438046-G-T	1	6.24e-7	-10.173	Likely Pathogenic	0.438	Ambiguous	Likely Benign	8.81	Destabilizing	2.0	3.17	Destabilizing	5.99	Destabilizing	0.02	Likely Benign	0.576	Likely Pathogenic	-1.04	Neutral	0.996	Probably Damaging	0.920	Probably Damaging	1.31	Pathogenic	0.01	Affected	4.32	9	0.0993	0.4000		-2	-7	-0.5	129.16
c.1789T>C	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is listed in ClinVar with an uncertain significance (ClinVar ID 3658115.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only SIFT, whereas the remaining tools—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. The high‑accuracy AlphaMissense‑Optimized score is pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for F597L, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000					Uncertain		1				-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	0.929	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			0.2232	0.2596		2	0	1.0	-34.02
c.1791C>A	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: the benign group contains only SIFT, while the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta are inconclusive, providing no definitive evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a damaging effect, SGM‑Consensus concurs with a likely pathogenic classification, and Foldetta remains uncertain. Taken together, the overwhelming majority of predictions indicate a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	0.879	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			0.2232	0.2596		2	0	1.0	-34.02
c.1791C>G	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: the benign group contains only SIFT, while the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta are inconclusive, providing no definitive evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a damaging effect, SGM‑Consensus concurs with a likely pathogenic classification, and Foldetta remains uncertain. Taken together, the overwhelming majority of predictions indicate a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	0.879	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			0.2232	0.2596		2	0	1.0	-34.02
c.919T>C	F307L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized and the SGM Consensus both indicate a likely pathogenic effect, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the bulk of evidence points to a pathogenic impact, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-10.173	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	0.14	Likely Benign	0.34	Likely Benign	0.57	Ambiguous	0.597	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.01	Affected			0.2800	0.4207		2	0	1.0	-34.02
c.921C>A	F307L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized and the SGM Consensus both indicate a likely pathogenic effect, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the bulk of evidence points to a pathogenic impact, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-10.173	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	0.14	Likely Benign	0.34	Likely Benign	0.57	Ambiguous	0.529	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.01	Affected			0.2800	0.4207		2	0	1.0	-34.02
c.921C>G	F307L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta and Foldetta, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the change as pathogenic. Uncertain results are reported by FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the consensus of the majority of tools points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-10.173	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	0.14	Likely Benign	0.34	Likely Benign	0.57	Ambiguous	0.529	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.01	Affected			0.2800	0.4207		2	0	1.0	-34.02
c.1825G>A	G609R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G609R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Predictions that remain uncertain are Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated tools (eight pathogenic vs. three benign) predict a pathogenic impact for G609R. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.203786	Uncertain	0.851	0.252	0.000											-10.172	Likely Pathogenic	0.543	Ambiguous	Likely Benign	2.09	Destabilizing	0.1	0.37	Likely Benign	1.23	Ambiguous	0.60	Ambiguous	0.520	Likely Pathogenic	-2.68	Deleterious	0.974	Probably Damaging	0.818	Possibly Damaging	-1.41	Pathogenic	0.07	Tolerated			0.1158	0.4348		-3	-2	-4.1	99.14
c.1825G>C	G609R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G609R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Predictions that remain uncertain are Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated tools (eight pathogenic vs. three benign) predict a pathogenic impact for G609R. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.203786	Uncertain	0.851	0.252	0.000											-10.172	Likely Pathogenic	0.543	Ambiguous	Likely Benign	2.09	Destabilizing	0.1	0.37	Likely Benign	1.23	Ambiguous	0.60	Ambiguous	0.520	Likely Pathogenic	-2.68	Deleterious	0.974	Probably Damaging	0.818	Possibly Damaging	-1.41	Pathogenic	0.07	Tolerated			0.1158	0.4348		-3	-2	-4.1	99.14
c.859G>A	D287N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D287N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default). Two tools give uncertain results (Rosetta, AlphaMissense‑Optimized). High‑accuracy assessments further separate the evidence: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign impact. Overall, the majority of conventional predictors lean toward pathogenicity, while the most accurate stability‑based method suggests benign. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000											-10.167	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.16	Likely Benign	0.3	-0.54	Ambiguous	-0.19	Likely Benign	0.05	Likely Benign	0.372	Likely Benign	-4.60	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.06	Tolerated			0.1338	0.8194		2	1	0.0	-0.98
c.2027G>T	S676I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and ESM1b. FoldX, Rosetta, Foldetta, and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the balance of evidence (five benign versus three pathogenic predictions) indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-10.165	Likely Pathogenic	0.383	Ambiguous	Likely Benign	1.25	Ambiguous	0.3	1.12	Ambiguous	1.19	Ambiguous	0.14	Likely Benign	0.170	Likely Benign	-2.46	Neutral	0.801	Possibly Damaging	0.063	Benign	3.38	Benign	0.02	Affected			0.0879	0.5720		-1	-2	5.3	26.08
c.1147G>T	G383W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G383W is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438052‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as benign, and Foldetta as pathogenic. Because the majority of conventional predictors favor pathogenicity while the high‑accuracy subset is split, the overall evidence leans toward a pathogenic interpretation. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.728858	Disordered	0.429104	Uncertain	0.296	0.949	0.750					Uncertain		1	6-33438052-G-T	1	6.22e-7	-10.161	Likely Pathogenic	0.439	Ambiguous	Likely Benign	5.81	Destabilizing	3.6	4.44	Destabilizing	5.13	Destabilizing	0.08	Likely Benign	0.469	Likely Benign	-1.01	Neutral	0.959	Probably Damaging	0.704	Possibly Damaging	4.09	Benign	0.00	Affected	4.32	7	0.0972	0.3785		-2	-7	-0.5	129.16
c.3617A>C	K1206T 2D AIThe SynGAP1 missense variant K1206T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206T. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-10.161	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.40	Pathogenic	0.01	Affected			0.1913	0.3354		0	-1	3.2	-27.07
c.1277A>T	N426I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426I has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and the protein‑folding stability method Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicting pathogenicity, and Foldetta indicating a benign folding stability outcome. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-10.158	Likely Pathogenic	0.570	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.0	0.14	Likely Benign	0.41	Likely Benign	0.23	Likely Benign	0.216	Likely Benign	-5.71	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.31	Benign	0.09	Tolerated			0.0656	0.3244		-2	-3	8.0	-0.94
c.3761A>G	E1254G 2D AIThe SynGAP1 missense variant E1254G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized indicates a benign change, but the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the SGM Consensus suggests that the variant is most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-10.156	Likely Pathogenic	0.706	Likely Pathogenic	Likely Benign										0.315	Likely Benign	-4.52	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.34	Pathogenic	0.01	Affected			0.2636	0.5072		0	-2	3.1	-72.06
c.1651C>G	L551V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools give uncertain results: AlphaMissense‑Default and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic impact for L551V. This conclusion does not contradict ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000											-10.154	Likely Pathogenic	0.556	Ambiguous	Likely Benign	2.04	Destabilizing	0.0	1.41	Ambiguous	1.73	Ambiguous	1.03	Destabilizing	0.575	Likely Pathogenic	-1.39	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	-1.48	Pathogenic	0.22	Tolerated			0.1376	0.2778		2	1	0.4	-14.03
c.986G>A	R329H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R329H is listed in ClinVar with an uncertain significance (ClinVar ID 2074400.0) and is present in gnomAD (ID 6‑33437891‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the balance of predictions favors a pathogenic impact, which does not contradict the ClinVar uncertain status but suggests the variant is more likely deleterious. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250					Uncertain		1	6-33437891-G-A	2	1.24e-6	-10.154	Likely Pathogenic	0.769	Likely Pathogenic	Likely Benign	2.53	Destabilizing	0.7	0.71	Ambiguous	1.62	Ambiguous	0.82	Ambiguous	0.155	Likely Benign	-3.17	Deleterious	0.995	Probably Damaging	0.778	Possibly Damaging	4.04	Benign	0.05	Affected	3.41	15	0.2955	0.1961		2	0	1.3	-19.05	220.4	81.4	0.1	0.1	0.2	0.3								Uncertain	The guanidinium group of Arg329, located at the end of an anti-parallel β sheet strand (res. Ala322-Asp330), faces the negatively charged lipid bilayer surface. While the residue swap does not cause any apparent negative effects on the protein structure in the variant simulations, it could adversely affect the SynGAP-membrane association in reality. The positively charged Arg329 side chain forms hydrogen bonds with other loop residues (e.g., Ser371, Asp338) that are expected to dynamically interact with the membrane head group region. However, this phenomenon is beyond the scope of the solvent-only simulations to unravel. Notably, histidine can also be double protonated and positively charged, but this alternative protonation state was not considered in the variant simulations.
c.647A>G	Q216R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q216R is not reported in ClinVar and has no gnomAD entry. Prediction tools that call the variant benign include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while pathogenic calls come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as Benign. Overall, the predictions are split, with a slight edge toward pathogenicity. The variant is therefore most likely pathogenic based on the current computational evidence, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.149	Likely Pathogenic	0.821	Likely Pathogenic	Ambiguous	-0.42	Likely Benign	0.0	0.09	Likely Benign	-0.17	Likely Benign	-0.01	Likely Benign	0.513	Likely Pathogenic	-2.70	Deleterious	0.963	Probably Damaging	0.549	Possibly Damaging	6.00	Benign	0.19	Tolerated			0.1972	0.2748		1	1	-1.0	28.06
c.1040C>T	T347I 2D 3DClick to see structure in 3D Viewer AISynGAP1 T347I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that provide definitive calls cluster into two groups: benign predictions come from REVEL, premPS, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Tools with inconclusive outputs (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) are treated as unavailable. High‑accuracy assessments further split the evidence: AlphaMissense‑Optimized predicts benign, while the SGM consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenic; Foldetta remains uncertain. Consequently, the variant’s pathogenicity is ambiguous, with an equal number of strong benign and pathogenic calls and no consensus from the most reliable methods. The variant is therefore most likely uncertain, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.268042	Structured	0.349915	Uncertain	0.951	0.434	0.000											-10.148	Likely Pathogenic	0.387	Ambiguous	Likely Benign	-0.79	Ambiguous	0.1	-0.94	Ambiguous	-0.87	Ambiguous	0.29	Likely Benign	0.079	Likely Benign	-3.12	Deleterious	0.627	Possibly Damaging	0.139	Benign	1.70	Pathogenic	0.08	Tolerated			0.0885	0.6298		0	-1	5.2	12.05
c.961C>A	R321S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools—FoldX and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125											-10.146	Likely Pathogenic	0.497	Ambiguous	Likely Benign	0.66	Ambiguous	0.1	-0.30	Likely Benign	0.18	Likely Benign	0.24	Likely Benign	0.379	Likely Benign	-2.27	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.00	Pathogenic	0.10	Tolerated			0.2958	0.2785		0	-1	3.7	-69.11
c.1930G>T	D644Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 D644Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. The remaining tools, FoldX, REVEL, premPS, polyPhen‑2 HumVar, and FATHMM, support a benign effect, while PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default support a pathogenic effect. Overall, the majority of evidence leans toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-10.143	Likely Pathogenic	0.721	Likely Pathogenic	Likely Benign	0.03	Likely Benign	0.1	-1.18	Ambiguous	-0.58	Ambiguous	-0.04	Likely Benign	0.318	Likely Benign	-4.93	Deleterious	0.968	Probably Damaging	0.311	Benign	3.44	Benign	0.02	Affected			0.0679	0.6094		-4	-3	2.2	48.09
c.889A>G	K297E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; the only inconclusive result is FoldX, which is listed as “Uncertain” and is treated as unavailable. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, K297E is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-10.143	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.99	Ambiguous	0.4	2.43	Destabilizing	2.21	Destabilizing	1.16	Destabilizing	0.507	Likely Pathogenic	-3.54	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.61	Pathogenic	0.02	Affected			0.4073	0.1547		0	1	0.4	0.94
c.568A>C	S190R 2D AIThe SynGAP1 missense variant S190R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority of the four high‑accuracy tools) also predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250											-10.137	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-2.92	Deleterious	0.917	Possibly Damaging	0.446	Benign	4.07	Benign	0.04	Affected			0.0809	0.4059		0	-1	-3.7	69.11
c.570C>A	S190R 2D AIThe SynGAP1 missense variant S190R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority of the four high‑accuracy tools) also predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250											-10.137	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.92	Deleterious	0.917	Possibly Damaging	0.446	Benign	4.07	Benign	0.04	Affected			0.0809	0.4059		0	-1	-3.7	69.11
c.570C>G	S190R 2D AIThe SynGAP1 missense variant S190R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250											-10.137	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.92	Deleterious	0.917	Possibly Damaging	0.446	Benign	4.07	Benign	0.04	Affected			0.0809	0.4059		0	-1	-3.7	69.11
c.1742G>T	R581L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R581L is not reported in ClinVar and is present in gnomAD (ID 6‑33440794‑G‑T). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas tools that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. In contrast, the Foldetta stability assessment, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of computational evidence supports a pathogenic classification for R581L, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.029544	Uncertain	0.829	0.236	0.000								6-33440794-G-T	3	1.86e-6	-10.134	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.1	-0.20	Likely Benign	0.05	Likely Benign	0.45	Likely Benign	0.654	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.33	Pathogenic	0.08	Tolerated	3.37	34	0.1550	0.3483		-2	-3	8.3	-43.03
c.566C>T	P189L 2D AIThe SynGAP1 missense variant P189L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic classification, with no ClinVar record to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250											-10.132	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-7.28	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	4.04	Benign	0.17	Tolerated			0.2283	0.7378		-3	-3	5.4	16.04
c.3794G>C	R1265T 2D AIThe SynGAP1 missense variant R1265T is reported in ClinVar as Pathogenic (ClinVar ID 522047.0) and is not found in gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions supports a pathogenic classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000					Likely Pathogenic		1				-10.129	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.529	Likely Pathogenic	-4.97	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.29	Pathogenic	0.00	Affected	3.77	5	0.1947	0.4618		-1	-1	3.8	-55.08
c.701G>C	R234P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R234P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, whereas the majority of evaluated algorithms (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.311558	Uncertain	0.804	0.322	0.000											-10.126	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	1.33	Ambiguous	0.6	1.36	Ambiguous	1.35	Ambiguous	0.13	Likely Benign	0.826	Likely Pathogenic	-4.43	Deleterious	0.929	Possibly Damaging	0.519	Possibly Damaging	5.93	Benign	0.04	Affected			0.1972	0.4336		0	-2	2.9	-59.07
c.1606T>A	L536M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L536M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, PROVEAN, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-10.124	Likely Pathogenic	0.462	Ambiguous	Likely Benign	0.37	Likely Benign	0.1	1.18	Ambiguous	0.78	Ambiguous	0.93	Ambiguous	0.571	Likely Pathogenic	-1.94	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	-1.32	Pathogenic	0.01	Affected			0.0937	0.3299		4	2	-1.9	18.03
c.1447A>G	I483V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I483V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Predictions marked as uncertain include FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, whereas Foldetta remains uncertain. Overall, the balance of evidence from both general and high‑accuracy tools leans toward a benign effect, which does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.206376	Structured	0.415850	Uncertain	0.798	0.254	0.000					Conflicting		2				-10.121	Likely Pathogenic	0.523	Ambiguous	Likely Benign	1.00	Ambiguous	0.0	0.27	Likely Benign	0.64	Ambiguous	1.02	Destabilizing	0.228	Likely Benign	-0.86	Neutral	0.914	Possibly Damaging	0.921	Probably Damaging	3.23	Benign	0.03	Affected	3.37	32	0.0876	0.2691		3	4	-0.3	-14.03
c.1752C>G	I584M 2D 3DClick to see structure in 3D Viewer AISynGAP1 I584M is listed in ClinVar (ID 1301269) with an uncertain significance designation and is present in gnomAD (variant ID 6‑33440804‑C‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of individual predictors lean toward a benign outcome, with two high‑accuracy tools supporting benign and one supporting pathogenic. Thus, the variant is most likely benign, which is consistent with its ClinVar uncertain status and does not contradict that classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000					Uncertain		3	6-33440804-C-G	1	6.20e-7	-10.119	Likely Pathogenic	0.419	Ambiguous	Likely Benign	0.11	Likely Benign	0.1	0.46	Likely Benign	0.29	Likely Benign	1.16	Destabilizing	0.478	Likely Benign	-2.62	Deleterious	0.983	Probably Damaging	0.925	Probably Damaging	-1.25	Pathogenic	0.12	Tolerated	3.37	34	0.0777	0.2127		2	1	-2.6	18.03	247.5	-20.3	-0.1	0.3	-0.1	0.1						X		Potentially Benign	A hydrophobic residue, Ile584, located in an α helix (res. Glu582-Met603), is swapped for another hydrophobic residue, Met584. The sec-butyl hydrocarbon side chain of Ile584 packs hydrophobically with residues in an inter-helix hydrophobic space (e.g., Leu588, Met477, Val473, and Ile483).In the variant simulations, the thioether hydrophobic side chain of Met584 maintains similar interactions as Ile584 in the WT, as it is roughly the same size and fits well within the hydrophobic space. Thus, the residue swap does not appear to cause any negative effects on the protein structure.
c.641T>A	L214Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change at residue 214 (Leu→Gln) is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, the majority (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect, while only FATHMM predicts a benign outcome. Three tools (FoldX, Rosetta, Foldetta) return uncertain results. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta is uncertain. Taken together, the overwhelming consensus of pathogenic predictions indicates that the variant is most likely pathogenic, with no ClinVar evidence contradicting this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-10.119	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.60	Ambiguous	0.6	1.71	Ambiguous	1.66	Ambiguous	1.73	Destabilizing	0.912	Likely Pathogenic	-5.12	Deleterious	0.997	Probably Damaging	0.936	Probably Damaging	5.74	Benign	0.00	Affected			0.1140	0.0930		-2	-2	-7.3	14.97
c.932A>T	H311L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H311L missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include AlphaMissense‑Optimized, Foldetta, premPS, and Rosetta. Tools that predict a pathogenic outcome are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta predicting a benign effect. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125											-10.119	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.53	Ambiguous	0.0	-0.04	Likely Benign	-0.29	Likely Benign	0.43	Likely Benign	0.663	Likely Pathogenic	-7.99	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.87	Pathogenic	0.02	Affected			0.0961	0.5292		-2	-3	7.0	-23.98
c.448C>A	L150I 2D AIThe SynGAP1 missense variant L150I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a likely pathogenic impact for the variant. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.118	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous										0.080	Likely Benign	-1.25	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.0894	0.3468		2	2	0.7	0.00
c.1320T>A	N440K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. The remaining methods—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—yield uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-10.114	Likely Pathogenic	0.895	Likely Pathogenic	Ambiguous	0.92	Ambiguous	0.1	1.04	Ambiguous	0.98	Ambiguous	0.40	Likely Benign	0.058	Likely Benign	-1.97	Neutral	0.206	Benign	0.021	Benign	3.50	Benign	0.19	Tolerated			0.1660	0.2550		1	0	-0.4	14.07
c.1320T>G	N440K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. The remaining methods—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—yield uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-10.114	Likely Pathogenic	0.895	Likely Pathogenic	Ambiguous	0.92	Ambiguous	0.1	1.04	Ambiguous	0.98	Ambiguous	0.40	Likely Benign	0.057	Likely Benign	-1.97	Neutral	0.206	Benign	0.021	Benign	3.50	Benign	0.19	Tolerated			0.1660	0.2550		1	0	-0.4	14.07
c.562A>G	S188G 2D AIThe SynGAP1 missense variant S188G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is “Likely Pathogenic.” AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.113	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-3.10	Deleterious	0.882	Possibly Damaging	0.404	Benign	3.91	Benign	0.00	Affected			0.3045	0.5542		1	0	0.4	-30.03
c.1064G>T	G355V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G355V is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or unavailable results are reported for FoldX, premPS, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-10.111	Likely Pathogenic	0.675	Likely Pathogenic	Likely Benign	1.78	Ambiguous	0.6	0.14	Likely Benign	0.96	Ambiguous	0.53	Ambiguous	0.346	Likely Benign	-7.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.78	Pathogenic	0.04	Affected			0.1221	0.4685		-1	-3	4.6	42.08
c.890A>C	K297T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K297T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none, whereas those that predict a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods specifically show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-10.110	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.1	1.19	Ambiguous	1.37	Ambiguous	0.59	Ambiguous	0.551	Likely Pathogenic	-5.28	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.62	Pathogenic	0.01	Affected			0.2294	0.4024		0	-1	3.2	-27.07
c.1426T>C	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.196	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1428C>A	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.180	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1428C>G	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438460‑C‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that returned uncertain results—FoldX, Rosetta, Foldetta, and premPS—do not contribute to the assessment. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, with two pathogenic and two benign calls; Foldetta also reports an uncertain stability change. Overall, the balance of evidence favors a pathogenic effect for F476L, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000					Uncertain		2	6-33438460-C-G	4	2.48e-6	-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.180	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.2179A>T	N727Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727Y has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Two tools remain inconclusive: AlphaMissense‑Default and Rosetta. Separately, the high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of individual predictors and the SGM Consensus lean toward a pathogenic interpretation, while the high‑accuracy folding‑stability assessment is benign. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.106	Likely Pathogenic	0.426	Ambiguous	Likely Benign	-0.12	Likely Benign	0.1	-0.52	Ambiguous	-0.32	Likely Benign	0.35	Likely Benign	0.347	Likely Benign	-5.34	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.12	Pathogenic	0.02	Affected			0.0563	0.6091		-2	-2	2.2	49.07
c.1756G>C	D586H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586H missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from premPS and SIFT, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all indicate pathogenicity. The high‑accuracy methods reinforce this trend: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, as there is no conflicting status to contradict the prediction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-10.104	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.3	0.89	Ambiguous	0.95	Ambiguous	0.26	Likely Benign	0.672	Likely Pathogenic	-3.44	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.23	Pathogenic	0.17	Tolerated			0.1307	0.5558		1	-1	0.3	22.05
c.419C>G	S140C 2D AIThe SynGAP1 missense variant S140C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the S140C variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-10.103	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-3.11	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	3.49	Benign	0.01	Affected			0.0811	0.5709		0	-1	3.3	16.06
c.1993T>G	Y665D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665D is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as Uncertain. No evidence from these tools contradicts the ClinVar status, which is currently unreported. Overall, the balance of evidence—seven pathogenic versus four benign predictions, with a pathogenic consensus from SGM‑Consensus—suggests the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-10.101	Likely Pathogenic	0.737	Likely Pathogenic	Likely Benign	1.15	Ambiguous	0.2	1.30	Ambiguous	1.23	Ambiguous	0.15	Likely Benign	0.227	Likely Benign	-3.67	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	1.00	Tolerated			0.3838	0.0573		-4	-3	-2.2	-48.09
c.3779A>C	K1260T 2D AIThe SynGAP1 missense variant K1260T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in‑silico tools indicates that K1260T is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.099	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign										0.387	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1859	0.3028		0	-1	3.2	-27.07
c.508C>G	R170G 2D AIThe SynGAP1 missense variant R170G is not reported in ClinVar and has no entries in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact for R170G, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-10.092	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-3.19	Deleterious	0.664	Possibly Damaging	0.137	Benign	3.88	Benign	0.00	Affected			0.3285	0.3004		-3	-2	4.1	-99.14
c.2176A>T	R726W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726W has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of tools (seven) predict a benign effect, but the SGM‑Consensus and several high‑accuracy methods indicate pathogenicity, leaving the variant’s clinical significance uncertain. The predictions do not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-10.091	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	0.46	Likely Benign	0.1	0.46	Likely Benign	0.46	Likely Benign	0.15	Likely Benign	0.217	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.57	Benign	0.01	Affected			0.1161	0.4252		2	-3	3.6	30.03
c.3601G>A	E1201K 2D AIThe SynGAP1 missense variant E1201K is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that E1201K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-10.090	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.437	Likely Benign	-3.27	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.63	Pathogenic	0.02	Affected			0.1539	0.5812		0	1	-0.4	-0.94
c.953C>T	P318L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P318L is listed in ClinVar with an uncertain significance (ClinVar ID 956570.0) and is present in gnomAD (6‑33437858‑C‑T). Functional prediction tools that agree on a benign effect are Rosetta and premPS. The remaining tools—REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Taken together, the preponderance of evidence points to a pathogenic effect for P318L, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000					Uncertain		3	6-33437858-C-T	3	1.86e-6	-10.090	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.33	Ambiguous	0.1	0.26	Likely Benign	0.80	Ambiguous	0.43	Likely Benign	0.624	Likely Pathogenic	-8.96	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.82	Pathogenic	0.03	Affected	3.38	23	0.2166	0.6941		-3	-3	5.4	16.04	228.6	-68.9	-0.7	0.7	-0.4	0.1						X		Potentially Benign	The cyclic five-membered pyrrolidine ring of Pro318, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Asp330-Ala322, res. Thr305-Asn315), packs against the hydrophobic side chain of Ile205 at the end of the anti-parallel β sheet in the PH domain. In the variant simulations, the iso-butyl side chain of Leu318 is unable to do the same, potentially weakening the PH and C2 domain association. Importantly, the residue swap could also affect loop formation during folding, as proline can make tighter turns than leucine. Because the residue swap could affect the C2 domain stability, it could also negatively impact the SynGAP-membrane association.
c.488T>A	F163Y 2D AIThe SynGAP1 missense variant F163Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign) and is therefore treated as unavailable. High‑accuracy methods show AlphaMissense‑Optimized as benign; Foldetta results are not provided, so its stability prediction is unavailable. Overall, the majority of available predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-10.087	Likely Pathogenic	0.722	Likely Pathogenic	Likely Benign										0.125	Likely Benign	-1.09	Neutral	0.981	Probably Damaging	0.931	Probably Damaging	4.03	Benign	0.04	Affected			0.1529	0.2152		7	3	-4.1	16.00
c.1363C>A	L455M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L455M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and Foldetta is uncertain. No folding‑stability method provides a definitive result. Consequently, the computational evidence does not favor either benign or pathogenic classification. The variant’s status is therefore inconclusive, and this lack of consensus does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.188120	Structured	0.310377	Uncertain	0.963	0.168	0.000											-10.086	Likely Pathogenic	0.802	Likely Pathogenic	Ambiguous	0.88	Ambiguous	0.0	1.27	Ambiguous	1.08	Ambiguous	0.59	Ambiguous	0.147	Likely Benign	-1.64	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.25	Benign	0.11	Tolerated			0.0606	0.3362		4	2	-1.9	18.03
c.1739G>A	G580D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580D is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while premPS and Rosetta are uncertain. High‑accuracy tools reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No benign predictions are present. Consequently, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-10.086	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.1	1.39	Ambiguous	2.12	Destabilizing	0.83	Ambiguous	0.712	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.25	Pathogenic	0.04	Affected			0.1793	0.1971		1	-1	-3.1	58.04
c.1809G>A	M603I 2D AIThe SynGAP1 missense variant M603I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include Rosetta, Foldetta, and premPS, whereas the majority of tools predict it to be pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX reports an uncertain effect. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence points to a pathogenic effect for M603I, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-10.086	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.6	0.07	Likely Benign	0.44	Likely Benign	-0.07	Likely Benign	0.699	Likely Pathogenic	-3.32	Deleterious	0.833	Possibly Damaging	0.886	Possibly Damaging	-1.21	Pathogenic	0.03	Affected			0.1208	0.2350		2	1	2.6	-18.03
c.1809G>C	M603I 2D AIThe SynGAP1 missense variant M603I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX reports an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for M603I. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-10.086	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.6	0.07	Likely Benign	0.44	Likely Benign	-0.07	Likely Benign	0.699	Likely Pathogenic	-3.32	Deleterious	0.833	Possibly Damaging	0.886	Possibly Damaging	-1.21	Pathogenic	0.03	Affected			0.1208	0.2350		2	1	2.6	-18.03
c.1809G>T	M603I 2D AIThe SynGAP1 missense variant M603I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX reports an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for M603I. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-10.086	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.6	0.07	Likely Benign	0.44	Likely Benign	-0.07	Likely Benign	0.698	Likely Pathogenic	-3.32	Deleterious	0.833	Possibly Damaging	0.886	Possibly Damaging	-1.21	Pathogenic	0.03	Affected			0.1208	0.2350		2	1	2.6	-18.03
c.2107C>G	L703V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Because the variant is not present in ClinVar or gnomAD, there is no existing clinical classification to contradict. Overall, the majority of predictions and the two high‑accuracy benign assessments suggest the variant is most likely benign, although the Foldetta result indicates a potential pathogenic effect that warrants further functional investigation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.086	Likely Pathogenic	0.301	Likely Benign	Likely Benign	2.32	Destabilizing	0.1	2.61	Destabilizing	2.47	Destabilizing	1.07	Destabilizing	0.080	Likely Benign	-2.22	Neutral	0.789	Possibly Damaging	0.352	Benign	3.19	Benign	0.00	Affected			0.1383	0.2621		2	1	0.4	-14.03
c.1813C>G	P605A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic, while premPS remains uncertain. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenic. No tool predicts a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000											-10.085	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.58	Destabilizing	0.3	2.42	Destabilizing	2.50	Destabilizing	0.91	Ambiguous	0.744	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.75	Pathogenic	0.00	Affected			0.3432	0.4607		1	-1	3.4	-26.04
c.652T>G	F218V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; pathogenic predictions arise from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus agrees on a likely pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenicity. No predictions or stability results are missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion aligns with the absence of a ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000											-10.081	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	4.18	Destabilizing	0.2	6.35	Destabilizing	5.27	Destabilizing	1.15	Destabilizing	0.691	Likely Pathogenic	-4.14	Deleterious	0.300	Benign	0.066	Benign	5.81	Benign	0.08	Tolerated			0.2173	0.2258		-1	-1	1.4	-48.04
c.485G>C	R162P 2D AISynGAP1 missense variant R162P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool reports an uncertain result, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, which combines FoldX‑MD and Rosetta stability outputs, has no available result for this variant. Consequently, the evidence is evenly divided: four tools support benign, four support pathogenic, and the remaining high‑accuracy methods provide no decisive signal. The variant is therefore not clearly benign or pathogenic based on current predictions, and this lack of consensus does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250											-10.077	Likely Pathogenic	0.787	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-1.50	Neutral	0.910	Possibly Damaging	0.578	Possibly Damaging	4.03	Benign	0.30	Tolerated			0.2192	0.5507		0	-2	2.9	-59.07
c.3724G>A	E1242K 2D AIThe SynGAP1 missense variant E1242K is catalogued in gnomAD (6‑33446716‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicting REVEL score contrasts with a pathogenic consensus from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic,” and the protein‑folding stability method Foldetta is not available for this variant. Taken together, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.557691	Disordered	0.456349	Uncertain	0.870	0.549	0.500								6-33446716-G-A	1	6.20e-7	-10.075	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous										0.179	Likely Benign	-3.13	Deleterious	0.939	Possibly Damaging	0.670	Possibly Damaging	2.22	Pathogenic	0.00	Affected	3.77	5	0.1520	0.4024		1	0	-0.4	-0.94
c.1753G>A	A585T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A585T is reported in gnomAD (ID 6‑33440805‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, PROVEAN, and SIFT, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic effect for A585T. This conclusion is not contradicted by ClinVar, which contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000								6-33440805-G-A	13	8.05e-6	-10.063	Likely Pathogenic	0.876	Likely Pathogenic	Ambiguous	1.66	Ambiguous	0.2	1.97	Ambiguous	1.82	Ambiguous	0.23	Likely Benign	0.465	Likely Benign	-1.73	Neutral	1.000	Probably Damaging	0.994	Probably Damaging	-1.30	Pathogenic	0.26	Tolerated	3.37	35	0.1132	0.4212		0	1	-2.5	30.03
c.1016A>C	K339T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339T missense variant is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools are split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic calls are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further highlight this discordance: the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect, whereas Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign impact. AlphaMissense‑Optimized returned an uncertain result and is treated as unavailable. Overall, the majority of robust predictors lean toward pathogenicity, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-10.061	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.0	0.10	Likely Benign	0.21	Likely Benign	-0.04	Likely Benign	0.512	Likely Pathogenic	-4.73	Deleterious	0.991	Probably Damaging	0.795	Possibly Damaging	1.94	Pathogenic	0.10	Tolerated			0.1900	0.3020		0	-1	3.2	-27.07
c.461G>T	S154I 2D AIThe SynGAP1 missense variant S154I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not provided and is treated as unavailable. High‑accuracy predictions therefore indicate a benign outcome (AlphaMissense‑Optimized) with no decisive evidence from SGM Consensus or Foldetta. Overall, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-10.061	Likely Pathogenic	0.665	Likely Pathogenic	Likely Benign										0.105	Likely Benign	-2.24	Neutral	0.990	Probably Damaging	0.797	Possibly Damaging	4.03	Benign	0.07	Tolerated			0.0953	0.5123		-1	-2	5.3	26.08
c.3776T>C	I1259T 2D AIThe SynGAP1 missense variant I1259T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign) and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) points to a pathogenic impact. The variant is most likely pathogenic based on current predictions, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.057	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.399	Likely Benign	-2.47	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.54	Benign	0.01	Affected			0.0991	0.1051		0	-1	-5.2	-12.05
c.1391T>A	F464Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464Y is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta provide uncertain results and are treated as unavailable evidence. Overall, the balance of evidence points to a pathogenic effect for F464Y, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.056	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.35	Ambiguous	0.1	0.24	Likely Benign	0.80	Ambiguous	1.31	Destabilizing	0.387	Likely Benign	-2.98	Deleterious	0.979	Probably Damaging	0.953	Probably Damaging	3.28	Benign	0.01	Affected			0.1081	0.1523		7	3	-4.1	16.00
c.1568A>C	N523T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The premPS score is uncertain and does not contribute to the consensus. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding result is missing or inconclusive. Overall, the majority of tools (10/14) predict pathogenicity, whereas four predict benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-10.056	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.47	Likely Benign	0.2	-0.22	Likely Benign	0.13	Likely Benign	0.65	Ambiguous	0.646	Likely Pathogenic	-5.33	Deleterious	0.898	Possibly Damaging	0.592	Possibly Damaging	-1.40	Pathogenic	0.02	Affected			0.0920	0.3780		0	0	2.8	-13.00
c.2522T>G	V841G 2D AIThe SynGAP1 missense variant V841G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, whereas the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for V841G, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-10.054	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.288	Likely Benign	-4.11	Deleterious	0.997	Probably Damaging	0.999	Probably Damaging	2.51	Benign	0.00	Affected			0.2351	0.2422		-1	-3	-4.6	-42.08
c.1565A>G	E522G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522G missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as deleterious. No tool reports a benign outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a damaging effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta’s stability analysis is inconclusive. FoldX, Rosetta, and premPS are uncertain and are treated as unavailable evidence. Overall, the computational evidence overwhelmingly points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.053	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.0	1.62	Ambiguous	1.17	Ambiguous	0.58	Ambiguous	0.823	Likely Pathogenic	-6.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.34	Pathogenic	0.01	Affected			0.2672	0.3654		0	-2	3.1	-72.06
c.571A>C	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.324	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.573T>A	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.573T>G	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.2131C>G	L711V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L711V is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441596‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000					Uncertain		1	6-33441596-C-G	1	6.20e-7	-10.045	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	3.48	Destabilizing	0.1	2.22	Destabilizing	2.85	Destabilizing	1.40	Destabilizing	0.170	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.34	Benign	0.00	Affected	3.50	9	0.1318	0.3010		1	2	0.4	-14.03
c.2787C>A	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2787C>G	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.1910C>G	S637C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, FoldX, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-10.040	Likely Pathogenic	0.138	Likely Benign	Likely Benign	0.25	Likely Benign	0.0	0.54	Ambiguous	0.40	Likely Benign	0.22	Likely Benign	0.169	Likely Benign	-2.83	Deleterious	0.985	Probably Damaging	0.533	Possibly Damaging	3.34	Benign	0.01	Affected			0.1327	0.4439		0	-1	3.3	16.06
c.1591T>G	C531G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX and AlphaMissense‑Optimized, while the majority of other in silico predictors (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) indicate a pathogenic impact. Uncertain results come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the balance of evidence leans toward pathogenicity, with no ClinVar entry to contradict this assessment. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-10.037	Likely Pathogenic	0.577	Likely Pathogenic	Likely Benign	0.47	Likely Benign	0.3	1.49	Ambiguous	0.98	Ambiguous	1.42	Destabilizing	0.545	Likely Pathogenic	-9.76	Deleterious	0.985	Probably Damaging	0.832	Possibly Damaging	-1.24	Pathogenic	0.00	Affected			0.2653	0.2297		-3	-3	-2.9	-46.09
c.1481T>C	I494T 2D AIThe SynGAP1 missense variant I494T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions are missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000											-10.033	Likely Pathogenic	0.754	Likely Pathogenic	Likely Benign	2.45	Destabilizing	0.7	2.12	Destabilizing	2.29	Destabilizing	1.73	Destabilizing	0.907	Likely Pathogenic	-4.61	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	-1.38	Pathogenic	0.01	Affected			0.1003	0.0640		0	-1	-5.2	-12.05
c.1952A>T	E651V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E651V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools split in their assessment: benign‑predicted scores include REVEL, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic‑predicted scores come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX give uncertain results. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, leans pathogenic (3 pathogenic vs. 1 benign); Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the majority of tools (including the high‑accuracy SGM Consensus) suggest a pathogenic impact, whereas Foldetta and several other predictors indicate benign. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-10.025	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous	0.63	Ambiguous	0.1	0.25	Likely Benign	0.44	Likely Benign	0.21	Likely Benign	0.467	Likely Benign	-5.53	Deleterious	0.988	Probably Damaging	0.734	Possibly Damaging	3.27	Benign	0.05	Affected			0.0824	0.6136		-2	-2	7.7	-29.98
c.961C>T	R321C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33437866‑C‑T). Prediction tools that agree on a benign effect include REVEL, premPS, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Five tools (SGM‑Consensus, FoldX, Rosetta, AlphaMissense‑Default, and Foldetta) report uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (six out of eleven) support a pathogenic impact, while three support benign and five are inconclusive. Thus, the variant is most likely pathogenic based on current computational evidence, and this does not contradict its ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125					Conflicting		2	6-33437866-C-T	9	5.58e-6	-10.025	Likely Pathogenic	0.387	Ambiguous	Likely Benign	0.57	Ambiguous	0.1	0.56	Ambiguous	0.57	Ambiguous	0.18	Likely Benign	0.495	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.89	Pathogenic	0.01	Affected	3.38	23	0.3313	0.2516		-3	-4	7.0	-53.05
c.3796C>G	L1266V 2D AIThe SynGAP1 missense variant L1266V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-10.024	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.53	Deleterious	0.995	Probably Damaging	0.890	Possibly Damaging	2.16	Pathogenic	0.00	Affected			0.1301	0.3118		2	1	0.4	-14.03
c.1223C>T	T408I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T408I missense variant is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438128‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Tools with uncertain or mixed outputs are AlphaMissense‑Default and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points toward a benign effect, and this conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000								6-33438128-C-T	1	6.19e-7	-10.023	Likely Pathogenic	0.542	Ambiguous	Likely Benign	-0.16	Likely Benign	0.1	-0.67	Ambiguous	-0.42	Likely Benign	0.38	Likely Benign	0.131	Likely Benign	-4.53	Deleterious	0.976	Probably Damaging	0.607	Possibly Damaging	4.08	Benign	0.05	Affected	3.38	28	0.0905	0.6700		-1	0	5.2	12.05
c.2045A>G	Y682C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682C is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, while only FATHMM predicts a benign outcome. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) are uncertain. High‑accuracy assessments reinforce this trend: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; AlphaMissense‑Optimized is uncertain; and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic impact for Y682C. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-10.023	Likely Pathogenic	0.793	Likely Pathogenic	Ambiguous	1.79	Ambiguous	0.1	1.51	Ambiguous	1.65	Ambiguous	1.11	Destabilizing	0.559	Likely Pathogenic	-8.71	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.33	Benign	0.01	Affected			0.2949	0.2399		0	-2	3.8	-60.04
c.1538T>A	F513Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT classifies it as benign, whereas REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenicity. Stability‑based methods (FoldX, Rosetta, Foldetta) and AlphaMissense‑Optimized return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as uncertain. With 10 of 12 evaluated tools indicating pathogenicity and no conflicting ClinVar annotation, the variant is most likely pathogenic, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.022	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	1.09	Ambiguous	0.2	1.03	Ambiguous	1.06	Ambiguous	1.09	Destabilizing	0.791	Likely Pathogenic	-2.92	Deleterious	0.988	Probably Damaging	0.976	Probably Damaging	-1.39	Pathogenic	0.07	Tolerated			0.1046	0.1087		7	3	-4.1	16.00
c.2089T>A	W697R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic effect: SGM‑Consensus, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, and premPS. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple pathogenic‑predicting tools indicates that W697R is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-10.020	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.14	Ambiguous	0.1	1.18	Ambiguous	1.16	Ambiguous	1.25	Destabilizing	0.401	Likely Benign	-9.50	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.45	Benign	0.02	Affected	3.46	13	0.3944	0.0612		2	-3	-3.6	-30.03	254.4	-41.2	0.0	0.0	-0.7	0.0						X		Potentially Benign	The indole ring of Trp697, located on the outer surface of an α-helix (res. Leu685-Val699), is not involved in any long-lasting interactions in the WT simulations. In the variant simulations, the positively charged guanidinium side chain of Arg697 occasionally forms hydrogen bonds with nearby residues, such as Ser722 and Asn719. However, similar to Trp697 in the WT, Arg697 does not form any long-lasting interactions and thus does not induce any negative structural effects in the simulations.
c.2089T>C	W697R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697R is listed in ClinVar as Benign (ClinVar ID 703213.0) and is present in the gnomAD database (gnomAD ID 6‑33441348‑T‑C). Functional prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple pathogenic‑predicting tools suggests that the variant is most likely pathogenic, which contradicts its current ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000					Likely Benign		1	6-33441348-T-C	1	6.20e-7	-10.020	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.14	Ambiguous	0.1	1.18	Ambiguous	1.16	Ambiguous	1.25	Destabilizing	0.401	Likely Benign	-9.50	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.45	Benign	0.02	Affected	3.46	13	0.3944	0.0612		2	-3	-3.6	-30.03	254.4	-41.2	0.0	0.0	-0.7	0.0						X		Potentially Benign	The indole ring of Trp697, located on the outer surface of an α-helix (res. Leu685-Val699), is not involved in any long-lasting interactions in the WT simulations. In the variant simulations, the positively charged guanidinium side chain of Arg697 occasionally forms hydrogen bonds with nearby residues, such as Ser722 and Asn719. However, similar to Trp697 in the WT, Arg697 does not form any long-lasting interactions and thus does not induce any negative structural effects in the simulations.
c.1668C>A	N556K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556K is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, premPS, and SIFT, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions support a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-10.017	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	0.510	Likely Pathogenic	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			0.2024	0.2240		1	0	-0.4	14.07
c.1668C>G	N556K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from FoldX, Rosetta, premPS, and SIFT; pathogenic predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation (i.e., no conflicting benign classification). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000											-10.017	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	0.510	Likely Pathogenic	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			0.2024	0.2240		1	0	-0.4	14.07
c.1810T>G	S604A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S604A has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain and does not contribute to a consensus. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With two of the three high‑accuracy tools indicating benign and no ClinVar evidence to contradict, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.192527	Uncertain	0.911	0.195	0.000											-10.017	Likely Pathogenic	0.608	Likely Pathogenic	Likely Benign	0.02	Likely Benign	0.1	-0.60	Ambiguous	-0.29	Likely Benign	0.11	Likely Benign	0.378	Likely Benign	-2.99	Deleterious	0.944	Possibly Damaging	0.987	Probably Damaging	3.25	Benign	0.08	Tolerated			0.5198	0.3530	Weaken	1	1	2.6	-16.00
c.395T>G	F132C 2D AIThe SynGAP1 missense variant F132C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from the four high‑accuracy predictors) also indicates likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-10.013	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.331	Likely Benign	-4.55	Deleterious	0.938	Possibly Damaging	0.498	Possibly Damaging	3.29	Benign	0.00	Affected			0.2677	0.0925		-4	-2	-0.3	-44.04
c.623C>T	P208L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P208L has no ClinVar entry and is present in gnomAD (ID 6‑33435265‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, while those that agree on a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions that are inconclusive are Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125								6-33435265-C-T	1	6.20e-7	-10.013	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	2.35	Destabilizing	0.5	0.04	Likely Benign	1.20	Ambiguous	0.67	Ambiguous	0.466	Likely Benign	-8.49	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	0.01	Affected	3.44	12	0.2219	0.6191		-3	-3	5.4	16.04
c.618C>G	I206M 2D AIThe SynGAP1 I206M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, and FATHMM, whereas tools that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With six pathogenic predictions versus four benign and three uncertain, the overall evidence leans toward pathogenicity. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-10.008	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	0.42	Likely Benign	0.6	1.21	Ambiguous	0.82	Ambiguous	1.08	Destabilizing	0.085	Likely Benign	-2.42	Neutral	0.838	Possibly Damaging	0.467	Possibly Damaging	3.64	Benign	0.01	Affected			0.0576	0.2716		2	1	-2.6	18.03
c.154T>C	S52P 2D AIThe SynGAP1 missense variant S52P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict a pathogenic outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes); and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for S52P. This conclusion does not contradict ClinVar, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.291804	Structured	0.457753	Uncertain	0.499	0.677	0.000											-10.007	Likely Pathogenic	0.797	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-1.28	Neutral	0.676	Possibly Damaging	0.693	Possibly Damaging	4.07	Benign	0.00	Affected			0.2276	0.5909		1	-1	-0.8	10.04
c.1792C>G	L598V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L598V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as inconclusive. Overall, the majority of evidence points to a pathogenic impact, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000					Uncertain		1				-10.002	Likely Pathogenic	0.578	Likely Pathogenic	Likely Benign	1.89	Ambiguous	0.1	1.58	Ambiguous	1.74	Ambiguous	1.01	Destabilizing	0.221	Likely Benign	-2.92	Deleterious	0.944	Possibly Damaging	0.786	Possibly Damaging	3.21	Benign	0.02	Affected	3.37	35	0.1082	0.1795		2	1	0.4	-14.03	218.4	29.6	0.0	0.0	0.8	0.0						X		Potentially Benign	The iso-butyl side chain of Leu598, located on an α helix (res. Glu582-Met603), packs hydrophobically with other hydrophobic residues in the inter-helix space (e.g., Ile602, Phe594, Ile510).In the variant simulations, Val598, which has similar size and physicochemical properties to leucine, resides in the inter-helix hydrophobic space in a similar manner to Leu598 in the WT. This causes no negative effects on the protein structure.
c.2060G>A	R687Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687Q is annotated in ClinVar as benign (ClinVar ID 2693600.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, SGM‑Consensus indicating pathogenicity, and Foldetta (integrating FoldX‑MD and Rosetta outputs) classifying it as benign. With three high‑accuracy tools giving benign or uncertain results and only one (SGM‑Consensus) suggesting pathogenicity, the overall evidence leans toward a benign effect. This prediction aligns with the ClinVar benign classification, indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000					Likely Benign		1				-10.002	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.92	Ambiguous	0.1	-0.37	Likely Benign	0.28	Likely Benign	1.55	Destabilizing	0.401	Likely Benign	-3.37	Deleterious	1.000	Probably Damaging	0.844	Possibly Damaging	3.91	Benign	0.03	Affected	3.42	17	0.2143	0.1952		1	1	1.0	-28.06
c.145T>C	C49R 2D AIThe SynGAP1 missense variant C49R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain and no Foldetta (FoldX‑MD/Rosetta) result is available. Taken together, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-10.000	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.320	Likely Benign	-3.53	Deleterious	0.676	Possibly Damaging	0.761	Possibly Damaging	3.95	Benign	0.00	Affected			0.1605	0.2120		-4	-3	-7.0	53.05
c.1525G>T	A509S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, polyPhen‑2 HumDiv, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Four tools give uncertain or inconclusive results (FoldX, Rosetta, Foldetta, premPS). High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus inconclusive, and Foldetta is also inconclusive. Overall, the majority of standard predictors lean toward pathogenicity, while the most reliable single‑tool prediction (AlphaMissense‑Optimized) suggests benign. Given the balance of evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-9.997	Likely Pathogenic	0.171	Likely Benign	Likely Benign	0.83	Ambiguous	0.1	1.63	Ambiguous	1.23	Ambiguous	0.59	Ambiguous	0.621	Likely Pathogenic	-2.18	Neutral	0.119	Benign	0.468	Possibly Damaging	-1.35	Pathogenic	0.01	Affected			0.2410	0.4384		1	1	-2.6	16.00
c.632G>A	S211N 2D AIThe SynGAP1 S211N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and premPS. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the overall prediction leans toward pathogenicity, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-9.995	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	0.60	Ambiguous	1.2	1.39	Ambiguous	1.00	Ambiguous	1.21	Destabilizing	0.174	Likely Benign	-2.22	Neutral	0.982	Probably Damaging	0.747	Possibly Damaging	3.95	Benign	0.09	Tolerated			0.1534	0.4863		1	1	-2.7	27.03
c.688T>A	C230S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are REVEL, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. With an equal split of 7 benign versus 7 pathogenic predictions overall, the higher‑confidence tools lean toward pathogenicity. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-9.994	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.05	Likely Benign	0.24	Likely Benign	1.08	Destabilizing	0.859	Likely Pathogenic	-8.24	Deleterious	0.421	Benign	0.115	Benign	5.91	Benign	0.07	Tolerated			0.4926	0.1822		0	-1	-3.3	-16.06
c.689G>C	C230S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C230S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign calls come from FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM; pathogenic calls come from REVEL, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. No prediction or stability result is missing. Overall, the predictions are evenly split between benign and pathogenic, leaving the variant’s functional impact uncertain. This uncertainty does not contradict ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-9.994	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.05	Likely Benign	0.24	Likely Benign	1.08	Destabilizing	0.844	Likely Pathogenic	-8.24	Deleterious	0.421	Benign	0.115	Benign	5.91	Benign	0.07	Tolerated			0.4926	0.1822		0	-1	-3.3	-16.06
c.1043T>C	V348A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further highlight the discrepancy: AlphaMissense‑Optimized predicts a benign effect, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as pathogenic. Taken together, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict ClinVar status, which currently has no entry for V348A. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-9.993	Likely Pathogenic	0.767	Likely Pathogenic	Likely Benign	2.46	Destabilizing	0.1	3.13	Destabilizing	2.80	Destabilizing	2.23	Destabilizing	0.175	Likely Benign	-3.42	Deleterious	0.622	Possibly Damaging	0.152	Benign	1.59	Pathogenic	0.14	Tolerated			0.3223	0.2437		0	0	-2.4	-28.05
c.1529T>C	I510T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Foldetta—classify the variant as pathogenic, while Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-9.993	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	3.08	Destabilizing	0.2	1.99	Ambiguous	2.54	Destabilizing	1.95	Destabilizing	0.914	Likely Pathogenic	-3.63	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.43	Pathogenic	0.00	Affected			0.0960	0.0440		0	-1	-5.2	-12.05
c.1897C>G	L633V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633V is not reported in ClinVar and is present in the gnomAD database (ID 6‑33440949‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, SGM‑Consensus, and Foldetta; the Rosetta score is uncertain and therefore not considered. High‑accuracy methods give a pathogenic consensus: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenic. Overall, the majority of evidence supports a pathogenic impact for L633V, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000								6-33440949-C-G	1	6.20e-7	-9.992	Likely Pathogenic	0.760	Likely Pathogenic	Likely Benign	2.32	Destabilizing	0.2	1.71	Ambiguous	2.02	Destabilizing	1.32	Destabilizing	0.327	Likely Benign	-2.99	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.86	Benign	0.03	Affected	3.37	34	0.1517	0.2766		1	2	0.4	-14.03
c.167T>C	L56P 2D AIThe SynGAP1 missense variant L56P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-9.991	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic										0.307	Likely Benign	-2.62	Deleterious	0.943	Possibly Damaging	0.944	Probably Damaging	3.77	Benign	0.00	Affected			0.3806	0.1342		-3	-3	-5.4	-16.04
c.3365G>A	G1122D 2D AIThe SynGAP1 missense variant G1122D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors benign (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that G1122D is most likely benign, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.896620	Disordered	0.814918	Binding	0.357	0.932	0.875											-9.991	Likely Pathogenic	0.430	Ambiguous	Likely Benign										0.332	Likely Benign	-0.49	Neutral	0.411	Benign	0.091	Benign	4.49	Benign	0.10	Tolerated			0.1746	0.2035		1	-1	-3.1	58.04
c.2047A>C	I683L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b. Remaining methods (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the balance of evidence favors a benign impact for I683L, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-9.988	Likely Pathogenic	0.488	Ambiguous	Likely Benign	0.63	Ambiguous	0.1	0.76	Ambiguous	0.70	Ambiguous	0.69	Ambiguous	0.286	Likely Benign	-2.00	Neutral	0.011	Benign	0.056	Benign	3.43	Benign	0.04	Affected			0.0957	0.3185		2	2	-0.7	0.00
c.587T>C	L196S 2D AIThe SynGAP1 missense variant L196S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is Likely Pathogenic, while Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-9.987	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.353	Likely Benign	-4.75	Deleterious	0.437	Benign	0.186	Benign	3.65	Benign	0.00	Affected			0.3473	0.0736		-3	-2	-4.6	-26.08
c.856C>G	L286V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L286V is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—consistently predict a pathogenic impact; AlphaMissense‑Default and Rosetta are uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized indicates benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.122885	Structured	0.385647	Uncertain	0.932	0.260	0.000											-9.986	Likely Pathogenic	0.500	Ambiguous	Likely Benign	2.44	Destabilizing	0.5	1.63	Ambiguous	2.04	Destabilizing	1.26	Destabilizing	0.676	Likely Pathogenic	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.71	Pathogenic	0.01	Affected			0.1492	0.3007		2	1	0.4	-14.03
c.1343C>G	A448G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A448G resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas those that predict pathogenicity are Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; FoldX is inconclusive. High‑accuracy assessments further clarify the impact: AlphaMissense‑Optimized reports a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.292774	Uncertain	0.973	0.257	0.000											-9.984	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign	1.76	Ambiguous	0.0	2.45	Destabilizing	2.11	Destabilizing	1.00	Destabilizing	0.378	Likely Benign	-3.95	Deleterious	0.998	Probably Damaging	0.980	Probably Damaging	3.15	Benign	0.06	Tolerated			0.2135	0.2936		1	0	-2.2	-14.03
c.2023A>T	N675Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-9.981	Likely Pathogenic	0.553	Ambiguous	Likely Benign	3.02	Destabilizing	1.3	-0.81	Ambiguous	1.11	Ambiguous	0.19	Likely Benign	0.439	Likely Benign	-5.86	Deleterious	1.000	Probably Damaging	0.955	Probably Damaging	3.38	Benign	0.01	Affected			0.0603	0.6417		-2	-2	2.2	49.07
c.1385A>G	K462R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462R is catalogued in gnomAD (ID 6‑33438290‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Three tools (Rosetta, Foldetta, premPS) yield uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta is uncertain, so neither provides decisive evidence. Overall, the majority of reliable predictors lean toward a benign effect. This consensus does not contradict ClinVar status, which is currently absent. Thus, based on available predictions, K462R is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125								6-33438290-A-G	1	6.20e-7	-9.980	Likely Pathogenic	0.184	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.90	Ambiguous	0.52	Ambiguous	0.84	Ambiguous	0.246	Likely Benign	-2.75	Deleterious	0.983	Probably Damaging	0.962	Probably Damaging	3.43	Benign	0.09	Tolerated	3.37	34	0.4995	0.1201		2	3	-0.6	28.01
c.2057G>C	G686A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy methods give a pathogenic verdict from AlphaMissense‑Optimized and a Likely Pathogenic consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), while Foldetta predicts benign stability. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-9.975	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	-0.39	Likely Benign	0.2	-0.46	Likely Benign	-0.43	Likely Benign	0.58	Ambiguous	0.321	Likely Benign	-5.19	Deleterious	0.993	Probably Damaging	0.732	Possibly Damaging	3.37	Benign	0.13	Tolerated			0.3744	0.4131		1	0	2.2	14.03
c.3166G>T	G1056C 2D AIThe SynGAP1 missense variant G1056C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988291	Disordered	0.868632	Binding	0.402	0.935	0.875											-9.974	Likely Pathogenic	0.122	Likely Benign	Likely Benign										0.432	Likely Benign	-0.70	Neutral	0.994	Probably Damaging	0.777	Possibly Damaging	1.83	Pathogenic	0.06	Tolerated			0.1414	0.4439		-3	-3	2.9	46.09
c.838T>C	Y280H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280H is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Among the available in‑silico predictors, none indicate a benign effect; all 14 tools that produced a classification predict pathogenicity: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive or missing. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125											-9.970	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.01	Destabilizing	0.3	2.58	Destabilizing	2.80	Destabilizing	1.95	Destabilizing	0.588	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.94	Pathogenic	0.01	Affected			0.2021	0.0212		0	2	-1.9	-26.03
c.1382C>T	A461V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Because the majority of standard predictors (nine benign vs. three pathogenic) favor a benign outcome, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-9.968	Likely Pathogenic	0.436	Ambiguous	Likely Benign	-0.08	Likely Benign	0.3	0.34	Likely Benign	0.13	Likely Benign	0.02	Likely Benign	0.141	Likely Benign	-3.05	Deleterious	0.983	Probably Damaging	0.273	Benign	3.43	Benign	0.66	Tolerated			0.0819	0.5078		0	0	2.4	28.05
c.1534G>C	E512Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512Q missense change is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Because the variant is absent from ClinVar and gnomAD, there is no external evidence to contradict the computational predictions. Overall, the balance of high‑confidence tools leans toward a pathogenic interpretation, though the presence of an equal number of benign predictions indicates that the evidence remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-9.964	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	0.09	Likely Benign	0.1	0.42	Likely Benign	0.26	Likely Benign	0.00	Likely Benign	0.283	Likely Benign	-2.86	Deleterious	0.947	Possibly Damaging	0.706	Possibly Damaging	3.32	Benign	0.14	Tolerated			0.1523	0.4815		2	2	0.0	-0.98
c.1576G>A	V526I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V526I variant is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID: 6‑33438819‑G‑A). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of tools (seven benign vs. five pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for V526I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000								6-33438819-G-A			-9.962	Likely Pathogenic	0.526	Ambiguous	Likely Benign	0.07	Likely Benign	0.3	0.41	Likely Benign	0.24	Likely Benign	0.02	Likely Benign	0.540	Likely Pathogenic	-0.99	Neutral	0.929	Possibly Damaging	0.917	Probably Damaging	-1.34	Pathogenic	0.15	Tolerated	3.37	35	0.0630	0.3307		3	4	0.3	14.03
c.3625C>G	L1209V 2D AIThe SynGAP1 L1209V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Taken together, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-9.962	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.152	Likely Benign	-2.39	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1383	0.2289		2	1	0.4	-14.03
c.1495A>G	R499G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R499G is listed in gnomAD (variant ID 6‑33438527‑A‑G) but has no ClinVar entry. Prediction tools that assess the variant’s effect on protein function overwhelmingly indicate a deleterious outcome: REVEL, FoldX‑MD (Rosetta component), Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as pathogenic. Only FoldX (overall) and AlphaMissense‑Optimized report uncertain results, which are treated as unavailable evidence. No tool predicts a benign effect. High‑accuracy assessments specifically show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as pathogenic. Taken together, the preponderance of evidence supports a pathogenic classification for R499G, and this conclusion is not contradicted by any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.071867	Structured	0.386723	Uncertain	0.899	0.146	0.000								6-33438527-A-G	3	1.86e-6	-9.960	Likely Pathogenic	0.789	Likely Pathogenic	Ambiguous	1.55	Ambiguous	0.1	2.75	Destabilizing	2.15	Destabilizing	1.41	Destabilizing	0.681	Likely Pathogenic	-4.50	Deleterious	0.958	Probably Damaging	0.769	Possibly Damaging	-1.47	Pathogenic	0.01	Affected	3.37	35	0.2888	0.1798		-2	-3	4.1	-99.14
c.958G>T	V320F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V320F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on benign impact include REVEL, premPS, and SIFT, whereas tools that agree on pathogenic impact include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as inconclusive. Because the majority of available predictions and the SGM‑Consensus favor pathogenicity, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for V320F. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.419626	Uncertain	0.905	0.266	0.125											-9.958	Likely Pathogenic	0.877	Likely Pathogenic	Ambiguous	1.49	Ambiguous	1.4	1.55	Ambiguous	1.52	Ambiguous	0.44	Likely Benign	0.237	Likely Benign	-3.26	Deleterious	0.994	Probably Damaging	0.944	Probably Damaging	1.79	Pathogenic	0.06	Tolerated			0.0473	0.3064		-1	-1	-1.4	48.04
c.2195G>T	R732M 2D AIThe SynGAP1 missense variant R732M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and ESM1b. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta results are unavailable. Overall, the balance of evidence (5 benign vs 3 pathogenic predictions) indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.846163	Disordered	0.412403	Uncertain	0.427	0.673	0.750											-9.956	Likely Pathogenic	0.414	Ambiguous	Likely Benign										0.098	Likely Benign	-1.42	Neutral	0.840	Possibly Damaging	0.357	Benign	2.55	Benign	0.01	Affected			0.1432	0.2980		0	-1	6.4	-24.99
c.1757A>C	D586A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D586A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include FoldX, SIFT, and premPS, whereas a majority of predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains inconclusive. No evidence from the uncertain tools (Rosetta, Foldetta) alters this consensus. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-9.955	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.41	Likely Benign	0.2	0.88	Ambiguous	0.65	Ambiguous	0.25	Likely Benign	0.693	Likely Pathogenic	-4.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.22	Pathogenic	0.31	Tolerated			0.3397	0.4673		0	-2	5.3	-44.01
c.1217A>G	Y406C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome, and the Foldetta stability assessment (combining FoldX‑MD and Rosetta) predicts a destabilizing, pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while both SGM‑Consensus and Foldetta are pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for Y406C, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-9.954	Likely Pathogenic	0.810	Likely Pathogenic	Ambiguous	2.47	Destabilizing	0.2	3.22	Destabilizing	2.85	Destabilizing	1.27	Destabilizing	0.229	Likely Benign	-6.72	Deleterious	0.998	Probably Damaging	0.851	Possibly Damaging	3.78	Benign	0.01	Affected			0.3026	0.2861		0	-2	3.8	-60.04
c.2105A>T	Q702L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the balance of evidence leans toward a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-9.954	Likely Pathogenic	0.149	Likely Benign	Likely Benign	-0.13	Likely Benign	0.0	0.09	Likely Benign	-0.02	Likely Benign	0.16	Likely Benign	0.392	Likely Benign	-5.66	Deleterious	0.939	Possibly Damaging	0.838	Possibly Damaging	3.42	Benign	0.00	Affected			0.0584	0.3628		-2	-2	7.3	-14.97
c.952C>T	P318S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318S is present in gnomAD (variant ID 6‑33437857‑C‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a deleterious effect. Pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Taken together, the overwhelming majority of evidence supports a pathogenic classification, and this conclusion is consistent with the absence of a ClinVar record rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000								6-33437857-C-T	1	6.19e-7	-9.954	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	2.22	Destabilizing	0.1	1.71	Ambiguous	1.97	Ambiguous	1.00	Destabilizing	0.626	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.87	Pathogenic	0.03	Affected	3.38	23	0.3692	0.5653		-1	1	0.8	-10.04
c.485G>T	R162L 2D AIThe SynGAP1 missense variant R162L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, giving six concordant benign calls. Two tools predict a pathogenic effect: ESM1b and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250											-9.952	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-1.83	Neutral	0.001	Benign	0.003	Benign	4.05	Benign	0.15	Tolerated			0.1888	0.5894		-3	-2	8.3	-43.03
c.1498C>A	L500M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L500M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The premPS score is uncertain. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive because it yields a 2‑to‑2 split. No other high‑accuracy predictions are available. Overall, the majority of high‑accuracy tools lean toward a benign interpretation, and this assessment does not contradict the lack of ClinVar reporting. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000											-9.945	Likely Pathogenic	0.301	Likely Benign	Likely Benign	0.15	Likely Benign	0.0	-0.09	Likely Benign	0.03	Likely Benign	0.92	Ambiguous	0.590	Likely Pathogenic	-1.99	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	-1.36	Pathogenic	0.01	Affected			0.0710	0.2202		4	2	-1.9	18.03
c.1009A>C	K337Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K337Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-9.944	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.00	Likely Benign	0.0	0.88	Ambiguous	0.44	Likely Benign	0.43	Likely Benign	0.305	Likely Benign	-3.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.70	Pathogenic	0.01	Affected			0.3672	0.1219		1	1	0.4	-0.04
c.835C>G	R279G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R279G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote) which labels it “Likely Pathogenic.” AlphaMissense‑Optimized is uncertain, providing no definitive evidence. High‑accuracy assessments further support pathogenicity: the SGM‑Consensus remains “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125											-9.941	Likely Pathogenic	0.920	Likely Pathogenic	Ambiguous	3.10	Destabilizing	0.7	2.85	Destabilizing	2.98	Destabilizing	1.11	Destabilizing	0.442	Likely Benign	-5.37	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.92	Pathogenic	0.02	Affected			0.2961	0.2209		-3	-2	4.1	-99.14
c.883A>C	T295P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T295P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX and AlphaMissense‑Optimized, whereas the remaining evaluated algorithms (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. High‑accuracy assessments further show that AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as likely pathogenic, and Foldetta reports an uncertain stability change. With the majority of evidence pointing to deleterious effects, the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125											-9.941	Likely Pathogenic	0.688	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	3.30	Destabilizing	1.78	Ambiguous	0.60	Ambiguous	0.531	Likely Pathogenic	-4.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.90	Pathogenic	0.02	Affected			0.2442	0.5327		0	-1	-0.9	-3.99
c.1983G>C	Q661H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q661H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-9.938	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.1	0.07	Likely Benign	0.43	Likely Benign	0.09	Likely Benign	0.282	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.42	Benign	0.02	Affected			0.1276	0.3424		3	0	0.3	9.01
c.1983G>T	Q661H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q661H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-9.938	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.1	0.07	Likely Benign	0.43	Likely Benign	0.09	Likely Benign	0.282	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.42	Benign	0.02	Affected			0.1276	0.3424		3	0	0.3	9.01
c.1651C>A	L551M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551M is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438894‑C‑A). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, while those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools report an uncertain outcome: premPS and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of predictions lean toward a benign effect, and this does not contradict the ClinVar “Uncertain” classification. Thus, the variant is most likely benign based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000					Uncertain		1	6-33438894-C-A	7	4.34e-6	-9.937	Likely Pathogenic	0.480	Ambiguous	Likely Benign	-0.07	Likely Benign	0.1	0.13	Likely Benign	0.03	Likely Benign	0.71	Ambiguous	0.544	Likely Pathogenic	-0.56	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	-1.48	Pathogenic	0.06	Tolerated	3.37	35	0.0838	0.2701		4	2	-1.9	18.03	246.5	-18.6	0.0	0.0	0.3	0.0						X		Potentially Benign	L551 is located on an α-helix (res. Ala533-Val560). The iso-butyl side chain of Leu551 hydrophobically packs with nearby hydrophobic residues such as Cys547, Phe652, Leu633, and Ile630 in the inter-helix space. In the variant simulations, the thioether side chain of Met551 can maintain similar hydrophobic interactions as Leu551 in the WT, thus causing no negative effect on the protein structure during the simulations.
c.853T>G	C285G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a pathogenic interpretation: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict deleterious effects. Tools that assess protein stability (FoldX, Rosetta, Foldetta) and AlphaMissense‑Optimized return uncertain results, providing no clear evidence for or against pathogenicity. High‑accuracy assessments further support a likely pathogenic verdict: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the consensus of the majority of predictors indicates that the variant is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.937	Likely Pathogenic	0.859	Likely Pathogenic	Ambiguous	1.26	Ambiguous	0.0	1.57	Ambiguous	1.42	Ambiguous	1.50	Destabilizing	0.564	Likely Pathogenic	-9.86	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.78	Pathogenic	0.04	Affected			0.3509	0.2922		-3	-3	-2.9	-46.09
c.1316T>C	L439P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-9.929	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	6.30	Destabilizing	0.2	7.62	Destabilizing	6.96	Destabilizing	1.28	Destabilizing	0.539	Likely Pathogenic	-5.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.21	Benign	0.02	Affected			0.3426	0.1192		-3	-3	-5.4	-16.04
c.2146C>G	R716G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R716G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Other stability predictors (FoldX, Rosetta, premPS) are also Uncertain. Overall, the balance of evidence from the majority of tools and the SGM‑Consensus indicates a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000											-9.927	Likely Pathogenic	0.728	Likely Pathogenic	Likely Benign	1.32	Ambiguous	0.1	1.63	Ambiguous	1.48	Ambiguous	0.72	Ambiguous	0.359	Likely Benign	-5.70	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.36	Benign	0.01	Affected			0.3437	0.2466		-3	-2	4.1	-99.14
c.3806T>G	V1269G 2D AIThe SynGAP1 missense variant V1269G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus is pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-9.927	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.420	Likely Benign	-5.91	Deleterious	0.995	Probably Damaging	0.999	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2180	0.2557		-1	-3	-4.6	-42.08
c.161A>T	N54I 2D AIThe SynGAP1 missense variant N54I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000											-9.919	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.201	Likely Benign	-1.70	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.15	Benign	0.00	Affected			0.0637	0.6793		-2	-3	8.0	-0.94
c.1625A>C	N542T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542T is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are SIFT and Rosetta. Tools that predict a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-9.918	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	1.13	Ambiguous	0.1	0.20	Likely Benign	0.67	Ambiguous	0.75	Ambiguous	0.784	Likely Pathogenic	-5.37	Deleterious	0.997	Probably Damaging	0.990	Probably Damaging	-1.41	Pathogenic	0.12	Tolerated			0.1120	0.5872		0	0	2.8	-13.00
c.2533G>T	D845Y 2D AIThe SynGAP1 missense variant D845Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that D845Y is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-9.917	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.384	Likely Benign	-6.55	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0590	0.6699		-4	-3	2.2	48.09
c.2137C>A	P713T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further clarify the picture: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, whereas AlphaMissense‑Optimized and Foldetta provide inconclusive results and are treated as unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for P713T, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-9.915	Likely Pathogenic	0.819	Likely Pathogenic	Ambiguous	1.15	Ambiguous	0.0	0.46	Likely Benign	0.81	Ambiguous	0.65	Ambiguous	0.225	Likely Benign	-6.72	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.34	Benign	0.00	Affected			0.1417	0.3818		0	-1	0.9	3.99
c.1502T>G	I501S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized; all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign change, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both predict pathogenicity. Overall, the preponderance of evidence points to a pathogenic effect for I501S. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-9.914	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	3.23	Destabilizing	0.2	2.40	Destabilizing	2.82	Destabilizing	1.79	Destabilizing	0.511	Likely Pathogenic	-5.14	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.04	Affected			0.2370	0.0858		-1	-2	-5.3	-26.08
c.2041G>A	G681S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, while those that predict a pathogenic outcome are SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain result. Overall, the majority of tools lean toward pathogenicity, but the presence of a benign prediction from AlphaMissense‑Optimized and an uncertain Foldetta score leaves the assessment inconclusive. No ClinVar entry exists, so there is no contradiction with clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-9.913	Likely Pathogenic	0.716	Likely Pathogenic	Likely Benign	2.11	Destabilizing	1.3	-0.23	Likely Benign	0.94	Ambiguous	0.41	Likely Benign	0.483	Likely Benign	-5.99	Deleterious	0.997	Probably Damaging	0.780	Possibly Damaging	3.45	Benign	0.08	Tolerated			0.2591	0.4584		1	0	-0.4	30.03
c.3761A>T	E1254V 2D AIThe SynGAP1 missense variant E1254V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by the majority of in silico methods. High‑accuracy assessments further reinforce a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-9.913	Likely Pathogenic	0.814	Likely Pathogenic	Ambiguous										0.350	Likely Benign	-5.15	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.0481	0.5894		-2	-2	7.7	-29.98
c.640C>G	L214V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L214V is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The remaining methods—FoldX, Rosetta, premPS, and AlphaMissense‑Optimized—yield uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-9.913	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	1.80	Ambiguous	0.4	0.54	Ambiguous	1.17	Ambiguous	0.89	Ambiguous	0.495	Likely Benign	-2.54	Deleterious	0.384	Benign	0.070	Benign	5.78	Benign	0.01	Affected			0.1469	0.3887		2	1	0.4	-14.03
c.1522G>A	D508N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508N missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, FATHMM, AlphaMissense‑Optimized) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b). Three tools remain uncertain (Rosetta, Foldetta, AlphaMissense‑Default). High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized classifies the change as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—returns a pathogenic verdict; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an inconclusive result. Because the consensus of the high‑accuracy methods is split, the overall prediction is ambiguous, but the balance of evidence leans toward pathogenicity. This assessment does not contradict ClinVar, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-9.909	Likely Pathogenic	0.411	Ambiguous	Likely Benign	0.11	Likely Benign	0.1	1.24	Ambiguous	0.68	Ambiguous	-0.12	Likely Benign	0.265	Likely Benign	-4.62	Deleterious	0.870	Possibly Damaging	0.615	Possibly Damaging	3.32	Benign	0.04	Affected			0.1577	0.4599		2	1	0.0	-0.98
c.1945A>G	M649V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M649V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. With 8 pathogenic versus 3 benign predictions, the overall evidence favors a deleterious effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-9.907	Likely Pathogenic	0.887	Likely Pathogenic	Ambiguous	2.84	Destabilizing	0.3	2.55	Destabilizing	2.70	Destabilizing	1.05	Destabilizing	0.370	Likely Benign	-3.99	Deleterious	0.997	Probably Damaging	0.735	Possibly Damaging	3.40	Benign	0.06	Tolerated			0.2389	0.3121		2	1	2.3	-32.06
c.1718G>A	R573Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R573Q is reported in ClinVar as Pathogenic (ClinVar ID 1176819.0) and is not present in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default, while only SIFT predicts a benign outcome. Two tools give inconclusive results: Rosetta (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.032433	Uncertain	0.934	0.235	0.000					Likely Pathogenic		1				-9.900	Likely Pathogenic	0.923	Likely Pathogenic	Ambiguous	2.28	Destabilizing	0.8	1.94	Ambiguous	2.11	Destabilizing	1.08	Destabilizing	0.733	Likely Pathogenic	-3.16	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	-1.31	Pathogenic	0.12	Tolerated	3.37	35	0.2390	0.1651		1	1	1.0	-28.06	230.1	49.9	0.0	0.0	-0.6	0.0	X	X						Potentially Pathogenic	The guanidinium group of Arg573, located in an α-helix (res. Arg563-Glu578), forms a salt bridge with the carboxylate groups of Glu582 and/or Asp586 from a nearby α-helix (res. Glu582-Met603) in the WT simulations. Additionally, the Arg573 side chain stacks planarly with the aromatic phenol ring of Tyr665 and hydrogen bonds with the hydroxyl group of Ser668 from another α-helix (res. Ser641-Ser668). In the variant simulations, although the carboxamide group of the Gln573 side chain can hydrogen bond with the carboxylate group of Glu582 or the hydroxyl group of Ser668, these interactions are not as coordinated, stable, or strong as those of the positively charged Arg573. Consequently, the integrity of the opposing α-helix end (res. Glu582-Met603) is weakened. Overall, the residue swap has the potential to substantially affect the tertiary structure assembly during the protein folding process.
c.3823C>T	R1275W 2D AIThe SynGAP1 missense variant R1275W is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33447871‑C‑T). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a split vote (2 pathogenic, 1 benign, 1 uncertain). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the balance of evidence leans toward a pathogenic classification, and this assessment does not contradict ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.790317	Binding	0.723	0.697	0.500								6-33447871-C-T	3	1.93e-6	-9.895	Likely Pathogenic	0.513	Ambiguous	Likely Benign										0.161	Likely Benign	-4.76	Deleterious	0.999	Probably Damaging	0.875	Possibly Damaging	2.51	Benign	0.00	Affected	3.77	5	0.1269	0.2372		-3	2	3.6	30.03
c.631A>G	S211G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, and ESM1b; Rosetta is uncertain. High‑accuracy methods give a benign result for AlphaMissense‑Optimized and for Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs two pathogenic). No evidence from ClinVar contradicts these predictions. Overall, the balance of evidence—including the unanimous benign calls from the high‑accuracy tools—suggests that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-9.895	Likely Pathogenic	0.265	Likely Benign	Likely Benign	0.30	Likely Benign	0.2	0.54	Ambiguous	0.42	Likely Benign	1.07	Destabilizing	0.067	Likely Benign	-3.17	Deleterious	0.787	Possibly Damaging	0.404	Benign	3.92	Benign	0.07	Tolerated			0.2560	0.4337		1	0	0.4	-30.03
c.3772C>G	Q1258E 2D AIThe SynGAP1 missense variant Q1258E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-9.894	Likely Pathogenic	0.666	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-2.39	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.01	Pathogenic	0.00	Affected			0.0958	0.1897		2	2	0.0	0.98
c.1393C>G	L465V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default—indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports likely pathogenic; and Foldetta, which combines FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar uncertain status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000					Uncertain		1				-9.893	Likely Pathogenic	0.838	Likely Pathogenic	Ambiguous	2.46	Destabilizing	0.1	2.66	Destabilizing	2.56	Destabilizing	1.21	Destabilizing	0.276	Likely Benign	-2.98	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.44	Pathogenic	0.10	Tolerated	3.37	34	0.1493	0.3378		2	1	0.4	-14.03	204.3	30.9	0.0	0.0	-0.4	0.6						X		Potentially Benign	The iso-butyl side chain of Leu465, located in the middle of an α helix (res. Ala461–Phe476), packs with hydrophobic residues (e.g., Phe464, Met468, Tyr497, Ile494) in an inter-helix space formed with two other α helices (res. Ala461–Phe476 and res. Thr488-Gly502). In the variant simulations, the iso-propyl side chain of Val465 is equally sized and similarly hydrophobic as the original side chain of Leu465. Hence, the mutation does not exert any negative effects on the protein structure based on the variant simulations.