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.2122C>T	L708F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L708F is not reported in ClinVar and is present in gnomAD (ID 6‑33441587‑C‑T). Functional prediction tools that reach consensus classify the change as benign: REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions are limited to polyPhen‑2 HumDiv and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) return uncertain or no result. High‑accuracy assessments give AlphaMissense‑Optimized a benign score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta indicates no significant destabilization (uncertain). Overall, the preponderance of evidence supports a benign effect for L708F, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000								6-33441587-C-T	2	1.24e-6	-9.154	Likely Pathogenic	0.436	Ambiguous	Likely Benign	1.48	Ambiguous	0.3	0.93	Ambiguous	1.21	Ambiguous	0.37	Likely Benign	0.110	Likely Benign	-2.46	Neutral	0.931	Possibly Damaging	0.326	Benign	3.29	Benign	0.07	Tolerated	3.50	9	0.0497	0.2366		0	2	-1.0	34.02
c.2137C>T	P713S 2D AIThe SynGAP1 missense variant P713S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, Rosetta, 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 results are provided by FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this ambiguity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates a likely pathogenic effect, and Foldetta likewise yields an uncertain stability change. Overall, the majority of tools lean toward a pathogenic interpretation, and this aligns 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	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-8.496	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous	0.91	Ambiguous	0.7	0.19	Likely Benign	0.55	Ambiguous	0.62	Ambiguous	0.261	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.00	Affected			0.3234	0.3674		1	-1	0.8	-10.04
c.2138C>G	P713R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools, premPS and AlphaMissense‑Optimized, are inconclusive. 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, while the most accurate methods give conflicting results. Thus, the variant is most likely pathogenic based on the current evidence, and this assessment does not contradict ClinVar status, which has no 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											-12.101	Likely Pathogenic	0.930	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.21	Likely Benign	0.25	Likely Benign	0.86	Ambiguous	0.331	Likely Benign	-7.42	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.00	Affected			0.1366	0.2335		0	-2	-2.9	59.07
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.3901C>T	P1301S 2D AIThe SynGAP1 missense variant P1301S is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign effect, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875											-4.537	Likely Benign	0.071	Likely Benign	Likely Benign										0.087	Likely Benign	1.84	Neutral	0.000	Benign	0.001	Benign	3.29	Benign	0.95	Tolerated			0.2799	0.3436		1	-1	0.8	-10.04
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.3992T>A	I1331N 2D AIThe SynGAP1 missense variant I1331N is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451866‑T‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated tools predict a pathogenic impact, and there is no conflict with ClinVar status. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875								6-33451866-T-A			-3.788	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.237	Likely Benign	-4.09	Deleterious	0.984	Probably Damaging	0.979	Probably Damaging	3.29	Benign	0.00	Affected	3.77	5	0.1012	0.0666		-3	-2	-8.0	0.94
c.1231A>T	I411F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411F 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 limited to FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain. High‑accuracy methods reinforce this view: 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. No prediction is missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, 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	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-13.377	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	5.71	Destabilizing	0.1	4.53	Destabilizing	5.12	Destabilizing	0.73	Ambiguous	0.503	Likely Pathogenic	-3.69	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.30	Benign	0.00	Affected			0.0538	0.2853		1	0	-1.7	34.02
c.1232T>G	I411S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411S 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 methods 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 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	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-13.763	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.59	Destabilizing	0.2	3.83	Destabilizing	3.71	Destabilizing	1.91	Destabilizing	0.603	Likely Pathogenic	-5.50	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.30	Benign	0.00	Affected			0.2262	0.1487		-1	-2	-5.3	-26.08
c.1276A>T	N426Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two main groups: benign predictions come from REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b. Two tools remain uncertain: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on the current predictive landscape. 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											-8.510	Likely Pathogenic	0.541	Ambiguous	Likely Benign	0.47	Likely Benign	0.0	-0.50	Ambiguous	-0.02	Likely Benign	0.23	Likely Benign	0.341	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.30	Benign	0.25	Tolerated			0.0578	0.3338		-2	-2	2.2	49.07
c.1338G>C	E446D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a damaging effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Taken together, the majority of evidence points to 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 Benign	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-5.668	Likely Benign	0.562	Ambiguous	Likely Benign	1.65	Ambiguous	0.7	0.80	Ambiguous	1.23	Ambiguous	0.68	Ambiguous	0.171	Likely Benign	-2.40	Neutral	0.986	Probably Damaging	0.960	Probably Damaging	3.30	Benign	0.18	Tolerated			0.1657	0.4275		3	2	0.0	-14.03
c.1338G>T	E446D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E446D lies in the GAP domain. ClinVar has no entry for this variant and it is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools report a pathogenic signal: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The remaining predictors (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Taken together, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this is consistent with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-5.668	Likely Benign	0.562	Ambiguous	Likely Benign	1.65	Ambiguous	0.7	0.80	Ambiguous	1.23	Ambiguous	0.68	Ambiguous	0.171	Likely Benign	-2.40	Neutral	0.986	Probably Damaging	0.960	Probably Damaging	3.30	Benign	0.18	Tolerated			0.1657	0.4275		3	2	0.0	-14.03
c.1340T>A	V447D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V447D lies in the GAP domain. ClinVar has no entry for this change, and it is absent from gnomAD. Prediction tools that agree on benign impact are REVEL and FATHMM, whereas the remaining predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classify the variant as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta also reports a pathogenic effect. Overall, the evidence points to a pathogenic effect for V447D, 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	0.283801	Uncertain	0.970	0.243	0.000											-16.643	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.34	Destabilizing	0.1	3.59	Destabilizing	3.97	Destabilizing	2.29	Destabilizing	0.491	Likely Benign	-5.33	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.30	Benign	0.01	Affected			0.1424	0.0541		-2	-3	-7.7	15.96
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.1369A>T	S457C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S457C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, FoldX, Foldetta, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give mixed results: AlphaMissense‑Optimized is inconclusive and therefore not used as evidence; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign effect. Overall, the majority of individual predictors lean toward pathogenicity, while the high‑accuracy Foldetta result suggests benign stability. Given the predominance of pathogenic calls and the lack of ClinVar evidence, 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	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-8.152	Likely Pathogenic	0.815	Likely Pathogenic	Ambiguous	-0.12	Likely Benign	0.0	-0.79	Ambiguous	-0.46	Likely Benign	0.56	Ambiguous	0.497	Likely Benign	-4.81	Deleterious	0.999	Probably Damaging	0.987	Probably Damaging	3.30	Benign	0.01	Affected			0.0865	0.6284		0	-1	3.3	16.06
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.1523A>G	D508G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. FoldX‑MD is inconclusive and is treated as unavailable. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM Consensus, and a pathogenic prediction from Foldetta. Overall, the majority of evidence, including the high‑accuracy tools, supports a pathogenic effect. This conclusion does not contradict ClinVar, 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	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-8.478	Likely Pathogenic	0.622	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.2	3.20	Destabilizing	2.04	Destabilizing	0.13	Likely Benign	0.368	Likely Benign	-6.61	Deleterious	0.997	Probably Damaging	0.933	Probably Damaging	3.30	Benign	0.07	Tolerated			0.3821	0.4528		1	-1	3.1	-58.04
c.1535A>G	E512G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E512G 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, premPS, 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. The remaining tools—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive 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, and PROVEAN), and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E512G, 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	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-11.996	Likely Pathogenic	0.817	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.1	1.84	Ambiguous	1.35	Ambiguous	0.17	Likely Benign	0.381	Likely Benign	-6.46	Deleterious	0.997	Probably Damaging	0.915	Probably Damaging	3.30	Benign	0.02	Affected			0.3262	0.4185		0	-2	3.1	-72.06
c.1561G>C	E521Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521Q 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, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. 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 predicts a benign stability change. Overall, the majority of evidence (9 benign vs. 4 pathogenic predictions) supports 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.		GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-8.310	Likely Pathogenic	0.777	Likely Pathogenic	Likely Benign	-0.28	Likely Benign	0.2	0.19	Likely Benign	-0.05	Likely Benign	-0.06	Likely Benign	0.262	Likely Benign	-2.15	Neutral	0.992	Probably Damaging	0.993	Probably Damaging	3.30	Benign	0.11	Tolerated			0.1580	0.6552		2	2	0.0	-0.98
c.1613A>T	E538V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E538V missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, Rosetta, Foldetta, premPS, and FATHMM. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX give uncertain results and are treated as unavailable. 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 evidence points to a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for it. 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											-11.537	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.67	Ambiguous	0.0	-0.49	Likely Benign	0.09	Likely Benign	0.23	Likely Benign	0.310	Likely Benign	-5.53	Deleterious	0.929	Possibly Damaging	0.641	Possibly Damaging	3.30	Benign	0.04	Affected			0.0722	0.4436		-2	-2	7.7	-29.98
c.175C>A	L59M 2D AIThe SynGAP1 missense variant L59M 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, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evaluated predictors lean toward a benign interpretation. Consequently, the variant is most likely benign based on current computational 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 Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-3.394	Likely Benign	0.618	Likely Pathogenic	Likely Benign										0.088	Likely Benign	-0.65	Neutral	0.824	Possibly Damaging	0.910	Probably Damaging	3.30	Benign	0.00	Affected			0.0772	0.3311		4	2	-1.9	18.03
c.1846G>C	D616H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616H 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, premPS, and FATHMM. Those that agree on a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results—Rosetta and AlphaMissense‑Optimized—so their outputs are treated as unavailable for inference. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is Pathogenic. Overall, the majority of evidence points to a pathogenic effect. The variant’s predicted pathogenicity 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	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-9.815	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	2.13	Destabilizing	0.2	1.89	Ambiguous	2.01	Destabilizing	0.45	Likely Benign	0.316	Likely Benign	-5.57	Deleterious	0.999	Probably Damaging	0.952	Probably Damaging	3.30	Benign	0.03	Affected			0.1330	0.4273		1	-1	0.3	22.05
c.2011G>C	D671H 2D 3DClick to see structure in 3D Viewer AISynGAP1 D671H is not reported in ClinVar and is absent from gnomAD. Benign predictions are provided by REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy tools give mixed results: AlphaMissense‑Optimized is uncertain, SGM Consensus predicts pathogenic, and Foldetta predicts benign. Overall, the balance of evidence leans toward pathogenicity, 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	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-11.501	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.0	0.29	Likely Benign	0.39	Likely Benign	0.09	Likely Benign	0.300	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.939	Probably Damaging	3.30	Benign	0.01	Affected			0.1627	0.6509		1	-1	0.3	22.05
c.2029A>G	S677G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677G 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, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. Predictions that are inconclusive—FoldX, Rosetta, Foldetta, and premPS—are treated as unavailable. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the evidence supports a benign classification for S677G, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-5.126	Likely Benign	0.060	Likely Benign	Likely Benign	0.98	Ambiguous	0.1	1.20	Ambiguous	1.09	Ambiguous	0.64	Ambiguous	0.126	Likely Benign	-1.38	Neutral	0.002	Benign	0.001	Benign	3.30	Benign	0.26	Tolerated			0.2885	0.5325		1	0	0.4	-30.03
c.2049C>G	I683M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I683M variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive 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 definitive predictions (five pathogenic vs. three benign) point to a pathogenic impact. Thus, 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.		GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-9.010	Likely Pathogenic	0.424	Ambiguous	Likely Benign	0.69	Ambiguous	0.1	0.68	Ambiguous	0.69	Ambiguous	0.74	Ambiguous	0.296	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.986	Probably Damaging	3.30	Benign	0.01	Affected			0.0933	0.2662		2	1	-2.6	18.03
c.2099T>C	L700P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while only FATHMM predicts it benign. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus 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 overwhelming consensus of pathogenic predictions, 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	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-13.092	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	7.29	Destabilizing	0.5	12.85	Destabilizing	10.07	Destabilizing	1.84	Destabilizing	0.541	Likely Pathogenic	-4.31	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	3.30	Benign	0.01	Affected			0.3603	0.1025		-3	-3	-5.4	-16.04
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.3164G>C	G1055A 2D AIThe SynGAP1 missense variant G1055A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports Likely Benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign 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 Benign		0.982235	Disordered	0.872113	Binding	0.379	0.935	0.875											-6.835	Likely Benign	0.083	Likely Benign	Likely Benign										0.244	Likely Benign	0.15	Neutral	0.649	Possibly Damaging	0.148	Benign	3.30	Benign	1.00	Tolerated			0.3350	0.5144		1	0	2.2	14.03
c.3992T>G	I1331S 2D AIThe SynGAP1 I1331S 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, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic. 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.			0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-3.014	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.230	Likely Benign	-3.40	Deleterious	0.984	Probably Damaging	0.969	Probably Damaging	3.30	Benign	0.00	Affected			0.2929	0.0836		-1	-2	-5.3	-26.08
c.4008G>C	E1336D 2D AIThe SynGAP1 missense variant E1336D is listed in ClinVar (ID 3323942.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a benign classification. 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, consistent with the ClinVar benign designation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750					Likely Benign		1				-3.344	Likely Benign	0.596	Likely Pathogenic	Likely Benign										0.062	Likely Benign	-1.92	Neutral	0.001	Benign	0.003	Benign	3.30	Benign	0.00	Affected	3.77	5	0.1995	0.5101		2	3	0.0	-14.03
c.4008G>T	E1336D 2D AIThe SynGAP1 missense variant E1336D is catalogued in gnomAD (ID 6‑33451882‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. Only two tools—SIFT and AlphaMissense‑Default—predict pathogenicity. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also reports it as likely benign. 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 benign classification, 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 Benign		0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750								6-33451882-G-T			-3.344	Likely Benign	0.596	Likely Pathogenic	Likely Benign										0.065	Likely Benign	-1.92	Neutral	0.001	Benign	0.003	Benign	3.30	Benign	0.00	Affected	3.77	5	0.1995	0.5101		2	3	0.0	-14.03
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.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.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.1265A>C	E422A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422A missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the balance of evidence (seven pathogenic versus six benign predictions) points to a likely pathogenic effect for E422A, and this conclusion is not contradicted by the absence of a ClinVar annotation. 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											-12.088	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.0	0.25	Likely Benign	0.37	Likely Benign	0.26	Likely Benign	0.371	Likely Benign	-5.43	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.31	Benign	0.01	Affected			0.2949	0.4459		0	-1	5.3	-58.04
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.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.1340T>G	V447G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V447G 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 and FATHMM, while the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that V447G is most likely pathogenic, and this conclusion does not contradict 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.		GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000											-13.648	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	3.81	Destabilizing	0.1	4.62	Destabilizing	4.22	Destabilizing	2.28	Destabilizing	0.499	Likely Benign	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.31	Benign	0.01	Affected			0.1863	0.2240		-1	-3	-4.6	-42.08
c.1388A>T	D463V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D463V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, premPS, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Rosetta, Foldetta, and AlphaMissense‑Optimized. 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. Overall, the majority of evidence points toward a pathogenic impact for D463V, 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	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-12.374	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	0.98	Ambiguous	0.61	Ambiguous	0.33	Likely Benign	0.521	Likely Pathogenic	-7.95	Deleterious	0.973	Probably Damaging	0.658	Possibly Damaging	3.31	Benign	0.09	Tolerated			0.0713	0.5526		-2	-3	7.7	-15.96
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.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.1557A>C	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519D 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, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven benign predictions versus six pathogenic ones, the overall evidence slightly favors a benign classification. This conclusion does not contradict the ClinVar status, which contains no pathogenic assertion for this variant. 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											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.183	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1557A>T	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E519D 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, SIFT, and FATHMM, while those that predict a pathogenic outcome 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 (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign interpretation. This consensus 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.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.182	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1562A>G	E521G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E521G 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it is a 2‑vs‑2 split and is treated as unavailable. Overall, the majority of evidence points to a benign impact. The variant is most likely benign 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.		GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-6.636	Likely Benign	0.767	Likely Pathogenic	Likely Benign	0.18	Likely Benign	0.1	0.58	Ambiguous	0.38	Likely Benign	0.14	Likely Benign	0.289	Likely Benign	-3.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2932	0.5455		0	-2	3.1	-72.06
c.1744G>A	E582K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E582K 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, FoldX, Rosetta, premPS, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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) is inconclusive, and Foldetta predicts a benign effect on protein stability. Taken together, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-11.826	Likely Pathogenic	0.814	Likely Pathogenic	Ambiguous	0.20	Likely Benign	0.1	0.07	Likely Benign	0.14	Likely Benign	0.02	Likely Benign	0.168	Likely Benign	-1.83	Neutral	0.994	Probably Damaging	0.994	Probably Damaging	3.31	Benign	0.33	Tolerated			0.2038	0.3762		0	1	-0.4	-0.94
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.1817G>T	S606I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606I 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, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain. 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 evidence points toward a pathogenic impact for S606I. 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 Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-14.552	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	-0.60	Ambiguous	0.1	-0.08	Likely Benign	-0.34	Likely Benign	0.41	Likely Benign	0.288	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.31	Benign	0.01	Affected			0.0891	0.4162		-1	-2	5.3	26.08
c.1952A>G	E651G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E651G 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 PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Predictions that are uncertain or unavailable are FoldX, Rosetta, ESM1b, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as unavailable. Overall, the majority of tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this does not contradict the lack of ClinVar annotation. 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	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-7.596	In-Between	0.591	Likely Pathogenic	Likely Benign	0.66	Ambiguous	0.1	1.61	Ambiguous	1.14	Ambiguous	0.32	Likely Benign	0.444	Likely Benign	-4.78	Deleterious	0.999	Probably Damaging	0.935	Probably Damaging	3.31	Benign	0.06	Tolerated			0.2908	0.4488		0	-2	3.1	-72.06
c.1961A>T	E654V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E654V 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, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the majority of tools (8 pathogenic vs. 4 benign) and the SGM‑Consensus result support a pathogenic classification. 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	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-12.306	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	-0.33	Likely Benign	0.11	Likely Benign	0.21	Likely Benign	0.540	Likely Pathogenic	-6.66	Deleterious	0.988	Probably Damaging	0.734	Possibly Damaging	3.31	Benign	0.01	Affected			0.0686	0.4757		-2	-2	7.7	-29.98
c.2012A>T	D671V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671V missense variant 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, premPS, and FATHMM. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the majority of predictions (seven pathogenic vs. three benign) support a pathogenic classification. There is no ClinVar entry to contradict this assessment, so 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	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-12.376	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.1	0.51	Ambiguous	0.57	Ambiguous	0.14	Likely Benign	0.379	Likely Benign	-6.08	Deleterious	0.975	Probably Damaging	0.885	Possibly Damaging	3.31	Benign	0.01	Affected			0.0820	0.6651		-2	-3	7.7	-15.96
c.2029A>C	S677R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677R 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. Those that predict a pathogenic effect are FoldX, ESM1b, and AlphaMissense‑Default. Uncertain results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, 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 tools and the high‑accuracy benign prediction suggest 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	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-9.388	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	2.59	Destabilizing	0.1	0.73	Ambiguous	1.66	Ambiguous	0.71	Ambiguous	0.104	Likely Benign	-2.49	Neutral	0.385	Benign	0.037	Benign	3.31	Benign	0.12	Tolerated			0.1120	0.4195		0	-1	-3.7	69.11
c.2031T>A	S677R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677R 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. Those that predict a pathogenic effect are FoldX, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and premPS. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta is uncertain. Overall, the majority of consensus tools (six benign vs. three pathogenic) lean toward a benign interpretation. This prediction does not contradict any ClinVar status, as none is available. 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.		GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-9.388	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	2.59	Destabilizing	0.1	0.73	Ambiguous	1.66	Ambiguous	0.71	Ambiguous	0.150	Likely Benign	-2.49	Neutral	0.385	Benign	0.037	Benign	3.31	Benign	0.12	Tolerated			0.1120	0.4195		0	-1	-3.7	69.11
c.2031T>G	S677R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677R 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. Those that predict a pathogenic effect are FoldX, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and premPS. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta is uncertain. Overall, the majority of consensus tools (six benign vs. three pathogenic) lean toward a benign interpretation. This prediction does not contradict any ClinVar status, as none is available. 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.		GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-9.388	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	2.59	Destabilizing	0.1	0.73	Ambiguous	1.66	Ambiguous	0.71	Ambiguous	0.150	Likely Benign	-2.49	Neutral	0.385	Benign	0.037	Benign	3.31	Benign	0.12	Tolerated			0.1120	0.4195		0	-1	-3.7	69.11
c.2056G>T	G686C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, FATHMM, and the protein‑folding stability method Foldetta; pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, with the SGM‑Consensus score labeling the variant as 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. 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	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-12.790	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.2	0.41	Likely Benign	0.33	Likely Benign	0.93	Ambiguous	0.553	Likely Pathogenic	-8.14	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	3.31	Benign	0.02	Affected			0.1209	0.3246		-3	-3	2.9	46.09
c.2057G>T	G686V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686V has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on benign impact are Rosetta and FATHMM, while the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) indicate a pathogenic effect. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for G686V, 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	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-13.751	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.89	Ambiguous	0.5	0.21	Likely Benign	0.55	Ambiguous	0.74	Ambiguous	0.570	Likely Pathogenic	-8.08	Deleterious	1.000	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.01	Affected			0.1059	0.3646		-1	-3	4.6	42.08
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.2132T>A	L711Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L711Q 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. Tools that predict a pathogenic effect include FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM Consensus, and Foldetta; Rosetta is uncertain. High‑accuracy methods give a consistent pathogenic signal: 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) predicts Pathogenic. No predictions are missing or inconclusive. Based on the preponderance 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	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000											-11.792	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	2.93	Destabilizing	0.0	1.68	Ambiguous	2.31	Destabilizing	1.63	Destabilizing	0.388	Likely Benign	-5.67	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.31	Benign	0.00	Affected			0.1041	0.0488		-2	-2	-7.3	14.97
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.2854G>A	G952S 2D AIThe SynGAP1 missense variant G952S is listed in ClinVar (ID 1325573.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443406‑G‑A). All evaluated in‑silico predictors agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports a benign classification, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.910621	Binding	0.341	0.926	0.750					Conflicting		2	6-33443406-G-A	2	1.24e-6	-6.190	Likely Benign	0.077	Likely Benign	Likely Benign										0.167	Likely Benign	0.19	Neutral	0.000	Benign	0.002	Benign	3.31	Benign	0.07	Tolerated	3.77	5	0.2509	0.5502		1	0	-0.4	30.03
c.3163G>A	G1055R 2D AIThe SynGAP1 missense variant G1055R 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, 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) also favors benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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.			0.982235	Disordered	0.872113	Binding	0.379	0.935	0.875											-8.778	Likely Pathogenic	0.375	Ambiguous	Likely Benign										0.275	Likely Benign	-0.09	Neutral	0.970	Probably Damaging	0.728	Possibly Damaging	3.31	Benign	0.08	Tolerated			0.1013	0.4733		-3	-2	-4.1	99.14
c.3163G>C	G1055R 2D AIThe SynGAP1 missense variant G1055R 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, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign outcome (2 benign vs. 1 pathogenic, 1 uncertain). 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, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.982235	Disordered	0.872113	Binding	0.379	0.935	0.875											-8.778	Likely Pathogenic	0.375	Ambiguous	Likely Benign										0.275	Likely Benign	-0.09	Neutral	0.970	Probably Damaging	0.728	Possibly Damaging	3.31	Benign	0.08	Tolerated			0.1013	0.4733		-3	-2	-4.1	99.14
c.395T>C	F132S 2D AIThe SynGAP1 missense variant F132S 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, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, 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) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence (five pathogenic vs four benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-4.177	Likely Benign	0.996	Likely Pathogenic	Likely Pathogenic										0.329	Likely Benign	-4.54	Deleterious	0.567	Possibly Damaging	0.249	Benign	3.31	Benign	0.00	Affected			0.4869	0.0000		-3	-2	-3.6	-60.10
c.3991A>T	I1331F 2D AIThe SynGAP1 missense variant I1331F 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, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-4.220	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.46	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	3.31	Benign	0.00	Affected			0.0522	0.3225		1	0	-1.7	34.02
c.1238C>G	P413R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P413R 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 remaining tools—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The remaining methods, Foldetta and Rosetta, yield uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect, 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	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-15.523	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.40	Destabilizing	0.2	1.34	Ambiguous	1.87	Ambiguous	1.07	Destabilizing	0.562	Likely Pathogenic	-8.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.32	Benign	0.01	Affected			0.1550	0.2199		0	-2	-2.9	59.07
c.1253A>T	K418I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418I 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, premPS, and FATHMM. In contrast, the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain results. 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 K418I, 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	0.360134	Uncertain	0.948	0.263	0.000											-14.895	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.51	Ambiguous	0.0	0.64	Ambiguous	0.58	Ambiguous	0.27	Likely Benign	0.428	Likely Benign	-7.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.32	Benign	0.01	Affected			0.1297	0.2432		-2	-3	8.4	-15.01
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.1345A>T	S449C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449C is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, FoldX, Rosetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Based on the unanimous benign predictions and lack of ClinVar evidence, 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 Benign	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000											-2.207	Likely Benign	0.050	Likely Benign	Likely Benign	0.48	Likely Benign	0.0	-0.31	Likely Benign	0.09	Likely Benign	-0.57	Ambiguous	0.067	Likely Benign	0.48	Neutral	0.000	Benign	0.000	Benign	3.32	Benign	0.21	Tolerated			0.0864	0.5012		0	-1	3.3	16.06
c.1381G>C	A461P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and FATHMM, whereas the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS remains uncertain. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is pathogenic. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, 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	GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-13.869	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	-0.35	Likely Benign	0.1	5.09	Destabilizing	2.37	Destabilizing	0.84	Ambiguous	0.451	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.849	Possibly Damaging	3.32	Benign	0.03	Affected			0.1748	0.3949		1	-1	-3.4	26.04
c.1382C>A	A461D 2D AIThe SynGAP1 missense variant A461D 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. The majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta are inconclusive, providing no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that A461D 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	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-14.918	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.89	Ambiguous	1.1	2.18	Destabilizing	1.54	Ambiguous	1.09	Destabilizing	0.477	Likely Benign	-5.47	Deleterious	0.997	Probably Damaging	0.792	Possibly Damaging	3.32	Benign	0.01	Affected			0.1533	0.2016		0	-2	-5.3	44.01
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.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.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.1534G>A	E512K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512K 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 REVEL, FoldX, SIFT, FATHMM, premPS, and Foldetta, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is 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 benign. Overall, seven tools predict pathogenicity versus six predicting benignity, with one uncertain result. Thus, the variant is most likely pathogenic based on the current computational evidence, 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	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-13.927	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.1	0.63	Ambiguous	0.40	Likely Benign	-0.03	Likely Benign	0.344	Likely Benign	-3.85	Deleterious	0.962	Probably Damaging	0.658	Possibly Damaging	3.32	Benign	0.06	Tolerated			0.2844	0.4776		0	1	-0.4	-0.94
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.1600T>A	S534T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Thus, the overall evidence strongly supports a benign classification, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-4.925	Likely Benign	0.104	Likely Benign	Likely Benign	0.10	Likely Benign	0.1	0.46	Likely Benign	0.28	Likely Benign	0.19	Likely Benign	0.200	Likely Benign	-2.42	Neutral	0.676	Possibly Damaging	0.933	Probably Damaging	3.32	Benign	0.07	Tolerated			0.1238	0.5064		1	1	0.1	14.03
c.1600T>C	S534P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438843‑T‑C). Functional prediction tools that report a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy assessments are consistent with a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the aggregate predictions, the variant is most likely benign, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000					Uncertain		1	6-33438843-T-C	3	1.86e-6	-5.056	Likely Benign	0.265	Likely Benign	Likely Benign	-0.40	Likely Benign	0.2	0.35	Likely Benign	-0.03	Likely Benign	0.47	Likely Benign	0.203	Likely Benign	-3.81	Deleterious	0.993	Probably Damaging	0.993	Probably Damaging	3.32	Benign	0.05	Affected	3.37	35	0.2071	0.4650		-1	1	-0.8	10.04
c.1643A>G	E548G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT and FATHMM, while the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; SGM‑Consensus also classifies the variant as likely pathogenic. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, SGM‑Consensus confirming a likely pathogenic status, and Foldetta yielding an inconclusive stability change. Overall, the consensus of the available predictions points to a pathogenic effect for E548G, 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	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-12.010	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.97	Ambiguous	0.1	1.66	Ambiguous	1.32	Ambiguous	0.59	Ambiguous	0.521	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.32	Benign	0.06	Tolerated			0.2638	0.3654		0	-2	3.1	-72.06
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.1848T>A	D616E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616E missense variant is catalogued in gnomAD (ID 6‑33440900‑T‑A) but has no ClinVar submission. Functional prediction tools show a split assessment: benign calls come from REVEL, both polyPhen‑2 HumDiv and HumVar, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from PROVEAN, SIFT, and AlphaMissense‑Default. The remaining predictors (FoldX, Rosetta, Foldetta, premPS, ESM1b) are inconclusive. A high‑accuracy consensus (SGM) that aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic verdict. AlphaMissense‑Optimized remains benign, and Foldetta, which evaluates protein‑folding stability, is uncertain. Overall, the majority of evidence leans toward pathogenicity, and this conclusion does not conflict with ClinVar because no ClinVar classification 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								6-33440900-T-A	1	6.20e-7	-7.250	In-Between	0.695	Likely Pathogenic	Likely Benign	0.96	Ambiguous	0.1	1.52	Ambiguous	1.24	Ambiguous	0.58	Ambiguous	0.092	Likely Benign	-2.85	Deleterious	0.421	Benign	0.232	Benign	3.32	Benign	0.03	Affected	3.37	35	0.1225	0.4128		2	3	0.0	14.03
c.1848T>G	D616E 2D 3DClick to see structure in 3D Viewer AISynGAP1 D616E is not reported in ClinVar but is present in gnomAD (ID 6‑33440900‑T‑G). Functional prediction tools that agree on benign impact include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, SIFT, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) 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 uncertain. Overall, the majority of conventional predictors lean toward a benign effect, but the high‑accuracy consensus is split, leaving the variant’s clinical significance unresolved. Thus, the variant is most likely benign based on the bulk of predictions, and this does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000								6-33440900-T-G	3	1.86e-6	-7.250	In-Between	0.695	Likely Pathogenic	Likely Benign	0.96	Ambiguous	0.1	1.52	Ambiguous	1.24	Ambiguous	0.58	Ambiguous	0.092	Likely Benign	-2.85	Deleterious	0.421	Benign	0.232	Benign	3.32	Benign	0.03	Affected	3.37	35	0.1225	0.4128		2	3	0.0	14.03
c.2018T>A	L673Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673Q 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 Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX and Foldetta, as well as AlphaMissense‑Default, are inconclusive and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta remains uncertain. Overall, the majority of available predictions (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion 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.		GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-11.963	Likely Pathogenic	0.445	Ambiguous	Likely Benign	1.56	Ambiguous	0.2	2.32	Destabilizing	1.94	Ambiguous	1.02	Destabilizing	0.190	Likely Benign	-3.40	Deleterious	1.000	Probably Damaging	0.968	Probably Damaging	3.32	Benign	0.03	Affected			0.1045	0.1172		-2	-2	-7.3	14.97
c.2030G>C	S677T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM all classify it as benign. No tool predicts pathogenicity. The only inconclusive results come from Rosetta (Uncertain) and Foldetta (Uncertain), which are treated as unavailable evidence. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta remains Uncertain. Overall, the consensus of available predictions indicates that S677T is most likely benign, 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 Benign	GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-4.760	Likely Benign	0.063	Likely Benign	Likely Benign	-0.17	Likely Benign	0.3	-0.85	Ambiguous	-0.51	Ambiguous	0.15	Likely Benign	0.070	Likely Benign	-0.97	Neutral	0.008	Benign	0.007	Benign	3.32	Benign	0.30	Tolerated			0.1775	0.6985		1	1	0.1	14.03
c.2044T>C	Y682H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y682H is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the majority of other in silico predictors (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict it to be pathogenic. The high‑accuracy consensus method SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized and the protein‑folding stability predictor Foldetta both return uncertain results, and FoldX and Rosetta individually are inconclusive. Overall, the preponderance of pathogenic predictions outweighs the benign ones, indicating that Y682H is most likely pathogenic. This assessment 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.	Likely Pathogenic	GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-9.255	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	1.78	Ambiguous	0.0	0.56	Ambiguous	1.17	Ambiguous	1.23	Destabilizing	0.399	Likely Benign	-4.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.32	Benign	0.03	Affected			0.2405	0.0868		0	2	-1.9	-26.03
c.2044T>G	Y682D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. The high‑accuracy methods reinforce this view: 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 reports a pathogenic effect. With no ClinVar assertion to oppose these findings, the variant is most likely pathogenic. 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											-15.094	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	2.81	Destabilizing	0.4	3.06	Destabilizing	2.94	Destabilizing	0.96	Ambiguous	0.639	Likely Pathogenic	-9.60	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.32	Benign	0.01	Affected			0.4191	0.0760		-4	-3	-2.2	-48.09
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.2146C>T	R716W 2D 3DClick to see structure in 3D Viewer AIClinVar has no entry for this SynGAP1 R716W variant, and it is present in the gnomAD database (ID 6‑33441611‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, premPS, and Foldetta, while those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic. With two high‑accuracy tools supporting benign and one supporting pathogenic, the overall prediction leans toward a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for the 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								6-33441611-C-T	5	3.10e-6	-11.543	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	-0.11	Likely Benign	0.0	0.87	Ambiguous	0.38	Likely Benign	0.31	Likely Benign	0.339	Likely Benign	-6.72	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.32	Benign	0.00	Affected	3.50	9	0.1303	0.3252		-3	2	3.6	30.03
c.3992T>C	I1331T 2D AIThe SynGAP1 missense variant I1331T 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, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, 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 (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence (seven pathogenic vs. three 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.			0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-2.953	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-2.69	Deleterious	0.947	Possibly Damaging	0.950	Probably Damaging	3.32	Benign	0.00	Affected			0.1115	0.1550		0	-1	-5.2	-12.05
c.3993T>G	I1331M 2D AIThe SynGAP1 I1331M missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Considering the majority of consensus‑based and individual predictors, the variant is most likely benign. 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 Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-4.202	Likely Benign	0.883	Likely Pathogenic	Ambiguous										0.143	Likely Benign	-1.69	Neutral	0.984	Probably Damaging	0.979	Probably Damaging	3.32	Benign	0.00	Affected			0.0698	0.3220		2	1	-2.6	18.03
c.1257G>C	E419D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419D 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, PROVEAN, SIFT, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or inconclusive predictions come from Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain (unavailable). Overall, the majority of evidence points to a benign 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.		GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-7.036	In-Between	0.869	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.1	0.87	Ambiguous	0.52	Ambiguous	0.48	Likely Benign	0.170	Likely Benign	-2.40	Neutral	0.995	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.10	Tolerated			0.1966	0.4906		3	2	0.0	-14.03
c.1257G>T	E419D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419D 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, PROVEAN, SIFT, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or inconclusive predictions come from Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain (unavailable). Overall, the majority of evidence points to a benign 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.		GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-7.036	In-Between	0.869	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.1	0.87	Ambiguous	0.52	Ambiguous	0.48	Likely Benign	0.170	Likely Benign	-2.40	Neutral	0.995	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.10	Tolerated			0.1966	0.4906		3	2	0.0	-14.03
c.1271T>A	V424D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V424D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy tools reinforce this view: 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 pathogenicity. No prediction is missing or inconclusive. Consequently, 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	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-15.531	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.60	Destabilizing	0.1	3.50	Destabilizing	3.55	Destabilizing	2.13	Destabilizing	0.615	Likely Pathogenic	-5.87	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	3.33	Benign	0.00	Affected			0.1536	0.0845		-2	-3	-7.7	15.96
c.1360A>T	I454F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I454F 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. All other evaluated algorithms—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy assessments 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. premPS is uncertain and does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the absence of benign evidence, the variant is most likely pathogenic, with no ClinVar status to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.312811	Uncertain	0.965	0.182	0.000											-12.468	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	4.15	Destabilizing	0.7	2.96	Destabilizing	3.56	Destabilizing	0.70	Ambiguous	0.464	Likely Benign	-3.95	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.33	Benign	0.00	Affected			0.0422	0.2560		1	0	-1.7	34.02
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.1388A>C	D463A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely pathogenic, and Foldetta predicts a benign effect on protein stability. Overall, the majority of tools and the consensus high‑accuracy prediction lean toward pathogenicity, 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	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-8.607	Likely Pathogenic	0.894	Likely Pathogenic	Ambiguous	-0.04	Likely Benign	0.1	0.96	Ambiguous	0.46	Likely Benign	0.43	Likely Benign	0.425	Likely Benign	-6.96	Deleterious	0.978	Probably Damaging	0.602	Possibly Damaging	3.33	Benign	0.29	Tolerated			0.3591	0.5169		0	-2	5.3	-44.01
c.1556A>C	E519A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519A missense variant is listed in ClinVar as Pathogenic (ClinVar ID 1029087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Uncertain predictions from Rosetta and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy results are: AlphaMissense‑Optimized – unavailable; SGM‑Consensus – Pathogenic; Foldetta – Benign. Overall, the predictions are balanced, but the high‑accuracy Foldetta result leans toward benign while the consensus leans toward pathogenic, leaving the assessment inconclusive. Based on the available predictions, the variant is most likely benign, contradicting the ClinVar pathogenic classification. 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					Likely Pathogenic		1				-8.557	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	-0.05	Likely Benign	0.0	0.55	Ambiguous	0.25	Likely Benign	0.00	Likely Benign	0.384	Likely Benign	-5.23	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.33	Benign	0.10	Tolerated	3.37	35	0.3544	0.3545		0	-1	5.3	-58.04	162.4	83.5	-0.1	0.1	-0.2	0.0						X		Potentially Benign	Glu519 is located at the beginning of an α-α loop between the two α-helices (res. Gly502-Tyr518 and Ala533-Val560). In the WT simulations, the carboxylate side chain of Glu519 does not make any specific interactions. Accordingly, the Ala residue swap does not show any negative structural effects in the variant simulations. However, it should be noted that Glu519 faces the missing part of the N-terminal in the model, and thus its potential role in maintaining the tertiary structure might be de-emphasized in the current model.
c.1613A>G	E538G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from 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, is labeled 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. No folding‑stability result is definitive. Overall, the balance of evidence, including the majority‑vote SGM Consensus and the higher number of pathogenic predictions, points to a pathogenic effect for E538G. 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.	Likely Pathogenic	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-9.258	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	0.91	Ambiguous	0.0	1.07	Ambiguous	0.99	Ambiguous	0.31	Likely Benign	0.285	Likely Benign	-5.10	Deleterious	0.993	Probably Damaging	0.700	Possibly Damaging	3.33	Benign	0.03	Affected			0.3173	0.3713		0	-2	3.1	-72.06
c.1642G>A	E548K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548K missense variant 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 impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicting likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicating a benign effect on protein stability. Overall, the balance of evidence leans toward a pathogenic interpretation, with no conflict with 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	GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-13.734	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-0.34	Likely Benign	0.0	-0.19	Likely Benign	-0.27	Likely Benign	0.13	Likely Benign	0.348	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	3.33	Benign	0.09	Tolerated			0.1990	0.4491		0	1	-0.4	-0.94
c.1876A>G	I626V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I626V 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, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are uncertain or unavailable are AlphaMissense‑Default, FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also indicates a likely benign outcome, while Foldetta’s stability analysis is inconclusive. Based on the overall consensus of the available predictions, the variant is most likely benign, 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 Benign	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-6.636	Likely Benign	0.398	Ambiguous	Likely Benign	1.24	Ambiguous	0.0	1.06	Ambiguous	1.15	Ambiguous	0.80	Ambiguous	0.182	Likely Benign	-0.80	Neutral	0.969	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.13	Tolerated			0.1003	0.2891		4	3	-0.3	-14.03
c.1946T>G	M649R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649R 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 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 impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a pathogenic effect. Based on the collective evidence, 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	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-14.827	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	5.02	Destabilizing	0.1	5.97	Destabilizing	5.50	Destabilizing	2.09	Destabilizing	0.595	Likely Pathogenic	-5.98	Deleterious	0.985	Probably Damaging	0.464	Possibly Damaging	3.33	Benign	0.00	Affected			0.1635	0.1228		0	-1	-6.4	24.99
c.1952A>C	E651A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E651A 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. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicting it as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign impact. Overall, the balance of evidence leans toward a benign classification, and this conclusion does not contradict the absence of a ClinVar record. 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											-8.694	Likely Pathogenic	0.610	Likely Pathogenic	Likely Benign	0.38	Likely Benign	0.1	0.52	Ambiguous	0.45	Likely Benign	0.23	Likely Benign	0.396	Likely Benign	-4.54	Deleterious	0.986	Probably Damaging	0.875	Possibly Damaging	3.33	Benign	0.13	Tolerated			0.3926	0.5551		0	-1	5.3	-58.04
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.2041G>T	G681C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681C is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all classify it as pathogenic, while only FATHMM predicts a benign outcome. Uncertain calls come from FoldX, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, Foldetta (combining FoldX‑MD and Rosetta) is pathogenic, and AlphaMissense‑Optimized remains inconclusive. Overall, the evidence strongly favors a pathogenic interpretation, 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	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-12.374	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.89	Ambiguous	1.3	2.63	Destabilizing	2.26	Destabilizing	0.66	Ambiguous	0.554	Likely Pathogenic	-8.98	Deleterious	1.000	Probably Damaging	0.959	Probably Damaging	3.33	Benign	0.00	Affected			0.1194	0.3886		-3	-3	2.9	46.09
c.2042G>T	G681V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681V is not reported in ClinVar and is absent from gnomAD. 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 and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus predicts a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic outcome. No other high‑confidence predictions are available. Taken together, the consensus of pathogenic predictions outweighs the single benign call, indicating that G681V is most likely pathogenic. This assessment 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	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-14.043	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	3.21	Destabilizing	2.0	6.12	Destabilizing	4.67	Destabilizing	0.64	Ambiguous	0.572	Likely Pathogenic	-8.98	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	3.33	Benign	0.01	Affected			0.1350	0.3840		-1	-3	4.6	42.08
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.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.2055G>C	L685F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685F is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, 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 support a deleterious effect: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. FoldX and Rosetta predictions are uncertain and are treated as unavailable. Overall, the preponderance of evidence points to a pathogenic impact for the variant, 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	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-12.304	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.62	Ambiguous	0.2	1.80	Ambiguous	1.71	Ambiguous	0.50	Likely Benign	0.300	Likely Benign	-3.99	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.33	Benign	0.01	Affected			0.0724	0.2367		2	0	-1.0	34.02
c.2055G>T	L685F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685F is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, 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 support a deleterious effect: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. FoldX and Rosetta predictions are uncertain and are treated as unavailable. Overall, the preponderance of evidence points to a pathogenic impact for the variant, 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	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-12.304	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.62	Ambiguous	0.2	1.80	Ambiguous	1.71	Ambiguous	0.50	Likely Benign	0.300	Likely Benign	-3.99	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.33	Benign	0.01	Affected			0.0724	0.2367		2	0	-1.0	34.02
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.2093A>T	E698V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E698V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Tools with inconclusive results are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports an uncertain result. Overall, the majority of evidence points to a pathogenic impact for E698V, 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	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-12.797	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.76	Ambiguous	0.0	0.39	Likely Benign	0.58	Ambiguous	0.26	Likely Benign	0.480	Likely Benign	-6.51	Deleterious	0.992	Probably Damaging	0.967	Probably Damaging	3.33	Benign	0.00	Affected			0.0577	0.4546		-2	-2	7.7	-29.98
c.2113A>G	K705E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K705E 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, PROVEAN, SIFT, AlphaMissense‑Optimized, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. 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‑vs‑2 split, and Foldetta predicts a benign stability change. Overall, the majority of evidence (9 benign vs. 4 pathogenic) supports 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.		GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.371	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.10	Likely Benign	0.0	-0.09	Likely Benign	0.01	Likely Benign	0.47	Likely Benign	0.075	Likely Benign	-1.53	Neutral	0.935	Possibly Damaging	0.537	Possibly Damaging	3.33	Benign	0.14	Tolerated			0.2601	0.0789		0	1	0.4	0.94
c.2114A>G	K705R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K705R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate a benign or likely benign outcome. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Thus, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-4.679	Likely Benign	0.126	Likely Benign	Likely Benign	0.10	Likely Benign	0.0	0.35	Likely Benign	0.23	Likely Benign	0.18	Likely Benign	0.094	Likely Benign	-1.66	Neutral	0.960	Probably Damaging	0.545	Possibly Damaging	3.33	Benign	0.06	Tolerated			0.3456	0.0789		3	2	-0.6	28.01
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.2186A>C	N729T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729T is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID 6‑33441651‑A‑C). Consensus among the majority of in‑silico predictors is benign: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Overall, the evidence strongly supports a benign effect, and this conclusion does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625								6-33441651-A-C	1	6.20e-7	-1.952	Likely Benign	0.103	Likely Benign	Likely Benign	0.52	Ambiguous	0.3	1.73	Ambiguous	1.13	Ambiguous	-0.34	Likely Benign	0.052	Likely Benign	-0.52	Neutral	0.123	Benign	0.042	Benign	3.33	Benign	1.00	Tolerated	3.59	7	0.1201	0.4805		0	0	2.8	-13.00
c.593T>A	L198H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198H 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 pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L198H. 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		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-15.650	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.09	Ambiguous	0.2	1.04	Ambiguous	1.07	Ambiguous	0.74	Ambiguous	0.419	Likely Benign	-5.91	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	3.33	Benign	0.00	Affected			0.1057	0.0519		-2	-3	-7.0	23.98
c.593T>C	L198P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions 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 show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a deleterious effect. Thus, 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		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-12.250	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.3	0.40	Likely Benign	0.98	Ambiguous	0.65	Ambiguous	0.491	Likely Benign	-5.87	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.33	Benign	0.00	Affected			0.3882	0.1582		-3	-3	-5.4	-16.04
c.1271T>G	V424G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V424G 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. All other evaluated algorithms—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 further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic consensus (3 pathogenic vs. 1 benign); and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. No predictions are 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 there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-13.697	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	3.90	Destabilizing	0.1	4.84	Destabilizing	4.37	Destabilizing	2.44	Destabilizing	0.622	Likely Pathogenic	-6.26	Deleterious	0.994	Probably Damaging	1.000	Probably Damaging	3.34	Benign	0.00	Affected			0.1396	0.2029		-1	-3	-4.6	-42.08
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.1334A>C	E445A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E445A 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 FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and premPS are inconclusive. 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. Overall, the majority of predictions lean toward pathogenicity, and the high‑accuracy consensus supports a likely pathogenic classification. Thus, 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	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-12.659	Likely Pathogenic	0.849	Likely Pathogenic	Ambiguous	0.09	Likely Benign	0.0	-0.34	Likely Benign	-0.13	Likely Benign	0.56	Ambiguous	0.476	Likely Benign	-5.73	Deleterious	0.997	Probably Damaging	0.991	Probably Damaging	3.34	Benign	0.01	Affected			0.2846	0.4876		0	-1	5.3	-58.04
c.1334A>T	E445V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E445V 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, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, 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, 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 Benign. Overall, the majority of evidence points toward a pathogenic effect. 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	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-14.830	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	-0.67	Ambiguous	-0.17	Likely Benign	0.32	Likely Benign	0.572	Likely Pathogenic	-6.68	Deleterious	0.992	Probably Damaging	0.967	Probably Damaging	3.34	Benign	0.01	Affected			0.0414	0.5233		-2	-2	7.7	-29.98
c.1367A>C	Q456P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q456P is listed in ClinVar with an uncertain significance (ClinVar ID 2697090.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. High‑accuracy methods specifically report pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, which contradicts the current ClinVar uncertain status. 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					Uncertain		1				-15.250	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.2	8.43	Destabilizing	6.06	Destabilizing	0.82	Ambiguous	0.469	Likely Benign	-5.66	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.34	Benign	0.07	Tolerated	3.37	34	0.2256	0.3631		-1	0	1.9	-31.01
c.1370G>C	S457T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S457T has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX and Rosetta provide uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicting likely pathogenic, and Foldetta predicting benign. Overall, the majority of high‑confidence tools lean toward a benign effect, and there is no conflict with the ClinVar status, which is currently unreported. Thus, the variant is most likely benign based on the available predictions. 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											-8.772	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.82	Ambiguous	0.1	-0.57	Ambiguous	0.13	Likely Benign	0.38	Likely Benign	0.273	Likely Benign	-2.83	Deleterious	0.866	Possibly Damaging	0.780	Possibly Damaging	3.34	Benign	0.09	Tolerated			0.1154	0.6487		1	1	0.1	14.03
c.1370G>T	S457I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S457I lies within the GAP domain. ClinVar has no entry for this change, and it is absent from gnomAD. Prediction tools that report a benign effect include FoldX and FATHMM, whereas the majority of other in silico predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized—classify it as pathogenic. Uncertain results come from Rosetta, Foldetta and premPS. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN) is Likely Pathogenic, and Foldetta remains inconclusive. Based on the preponderance 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	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-13.170	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	-0.26	Likely Benign	0.3	-0.96	Ambiguous	-0.61	Ambiguous	0.65	Ambiguous	0.557	Likely Pathogenic	-5.73	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.34	Benign	0.02	Affected			0.0779	0.6095		-1	-2	5.3	26.08
c.1378A>G	K460E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K460E 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, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), Rosetta, and premPS all indicate pathogenicity, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No prediction or folding‑stability result is missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K460E, 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	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-13.304	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.68	Ambiguous	0.0	2.02	Destabilizing	1.85	Ambiguous	1.05	Destabilizing	0.398	Likely Benign	-3.40	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.34	Benign	0.09	Tolerated			0.3966	0.1022		0	1	0.4	0.94
c.1536A>C	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E512D is not reported in ClinVar or gnomAD. Across a broad panel of in silico predictors, the majority indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Only the ESM1b model assigns a pathogenic label, while Rosetta and Foldetta provide uncertain results. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains inconclusive. Consequently, the variant is most likely benign, 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	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	0.259	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			0.2055	0.3089		3	2	0.0	-14.03
c.1536A>T	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E512D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Across the broad panel of in‑silico predictors, the majority (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as benign, whereas only ESM1b predicts it as pathogenic. The high‑accuracy tools give a consistent benign signal: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the evidence strongly supports a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	0.259	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			0.2055	0.3089		3	2	0.0	-14.03
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.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.1921T>C	S641P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and SIFT. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign impact, 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.		GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000											-6.907	Likely Benign	0.378	Ambiguous	Likely Benign	1.73	Ambiguous	1.3	0.07	Likely Benign	0.90	Ambiguous	0.59	Ambiguous	0.205	Likely Benign	-3.05	Deleterious	0.000	Benign	0.000	Benign	3.34	Benign	0.04	Affected			0.2289	0.5791		1	-1	-0.8	10.04
c.1946T>A	M649K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649K is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Benign calls are limited to polyPhen‑2 (HumVar) and FATHMM. High‑accuracy methods reinforce the pathogenic consensus: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among these tools, 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	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-14.533	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.42	Destabilizing	0.0	6.19	Destabilizing	4.81	Destabilizing	1.79	Destabilizing	0.614	Likely Pathogenic	-5.98	Deleterious	0.968	Probably Damaging	0.382	Benign	3.34	Benign	0.01	Affected			0.1438	0.1079		0	-1	-5.8	-3.02
c.1951G>C	E651Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E651Q 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, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all classifying the change as benign. No tool predicts a pathogenic outcome. The high‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign result. Consequently, the variant is most likely benign based on the available predictions, and this assessment 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	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-6.308	Likely Benign	0.476	Ambiguous	Likely Benign	0.13	Likely Benign	0.1	0.15	Likely Benign	0.14	Likely Benign	-0.13	Likely Benign	0.158	Likely Benign	-1.23	Neutral	0.244	Benign	0.075	Benign	3.34	Benign	0.58	Tolerated			0.1438	0.5893		2	2	0.0	-0.98
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.1979T>A	M660K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are polyPhen‑2 HumVar and FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a pathogenic effect. Based on the overwhelming consensus of pathogenic predictions and the corroborating high‑accuracy tools, 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	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-14.123	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.13	Destabilizing	0.1	4.46	Destabilizing	3.80	Destabilizing	2.36	Destabilizing	0.604	Likely Pathogenic	-5.99	Deleterious	0.862	Possibly Damaging	0.216	Benign	3.34	Benign	0.00	Affected			0.1389	0.0856		0	-1	-5.8	-3.02
c.1979T>G	M660R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates 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 prediction is 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	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-15.985	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.95	Destabilizing	0.2	3.52	Destabilizing	3.24	Destabilizing	1.96	Destabilizing	0.588	Likely Pathogenic	-5.99	Deleterious	0.976	Probably Damaging	0.464	Possibly Damaging	3.34	Benign	0.00	Affected			0.1612	0.0957		0	-1	-6.4	24.99
c.2005A>T	N669Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669Y is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include FoldX, FATHMM, and premPS. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. 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 eight pathogenic predictions versus three benign, the overall evidence points to a pathogenic impact. This conclusion is not contradicted by 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	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-13.548	Likely Pathogenic	0.802	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.4	1.29	Ambiguous	0.87	Ambiguous	0.21	Likely Benign	0.546	Likely Pathogenic	-7.01	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.34	Benign	0.00	Affected			0.0666	0.4151		-2	-2	2.2	49.07
c.2006A>T	N669I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N669I is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include premPS and FATHMM, whereas the remaining ten tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the majority‑vote SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), SGM‑Consensus as likely pathogenic, and Foldetta as uncertain (also treated as unavailable). The overall consensus of the available predictions leans strongly toward pathogenicity, and this conclusion does not conflict with 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	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-13.324	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	0.84	Ambiguous	0.0	1.09	Ambiguous	0.97	Ambiguous	0.31	Likely Benign	0.517	Likely Pathogenic	-8.18	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.34	Benign	0.00	Affected			0.0749	0.4697		-2	-3	8.0	-0.94
c.2012A>C	D671A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671A missense variant is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the 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 uncertain. Overall, the balance of evidence favors a pathogenic interpretation, with seven tools supporting pathogenicity versus four supporting benignity. This conclusion does not conflict with 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	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-11.709	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	0.25	Likely Benign	0.1	0.79	Ambiguous	0.52	Ambiguous	0.10	Likely Benign	0.245	Likely Benign	-5.08	Deleterious	0.980	Probably Damaging	0.804	Possibly Damaging	3.34	Benign	0.03	Affected			0.4056	0.5895		0	-2	5.3	-44.01
c.2030G>T	S677I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, premPS, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenicity is suggested only by PROVEAN and SIFT, while Foldetta and ESM1b give uncertain results. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta remains uncertain. 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.		GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-7.942	In-Between	0.156	Likely Benign	Likely Benign	-0.09	Likely Benign	0.0	-2.25	Stabilizing	-1.17	Ambiguous	-0.01	Likely Benign	0.097	Likely Benign	-2.81	Deleterious	0.002	Benign	0.002	Benign	3.34	Benign	0.05	Affected			0.1040	0.6463		-1	-2	5.3	26.08
c.2044T>A	Y682N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y682N 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, while the majority of tools (SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact; FoldX and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as pathogenic. Overall, the evidence strongly favors 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	GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-11.734	Likely Pathogenic	0.859	Likely Pathogenic	Ambiguous	1.86	Ambiguous	0.1	2.22	Destabilizing	2.04	Destabilizing	1.54	Destabilizing	0.564	Likely Pathogenic	-8.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.34	Benign	0.02	Affected			0.2354	0.0928		-2	-2	-2.2	-49.07
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.2122C>A	L708I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708I is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the substitution as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign based on current 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 Benign	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-4.406	Likely Benign	0.116	Likely Benign	Likely Benign	0.42	Likely Benign	0.0	-0.21	Likely Benign	0.11	Likely Benign	-0.05	Likely Benign	0.108	Likely Benign	0.02	Neutral	0.022	Benign	0.021	Benign	3.34	Benign	0.20	Tolerated			0.0749	0.2729		2	2	0.7	0.00
c.2131C>A	L711M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L711M 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. 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‑vs‑2 split, and Foldetta reports an uncertain stability change, which is treated as unavailable evidence. Overall, the majority of individual predictors (six pathogenic vs. five benign) and the available high‑accuracy results lean toward a pathogenic interpretation. Thus, 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	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000											-9.368	Likely Pathogenic	0.679	Likely Pathogenic	Likely Benign	0.39	Likely Benign	0.0	1.11	Ambiguous	0.75	Ambiguous	1.40	Destabilizing	0.216	Likely Benign	-1.86	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.34	Benign	0.00	Affected			0.0755	0.2758		4	2	-1.9	18.03
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.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.2137C>G	P713A 2D 3DClick to see structure in 3D Viewer AISynGAP1 P713A is not reported in ClinVar and is absent from gnomAD. Benign predictions are provided by REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus score is labeled Likely Pathogenic. FoldX, Foldetta, and premPS give uncertain results. High‑accuracy tools: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment 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	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-8.535	Likely Pathogenic	0.689	Likely Pathogenic	Likely Benign	1.04	Ambiguous	0.1	0.15	Likely Benign	0.60	Ambiguous	0.75	Ambiguous	0.235	Likely Benign	-6.80	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.34	Benign	0.00	Affected			0.3159	0.3475		1	-1	3.4	-26.04
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.593T>G	L198R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198R 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 a 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, PROVEAN). Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence from multiple in‑silico predictors indicates 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.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-15.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.2	1.56	Ambiguous	1.15	Ambiguous	0.69	Ambiguous	0.410	Likely Benign	-4.98	Deleterious	0.982	Probably Damaging	0.648	Possibly Damaging	3.34	Benign	0.00	Affected			0.1180	0.0719		-3	-2	-8.3	43.03
c.1247T>C	L416P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and the SGM Consensus). High‑accuracy methods specifically indicate pathogenicity: 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 predictions are inconclusive. Based on the overall consensus of the majority of tools and the high‑accuracy methods, the variant is most likely pathogenic, which is consistent with the lack of ClinVar reporting and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.859	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.59	Destabilizing	0.1	6.23	Destabilizing	4.41	Destabilizing	1.27	Destabilizing	0.284	Likely Benign	-3.56	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.35	Benign	0.21	Tolerated			0.3589	0.1353		-3	-3	-5.4	-16.04
c.1247T>G	L416R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L416R missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools (FoldX, 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) also leans toward benign, while Foldetta remains uncertain. Overall, the majority of reliable predictors classify the variant as benign, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.600	Likely Pathogenic	0.511	Ambiguous	Likely Benign	0.71	Ambiguous	0.0	0.97	Ambiguous	0.84	Ambiguous	0.84	Ambiguous	0.238	Likely Benign	-2.05	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.35	Benign	0.43	Tolerated			0.1445	0.0702		-3	-2	-8.3	43.03
c.1256A>T	E419V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, FATHMM, and premPS, whereas pathogenic predictions arise from 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 further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from the high‑accuracy tools contradicts the pathogenic prediction. Overall, the majority of computational evidence points to a pathogenic effect, which is consistent with the lack of ClinVar reporting and gnomAD absence, suggesting the variant is most likely pathogenic. 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											-12.290	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.45	Likely Benign	0.0	1.41	Ambiguous	0.93	Ambiguous	0.27	Likely Benign	0.494	Likely Benign	-6.55	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.35	Benign	0.01	Affected			0.0953	0.6834		-2	-2	7.7	-29.98
c.1333G>A	E445K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E445K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic calls arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. When high‑accuracy methods are considered separately, 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 benign. Overall, the majority of evidence—including the high‑accuracy tools—supports a pathogenic effect. This conclusion does not conflict with 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	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-15.371	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.02	Likely Benign	0.0	0.02	Likely Benign	0.02	Likely Benign	0.46	Likely Benign	0.524	Likely Pathogenic	-3.82	Deleterious	0.991	Probably Damaging	0.951	Probably Damaging	3.35	Benign	0.02	Affected			0.1784	0.5311		0	1	-0.4	-0.94
c.1345A>G	S449G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449G is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (variant ID 6‑33438250‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as “Likely Benign,” and Foldetta as uncertain. Overall, the majority of evidence points to a benign 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 Benign	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000					Uncertain		1	6-33438250-A-G	3	1.86e-6	-5.936	Likely Benign	0.071	Likely Benign	Likely Benign	0.47	Likely Benign	0.0	0.55	Ambiguous	0.51	Ambiguous	0.85	Ambiguous	0.116	Likely Benign	-2.32	Neutral	0.948	Possibly Damaging	0.124	Benign	3.35	Benign	0.13	Tolerated	3.37	32	0.2600	0.3718		0	1	0.4	-30.03
c.1369A>G	S457G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S457G 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: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are 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, 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 S457G. 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	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-9.154	Likely Pathogenic	0.811	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.0	0.87	Ambiguous	0.87	Ambiguous	0.65	Ambiguous	0.382	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	3.35	Benign	0.13	Tolerated			0.2735	0.4074		1	0	0.4	-30.03
c.1372A>C	T458P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T458P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b, and the SGM‑Consensus) all predict a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as 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, also predicts a pathogenic effect. No prediction or folding stability result is missing or inconclusive. 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 entry for this variant. 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											-13.547	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.05	Destabilizing	0.2	5.36	Destabilizing	4.21	Destabilizing	0.78	Ambiguous	0.557	Likely Pathogenic	-5.33	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.06	Tolerated			0.2098	0.5395		0	-1	-0.9	-3.99
c.1378A>C	K460Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K460Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive include FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments give a pathogenic consensus from the SGM method (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and an uncertain result from AlphaMissense‑Optimized; Foldetta likewise reports no definitive stability change. Overall, the majority of evidence points toward 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	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-9.404	Likely Pathogenic	0.793	Likely Pathogenic	Ambiguous	0.71	Ambiguous	0.0	0.86	Ambiguous	0.79	Ambiguous	0.86	Ambiguous	0.312	Likely Benign	-3.15	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.14	Tolerated			0.4523	0.1454		1	1	0.4	-0.04
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.1387G>C	D463H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D463H is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, FoldX, SIFT, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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 effect: AlphaMissense‑Optimized predicts Pathogenic, SGM Consensus confirms Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains Uncertain. No evidence from ClinVar contradicts these findings. Overall, the preponderance of computational evidence indicates that D463H is most likely pathogenic. 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											-13.151	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	0.85	Ambiguous	0.53	Ambiguous	0.57	Ambiguous	0.356	Likely Benign	-5.96	Deleterious	0.996	Probably Damaging	0.852	Possibly Damaging	3.35	Benign	0.11	Tolerated			0.1341	0.6156		1	-1	0.3	22.05
c.1387G>T	D463Y 2D 3DClick to see structure in 3D Viewer AIClinVar reports no entry for this SynGAP1 D463Y variant, and it 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 PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from 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 (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of conventional tools lean toward pathogenicity, while the high‑accuracy Foldetta suggests benign. Thus, the variant is most likely pathogenic based on the prevailing 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	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-14.387	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	-0.14	Likely Benign	0.1	0.77	Ambiguous	0.32	Likely Benign	0.07	Likely Benign	0.399	Likely Benign	-7.95	Deleterious	0.998	Probably Damaging	0.904	Possibly Damaging	3.35	Benign	0.14	Tolerated			0.0540	0.6213		-4	-3	2.2	48.09
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.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.1614G>C	E538D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports benign. Consequently, the variant is most likely benign, and this prediction does not contradict the ClinVar status (no ClinVar entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-2.355	Likely Benign	0.112	Likely Benign	Likely Benign	0.32	Likely Benign	0.0	0.09	Likely Benign	0.21	Likely Benign	0.16	Likely Benign	0.122	Likely Benign	-0.88	Neutral	0.002	Benign	0.005	Benign	3.35	Benign	0.30	Tolerated			0.1801	0.2352		3	2	0.0	-14.03
c.1614G>T	E538D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports benign. Consequently, the variant is most likely benign, and this prediction does not contradict the ClinVar status (no ClinVar entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-2.355	Likely Benign	0.112	Likely Benign	Likely Benign	0.32	Likely Benign	0.0	0.09	Likely Benign	0.21	Likely Benign	0.16	Likely Benign	0.122	Likely Benign	-0.88	Neutral	0.002	Benign	0.005	Benign	3.35	Benign	0.30	Tolerated			0.1801	0.2352		3	2	0.0	-14.03
c.1771G>C	A591P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A591P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely converge on a pathogenic effect: pathogenic predictions come from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). Benign predictions are limited to REVEL and FATHMM. High‑accuracy assessments reinforce the pathogenic view: 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 indicates pathogenic. Consequently, the variant is most likely pathogenic, a conclusion that contrasts with its ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000					Uncertain		1				-14.479	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	3.78	Destabilizing	0.3	7.29	Destabilizing	5.54	Destabilizing	1.45	Destabilizing	0.404	Likely Benign	-4.41	Deleterious	0.995	Probably Damaging	0.853	Possibly Damaging	3.35	Benign	0.01	Affected	3.37	35	0.1872	0.3087		1	-1	-3.4	26.04	191.5	-10.1	0.2	0.1	0.4	0.1	X							Potentially Pathogenic	The methyl group of the Ala591 side chain, located in the middle of an α helix (res. Glu582-Met603), packs against hydrophobic residues (e.g., Ile483, Phe484) of an opposing partially helical loop (res. Phe476-Asn487).In the variant simulations, Pro591 lacks a free backbone amide group and, therefore, cannot form a hydrogen bond with the backbone carbonyl of Arg587 as Ala591 does in the WT. This notably weakens the α helix integrity and compromises the continuity of the helix. In reality, the effect on the structure during protein folding could be more severe.
c.1772C>T	A591V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A591V missense variant is not reported in ClinVar and is present in gnomAD (ID 6‑33440824‑C‑T). Functional prediction tools show discordant results: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, 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 (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains Likely Pathogenic. Overall, the majority of evidence points toward a pathogenic effect, and this assessment 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	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000								6-33440824-C-T	2	1.24e-6	-12.282	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	1.35	Ambiguous	0.4	0.98	Ambiguous	1.17	Ambiguous	0.86	Ambiguous	0.321	Likely Benign	-3.79	Deleterious	0.970	Probably Damaging	0.373	Benign	3.35	Benign	0.02	Affected	3.37	35	0.1128	0.4228		0	0	2.4	28.05
c.1816A>G	S606G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S606G is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, 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 (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is treated as unavailable. Overall, the majority 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	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.281	Likely Pathogenic	0.603	Likely Pathogenic	Likely Benign	0.43	Likely Benign	0.1	1.42	Ambiguous	0.93	Ambiguous	0.84	Ambiguous	0.229	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	3.35	Benign	0.04	Affected			0.2286	0.3279		1	0	0.4	-30.03
c.1910C>A	S637Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637Y 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, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of individual predictors (seven versus five) lean toward pathogenicity, and the consensus‑based SGM‑Consensus also supports a likely pathogenic classification. Therefore, the variant is most likely pathogenic based on the available 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	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-12.633	Likely Pathogenic	0.770	Likely Pathogenic	Likely Benign	0.13	Likely Benign	0.1	1.52	Ambiguous	0.83	Ambiguous	0.50	Likely Benign	0.209	Likely Benign	-3.78	Deleterious	0.985	Probably Damaging	0.681	Possibly Damaging	3.35	Benign	0.00	Affected			0.0968	0.4071		-3	-2	-0.5	76.10
c.1910C>T	S637F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S637F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and yields a pathogenic verdict. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points toward 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	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-13.266	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	0.01	Likely Benign	0.1	0.96	Ambiguous	0.49	Likely Benign	0.49	Likely Benign	0.222	Likely Benign	-3.92	Deleterious	0.985	Probably Damaging	0.681	Possibly Damaging	3.35	Benign	0.01	Affected			0.0780	0.4126		-3	-2	3.6	60.10
c.1934T>G	F645C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645C 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 outcome: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, 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	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-9.182	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous	2.25	Destabilizing	0.1	2.44	Destabilizing	2.35	Destabilizing	1.38	Destabilizing	0.286	Likely Benign	-5.41	Deleterious	0.967	Probably Damaging	0.389	Benign	3.35	Benign	0.01	Affected			0.2421	0.1372		-4	-2	-0.3	-44.04
c.1946T>C	M649T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649T 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—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores 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 classifies the variant as pathogenic. Based on the collective 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.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-11.916	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.19	Destabilizing	0.2	3.45	Destabilizing	3.32	Destabilizing	1.92	Destabilizing	0.531	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.779	Possibly Damaging	3.35	Benign	0.00	Affected			0.1732	0.1615		-1	-1	-2.6	-30.09
c.1999A>G	I667V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I667V 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, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Only ESM1b predicts a pathogenic outcome; all other tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, Foldetta) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote. Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence points to 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	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-8.482	Likely Pathogenic	0.406	Ambiguous	Likely Benign	1.32	Ambiguous	0.0	1.06	Ambiguous	1.19	Ambiguous	0.85	Ambiguous	0.234	Likely Benign	-0.86	Neutral	0.341	Benign	0.052	Benign	3.35	Benign	0.15	Tolerated			0.1178	0.3059		4	3	-0.3	-14.03
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.2026A>T	S676C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen2_HumVar, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen2_HumDiv, SIFT, and ESM1b. Rosetta and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely benign, 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 Benign	GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-9.230	Likely Pathogenic	0.132	Likely Benign	Likely Benign	0.47	Likely Benign	0.1	0.77	Ambiguous	0.62	Ambiguous	0.15	Likely Benign	0.164	Likely Benign	-2.45	Neutral	0.959	Probably Damaging	0.431	Benign	3.35	Benign	0.01	Affected			0.1113	0.6352		0	-1	3.3	16.06
c.2047A>G	I683V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683V is listed in ClinVar with an uncertain significance and is present in gnomAD (6‑33441306‑A‑G). Across a panel of in silico predictors, the majority indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (derived from a majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only polyPhen‑2 HumDiv classifies the change as pathogenic. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote) is benign, and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive and therefore not considered evidence. No other tool provides a pathogenic signal. Consequently, the variant is most likely benign, and this assessment does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000					Uncertain		1	6-33441306-A-G	2	1.24e-6	-7.588	In-Between	0.138	Likely Benign	Likely Benign	0.90	Ambiguous	0.0	0.60	Ambiguous	0.75	Ambiguous	0.76	Ambiguous	0.112	Likely Benign	-0.78	Neutral	0.538	Possibly Damaging	0.080	Benign	3.35	Benign	0.14	Tolerated	3.42	17	0.1021	0.2898		4	3	-0.3	-14.03	215.6	29.1	0.0	0.0	-0.7	0.1						X		Potentially Benign	The sec-butyl side chain of Ile683, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is sterically packed against His453 and Glu688. In the variant simulations, the iso-propyl side chain of Val683 has similar size and physicochemical properties as Ile630 in the WT, and thus, it is able to maintain similar interactions in the inter-helix space. Consequently, no negative structural effects are observed during the simulations due to the residue swap.
c.2092G>C	E698Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698Q is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. 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 benign. No prediction or folding stability result is missing or inconclusive. Overall, the evidence is split, with an equal number of benign and pathogenic calls; the high‑accuracy tools lean toward benign but are not definitive. Thus, the variant’s pathogenicity remains uncertain and 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	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-8.369	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	0.00	Likely Benign	0.1	0.35	Likely Benign	0.18	Likely Benign	-0.02	Likely Benign	0.326	Likely Benign	-2.86	Deleterious	0.987	Probably Damaging	0.946	Probably Damaging	3.35	Benign	0.01	Affected			0.1029	0.3702		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.2094G>C	E698D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698D 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 SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. No predictions are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-6.716	Likely Benign	0.207	Likely Benign	Likely Benign	0.21	Likely Benign	0.1	0.35	Likely Benign	0.28	Likely Benign	0.16	Likely Benign	0.155	Likely Benign	-2.45	Neutral	0.977	Probably Damaging	0.921	Probably Damaging	3.35	Benign	0.03	Affected			0.1643	0.2597		3	2	0.0	-14.03
c.2094G>T	E698D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698D 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 SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. No predictions are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-6.716	Likely Benign	0.207	Likely Benign	Likely Benign	0.21	Likely Benign	0.1	0.35	Likely Benign	0.28	Likely Benign	0.16	Likely Benign	0.155	Likely Benign	-2.45	Neutral	0.977	Probably Damaging	0.921	Probably Damaging	3.35	Benign	0.03	Affected			0.1643	0.2597		3	2	0.0	-14.03
c.2099T>G	L700R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L700R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, 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 inconclusive, SGM Consensus remains Likely Pathogenic, and Foldetta predicts a destabilizing, pathogenic effect. Overall, the preponderance 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	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-12.389	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.82	Ambiguous	0.1	4.19	Destabilizing	3.01	Destabilizing	1.89	Destabilizing	0.485	Likely Benign	-4.29	Deleterious	0.728	Possibly Damaging	0.249	Benign	3.35	Benign	0.01	Affected			0.1210	0.0488		-3	-2	-8.3	43.03
c.2122C>G	L708V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results are from FoldX (uncertain) and Foldetta (uncertain). High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta remains uncertain. Overall, the evidence strongly indicates that the variant is most likely benign, 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	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-4.361	Likely Benign	0.097	Likely Benign	Likely Benign	1.59	Ambiguous	0.0	0.12	Likely Benign	0.86	Ambiguous	-0.02	Likely Benign	0.122	Likely Benign	-0.23	Neutral	0.158	Benign	0.035	Benign	3.35	Benign	0.94	Tolerated			0.1094	0.2460		2	1	0.4	-14.03
c.2132T>G	L711R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L711R lies 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 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	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000											-14.009	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.71	Destabilizing	0.0	3.98	Destabilizing	3.85	Destabilizing	2.13	Destabilizing	0.432	Likely Benign	-5.71	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.35	Benign	0.00	Affected			0.1345	0.0488		-3	-2	-8.3	43.03
c.2134G>C	G712R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G712R 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—PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, Rosetta, and the SGM Consensus—classify it as pathogenic. Two tools, FoldX and premPS, return uncertain results. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta each predict a deleterious effect. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation. 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											-11.776	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	1.75	Ambiguous	0.0	4.68	Destabilizing	3.22	Destabilizing	0.82	Ambiguous	0.458	Likely Benign	-6.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.01	Affected			0.1229	0.4482		-3	-2	-4.1	99.14
c.2147G>A	R716Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R716Q is listed in ClinVar with an uncertain significance (ClinVar ID 411585.0) and is present in gnomAD (ID 6‑33441612‑G‑A). Functional prediction tools that report a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b, while premPS is inconclusive. 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. 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.		GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000					Conflicting		2	6-33441612-G-A	4	2.48e-6	-8.338	Likely Pathogenic	0.308	Likely Benign	Likely Benign	-0.01	Likely Benign	0.0	0.47	Likely Benign	0.23	Likely Benign	0.58	Ambiguous	0.210	Likely Benign	-3.14	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.35	Benign	0.02	Affected	3.50	9	0.2834	0.2180		1	1	1.0	-28.06	250.0	48.9	0.0	0.0	-0.5	0.0						X		Uncertain	The guanidinium group of Arg716, located on the outer surface of an α-helix (res. Leu714-Arg726), forms a salt bridge with the carboxylate group of Asp720. In the variant simulations, the carboxamide group of Gln716 also forms a hydrogen bond with the carboxylate group of Asp720, although this bond is weaker than the Arg716 salt bridge in the WT. Overall, no adverse effects on the protein structure are observed in the simulations. However, because the model ends abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
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.1255G>A	E419K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419K 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, premPS, SIFT, and FATHMM. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Foldetta and Rosetta give uncertain results and are not counted in either group. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus predicts likely pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact for E419K. 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	0.371949	Uncertain	0.961	0.261	0.000											-12.257	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.01	Likely Benign	0.1	1.30	Ambiguous	0.66	Ambiguous	-0.03	Likely Benign	0.399	Likely Benign	-3.75	Deleterious	0.998	Probably Damaging	0.975	Probably Damaging	3.36	Benign	0.07	Tolerated			0.2759	0.6899		0	1	-0.4	-0.94
c.1315C>G	L439V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; premPS is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of predictions (8 benign vs. 5 pathogenic) favor a benign classification, and this consensus does not contradict the absence of ClinVar evidence. Thus, based on current computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-6.340	Likely Benign	0.279	Likely Benign	Likely Benign	2.34	Destabilizing	0.2	2.40	Destabilizing	2.37	Destabilizing	0.91	Ambiguous	0.121	Likely Benign	-1.13	Neutral	0.976	Probably Damaging	0.941	Probably Damaging	3.36	Benign	0.12	Tolerated			0.1272	0.2628		2	1	0.4	-14.03
c.1328G>T	G443V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443V 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, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Overall, the majority of evidence points to a benign impact for G443V, 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 Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-4.130	Likely Benign	0.274	Likely Benign	Likely Benign	0.17	Likely Benign	0.2	-2.19	Stabilizing	-1.01	Ambiguous	0.21	Likely Benign	0.099	Likely Benign	-2.90	Deleterious	0.585	Possibly Damaging	0.195	Benign	3.36	Benign	0.12	Tolerated			0.1089	0.3375		-1	-3	4.6	42.08
c.1336G>A	E446K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446K is not reported in ClinVar (ClinVar status: not present) and is found in gnomAD (ID 6‑33438241‑G‑A). Prediction tools that agree on a benign effect include only FATHMM. Tools that agree on a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy methods give the following: AlphaMissense‑Optimized is uncertain; SGM‑Consensus indicates likely pathogenic; Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, 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	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000								6-33438241-G-A	1	6.19e-7	-14.140	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.4	1.57	Ambiguous	1.19	Ambiguous	0.81	Ambiguous	0.518	Likely Pathogenic	-3.75	Deleterious	0.994	Probably Damaging	0.975	Probably Damaging	3.36	Benign	0.01	Affected	3.38	31	0.2141	0.6511		1	0	-0.4	-0.94
c.1366C>A	Q456K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q456K is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; 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 outputs) as Benign. Overall, the majority of tools (six pathogenic vs five benign) and the SGM‑Consensus result point toward a pathogenic interpretation, while Foldetta suggests stability‑preserving benignity. Thus, the variant is most likely pathogenic based on current 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	GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-13.768	Likely Pathogenic	0.806	Likely Pathogenic	Ambiguous	0.21	Likely Benign	0.1	0.23	Likely Benign	0.22	Likely Benign	0.78	Ambiguous	0.391	Likely Benign	-3.75	Deleterious	0.969	Probably Damaging	0.875	Possibly Damaging	3.36	Benign	0.13	Tolerated			0.1321	0.2547		1	1	-0.4	0.04
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.1390T>G	F464V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F464V variant is listed in ClinVar with an “Uncertain” status (ClinVar ID 1716596.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM; all other evaluated algorithms (REVEL, 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 (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, 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.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000					Uncertain		1				-12.254	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.61	Destabilizing	0.1	2.89	Destabilizing	3.25	Destabilizing	1.40	Destabilizing	0.592	Likely Pathogenic	-6.96	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	3.36	Benign	0.04	Affected	3.37	34	0.1587	0.2219		-1	-1	1.4	-48.04	210.1	40.5	-0.1	0.0	-0.9	0.3							X	Potentially Pathogenic	The phenyl ring of Phe464, located in the middle of an α helix (res. Ala461–Phe476), packs against hydrophobic residues (e.g., Met468, Leu451, Leu455, and Tyr428) in the inter-helix space formed with two other α helices (res. Asn440-Lys460 and res. Pro413-Glu436). The iso-propyl side chain of Val464 is similarly hydrophobic but considerably smaller than the original phenyl ring of Phe464. To compensate for the size difference, neighboring residues need to fill in the gap in the variant simulations.The phenolic side chain of Tyr428, located at the middle bend of an α helix (res. Glu436-Pro413), assumes a new position in the inter-helix space or rotates inward next to the third α helix (res. Asn440-Lys460) when the stable H-bond between Tyr428 and Asp467 seen in the WT simulations breaks. The residue swap also leads to the loss of the methionine-aromatic interaction between the Met468 and Phe464 side chains, which could weaken the integrity of the parent α helix (res. Ala461-Phe476). Although the simulations likely underestimate the full adverse effect of the introduced mutation during folding, the two opposing α helices (res. Ala461–Phe476 and res. Glu436-Pro413) move substantially closer to each other in the variant simulations.
c.1503T>G	I501M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Predictions that are inconclusive or unavailable are FoldX, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Taken together, the majority of evidence points to a benign impact for I501M. 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 Benign	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-7.452	In-Between	0.259	Likely Benign	Likely Benign	1.32	Ambiguous	0.2	-0.19	Likely Benign	0.57	Ambiguous	0.95	Ambiguous	0.294	Likely Benign	-2.32	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.36	Benign	0.01	Affected			0.0680	0.1589		2	1	-2.6	18.03
c.1600T>G	S534A 2D 3DClick to see structure in 3D Viewer AISynGAP1 S534A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenicity. High‑accuracy methods reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. No evidence suggests a deleterious effect. Therefore, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-4.691	Likely Benign	0.082	Likely Benign	Likely Benign	0.01	Likely Benign	0.0	-0.01	Likely Benign	0.00	Likely Benign	0.11	Likely Benign	0.163	Likely Benign	-1.70	Neutral	0.880	Possibly Damaging	0.994	Probably Damaging	3.36	Benign	0.42	Tolerated			0.5042	0.3131	Weaken	1	1	2.6	-16.00
c.1613A>C	E538A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538A 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. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts likely pathogenic, and Foldetta predicts benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of tools (7 pathogenic vs 6 benign) lean toward a pathogenic interpretation, and this 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	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-9.888	Likely Pathogenic	0.770	Likely Pathogenic	Likely Benign	0.33	Likely Benign	0.0	-0.06	Likely Benign	0.14	Likely Benign	0.16	Likely Benign	0.269	Likely Benign	-4.66	Deleterious	0.944	Possibly Damaging	0.761	Possibly Damaging	3.36	Benign	0.05	Affected			0.3995	0.4187		0	-1	5.3	-58.04
c.175C>G	L59V 2D AIThe SynGAP1 missense variant L59V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. 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 for this variant. This conclusion is consistent with the absence of a ClinVar classification, 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		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-4.465	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.049	Likely Benign	-1.15	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	3.36	Benign	0.00	Affected			0.1508	0.3217		2	1	0.4	-14.03
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.1976C>G	S659C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659C 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. Two tools (Rosetta and ESM1b) return uncertain results and are not counted as evidence for either side. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Based on the collective predictions, 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	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-7.133	In-Between	0.161	Likely Benign	Likely Benign	0.09	Likely Benign	0.0	0.69	Ambiguous	0.39	Likely Benign	0.36	Likely Benign	0.173	Likely Benign	-4.12	Deleterious	0.981	Probably Damaging	0.397	Benign	3.36	Benign	0.04	Affected			0.1130	0.5384		0	-1	3.3	16.06
c.1979T>C	M660T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660T is catalogued in gnomAD (ID 6‑33441238‑T‑C) but has no ClinVar entry, so its clinical status is currently unreported. In silico prediction tools largely agree that the substitution is deleterious: 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 effect. High‑accuracy assessments reinforce the pathogenic 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 prediction or folding result is 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 none is available. 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								6-33441238-T-C	1	6.20e-7	-9.791	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	3.62	Destabilizing	0.1	2.05	Destabilizing	2.84	Destabilizing	1.91	Destabilizing	0.561	Likely Pathogenic	-5.99	Deleterious	0.967	Probably Damaging	0.633	Possibly Damaging	3.36	Benign	0.02	Affected	3.38	28	0.1811	0.1630		-1	-1	-2.6	-30.09
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.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.2017C>G	L673V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673V 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 SGM‑Consensus (Likely Benign), REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Benign, and Foldetta as pathogenic, yielding one pathogenic versus two benign predictions. Overall, the majority of evidence points to a benign impact, 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 Benign	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-8.132	Likely Pathogenic	0.099	Likely Benign	Likely Benign	2.18	Destabilizing	0.3	2.10	Destabilizing	2.14	Destabilizing	0.10	Likely Benign	0.017	Likely Benign	-0.58	Neutral	0.016	Benign	0.003	Benign	3.36	Benign	0.28	Tolerated			0.1448	0.3777		2	1	0.4	-14.03
c.2018T>G	L673R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L673R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote). FoldX and Foldetta are inconclusive. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM Consensus, and an uncertain outcome from Foldetta. Overall, the majority of evidence points toward pathogenicity, and this conclusion does not conflict with 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	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-14.474	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	1.10	Ambiguous	0.2	2.04	Destabilizing	1.57	Ambiguous	1.23	Destabilizing	0.178	Likely Benign	-3.81	Deleterious	0.991	Probably Damaging	0.433	Benign	3.36	Benign	0.03	Affected			0.1348	0.1015		-3	-2	-8.3	43.03
c.2050G>C	D684H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, 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 are inconclusive or missing. Based on the overwhelming majority of pathogenic predictions, 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.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000					Uncertain		1				-14.194	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.36	Destabilizing	1.0	2.95	Destabilizing	3.16	Destabilizing	0.55	Ambiguous	0.613	Likely Pathogenic	-6.98	Deleterious	1.000	Probably Damaging	0.972	Probably Damaging	3.36	Benign	0.00	Affected	3.42	17	0.1344	0.6618		-1	1	0.3	22.05
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.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.394T>A	F132I 2D AISynGAP1 missense variant F132I 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, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign) and Foldetta results are unavailable. Because the majority of consensus tools predict benign and no ClinVar evidence contradicts this, the variant is most likely benign, although the pathogenic signal from AlphaMissense‑Optimized and the inconclusive SGM Consensus leave some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-6.245	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-3.23	Deleterious	0.084	Benign	0.020	Benign	3.36	Benign	0.00	Affected			0.2306	0.1698		1	0	1.7	-34.02
c.1253A>C	K418T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K418T variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, FATHMM, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of tools (10 pathogenic vs. 5 benign) support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar record exists. 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											-11.994	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.1	0.55	Ambiguous	0.47	Likely Benign	0.41	Likely Benign	0.392	Likely Benign	-5.36	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.37	Benign	0.04	Affected			0.1975	0.1894		0	-1	3.2	-27.07
c.1253A>G	K418R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418R 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, ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Optimized. Tools that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus methods give a benign verdict: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign (3 benign vs. 1 pathogenic); and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. premPS is uncertain and therefore not considered evidence. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely benign, 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 Benign	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-6.809	Likely Benign	0.635	Likely Pathogenic	Likely Benign	-0.18	Likely Benign	0.1	0.12	Likely Benign	-0.03	Likely Benign	0.56	Ambiguous	0.229	Likely Benign	-2.46	Neutral	0.994	Probably Damaging	0.962	Probably Damaging	3.37	Benign	0.04	Affected			0.4384	0.1151		3	2	-0.6	28.01
c.1273A>C	T425P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425P 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, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as deleterious, while only FATHMM predicts a benign outcome; premPS is uncertain. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. Taken together, the overwhelming majority of evidence supports a pathogenic classification, 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	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-12.318	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.81	Destabilizing	0.3	6.49	Destabilizing	4.65	Destabilizing	0.77	Ambiguous	0.512	Likely Pathogenic	-5.16	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.03	Affected			0.1815	0.3469		0	-1	-0.9	-3.99
c.1297G>C	A433P 2D 3DClick to see structure in 3D Viewer AISynGAP1 A433P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, SIFT, and FATHMM. Those that predict pathogenicity comprise FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. The remaining tools, premPS and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the lack of ClinVar annotation and gnomAD absence. Therefore, 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	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-9.887	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	2.48	Destabilizing	0.0	7.09	Destabilizing	4.79	Destabilizing	0.55	Ambiguous	0.217	Likely Benign	-2.64	Deleterious	0.998	Probably Damaging	0.820	Possibly Damaging	3.37	Benign	0.07	Tolerated			0.1471	0.4150		1	-1	-3.4	26.04
c.1321G>T	V441F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V441F missense variant is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools lean toward a benign interpretation, and the high‑accuracy predictions are split but favor benign. Thus, the variant is most likely benign based on 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	GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-13.519	Likely Pathogenic	0.653	Likely Pathogenic	Likely Benign	-0.26	Likely Benign	0.0	0.32	Likely Benign	0.03	Likely Benign	0.54	Ambiguous	0.355	Likely Benign	-4.22	Deleterious	0.992	Probably Damaging	0.658	Possibly Damaging	3.37	Benign	0.08	Tolerated			0.0670	0.3269		-1	-1	-1.4	48.04
c.1325A>T	K442I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K442I 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 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 assessments are: 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 benign. Overall, the majority of predictions, including the two high‑accuracy pathogenic calls, 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.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-14.921	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.16	Likely Benign	0.1	-0.16	Likely Benign	0.00	Likely Benign	0.30	Likely Benign	0.350	Likely Benign	-6.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.02	Affected			0.0943	0.3073		-2	-3	8.4	-15.01
c.1327G>T	G443C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools are inconclusive: Foldetta is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta remains uncertain. Overall, the consensus of the majority of evidence points to a benign impact for G443C, 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 Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-4.308	Likely Benign	0.208	Likely Benign	Likely Benign	-0.06	Likely Benign	0.0	-0.95	Ambiguous	-0.51	Ambiguous	-0.10	Likely Benign	0.260	Likely Benign	-2.94	Deleterious	0.977	Probably Damaging	0.504	Possibly Damaging	3.37	Benign	0.16	Tolerated			0.1258	0.2782		-3	-3	2.9	46.09
c.1339G>A	V447I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V447I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate a benign or likely benign outcome. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Thus, the variant is most likely benign, 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 Benign	GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000											-5.067	Likely Benign	0.167	Likely Benign	Likely Benign	-0.33	Likely Benign	0.1	0.27	Likely Benign	-0.03	Likely Benign	-0.44	Likely Benign	0.117	Likely Benign	-0.06	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.37	Benign	0.28	Tolerated			0.0625	0.3059		4	3	0.3	14.03
c.1340T>C	V447A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V447A missense variant is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenicity. No predictions are missing or inconclusive. Based on the overall distribution of predictions, 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	GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000											-9.852	Likely Pathogenic	0.692	Likely Pathogenic	Likely Benign	2.18	Destabilizing	0.0	2.72	Destabilizing	2.45	Destabilizing	1.56	Destabilizing	0.266	Likely Benign	-2.84	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.15	Tolerated			0.2456	0.2124		0	0	-2.4	-28.05
c.1346G>A	S449N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449N is not reported in ClinVar (ClinVar status: not listed) but is present in the gnomAD database (gnomAD ID: 6‑33438251‑G‑A). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from premPS (uncertain) and ESM1b (uncertain). High‑accuracy assessments reinforce the benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Based on the collective evidence, 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	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000								6-33438251-G-A	1	6.19e-7	-7.692	In-Between	0.210	Likely Benign	Likely Benign	0.38	Likely Benign	0.1	-0.03	Likely Benign	0.18	Likely Benign	0.81	Ambiguous	0.070	Likely Benign	-2.31	Neutral	0.372	Benign	0.026	Benign	3.37	Benign	0.18	Tolerated	3.37	32	0.1085	0.3767		1	1	-2.7	27.03
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.1368G>C	Q456H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456H 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 AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Foldetta, and ESM1b. 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 lean toward a benign impact, and this does not contradict the lack of ClinVar annotation. Thus, based on the available computational evidence, the variant is most likely benign, though a high‑accuracy consensus suggests a possible pathogenic effect that warrants further investigation. 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											-7.993	In-Between	0.598	Likely Pathogenic	Likely Benign	0.74	Ambiguous	0.1	0.39	Likely Benign	0.57	Ambiguous	0.32	Likely Benign	0.214	Likely Benign	-4.07	Deleterious	0.996	Probably Damaging	0.974	Probably Damaging	3.37	Benign	0.19	Tolerated			0.0987	0.2358		3	0	0.3	9.01
c.1368G>T	Q456H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456H 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 AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Foldetta, and ESM1b. 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 lean toward a benign impact, and this does not contradict the lack of ClinVar annotation. Thus, based on the available computational evidence, the variant is most likely benign, though a high‑accuracy consensus suggests a possible pathogenic effect that warrants further investigation. 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											-7.993	In-Between	0.598	Likely Pathogenic	Likely Benign	0.74	Ambiguous	0.1	0.39	Likely Benign	0.57	Ambiguous	0.32	Likely Benign	0.214	Likely Benign	-4.07	Deleterious	0.996	Probably Damaging	0.974	Probably Damaging	3.37	Benign	0.19	Tolerated			0.0987	0.2358		3	0	0.3	9.01
c.1457A>T	E486V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, SIFT, FATHMM, and Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Uncertain results from FoldX and Rosetta are treated as unavailable. Overall, the majority of predictions support a pathogenic classification, and 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	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-15.115	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	-0.65	Ambiguous	-0.06	Likely Benign	0.31	Likely Benign	0.490	Likely Benign	-6.36	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.37	Benign	0.06	Tolerated			0.0493	0.6445		-2	-2	7.7	-29.98
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.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.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.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.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.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.1934T>C	F645S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F645S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while both the SGM Consensus and Foldetta predict pathogenicity. No evidence from ClinVar contradicts these findings. Overall, the preponderance of predictions supports a pathogenic classification for F645S. 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											-9.748	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	2.49	Destabilizing	0.2	2.30	Destabilizing	2.40	Destabilizing	1.57	Destabilizing	0.326	Likely Benign	-5.34	Deleterious	0.755	Possibly Damaging	0.112	Benign	3.37	Benign	0.03	Affected			0.3899	0.0547		-3	-2	-3.6	-60.10
c.1972G>T	G658C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658C 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. One tool, ESM1b, yields an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign (2 benign vs. 1 pathogenic, 1 uncertain), and Foldetta predicts a benign impact on protein stability. Overall, the majority of evidence points to 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	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-7.577	In-Between	0.170	Likely Benign	Likely Benign	0.05	Likely Benign	0.0	0.04	Likely Benign	0.05	Likely Benign	0.46	Likely Benign	0.146	Likely Benign	-3.49	Deleterious	0.989	Probably Damaging	0.544	Possibly Damaging	3.37	Benign	0.04	Affected			0.1509	0.3141		-3	-3	2.9	46.09
c.1997A>G	E666G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E666G is listed in ClinVar as Benign (ClinVar ID 1115026.0) and is present in gnomAD (ID 6‑33441256‑A‑G). Functional prediction tools that agree on pathogenicity include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. Only FATHMM predicts a benign effect. Predictions marked Uncertain (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. 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 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.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000					Likely Benign		1	6-33441256-A-G	10	6.20e-6	-12.261	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	1.57	Ambiguous	0.1	1.46	Ambiguous	1.52	Ambiguous	0.93	Ambiguous	0.522	Likely Pathogenic	-6.25	Deleterious	1.000	Probably Damaging	0.970	Probably Damaging	3.37	Benign	0.02	Affected	3.38	28	0.3051	0.4015		0	-2	3.1	-72.06	173.9	98.5	0.0	0.0	-0.7	0.0		X						Potentially Pathogenic	In the WT simulations, the carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669. In the variant simulations, the carbonyl group of Gly666 occasionally forms hydrogen bonds with Lys566 and Asn669. However, Gly666 lacks a side chain and thus cannot maintain as well-coordinated a hydrogen-bond network as Glu666 in the WT, which may affect the tertiary structure assembly.
c.2017C>A	L673I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The remaining tools (FoldX, Rosetta, Foldetta, ESM1b) return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Taken together, the majority of reliable predictors indicate a benign effect, and there is no conflict with ClinVar status (which has no entry). Therefore, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-7.823	In-Between	0.099	Likely Benign	Likely Benign	1.51	Ambiguous	0.2	1.89	Ambiguous	1.70	Ambiguous	-0.02	Likely Benign	0.036	Likely Benign	-0.14	Neutral	0.535	Possibly Damaging	0.112	Benign	3.37	Benign	0.47	Tolerated			0.0910	0.3689		2	2	0.7	0.00
c.2018T>C	L673P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673P 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, 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 Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts Pathogenic. Taken together, the overwhelming majority of predictions, including the high‑accuracy tools, classify the variant as pathogenic. 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	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-12.160	Likely Pathogenic	0.622	Likely Pathogenic	Likely Benign	2.41	Destabilizing	0.3	1.63	Ambiguous	2.02	Destabilizing	1.17	Destabilizing	0.207	Likely Benign	-4.10	Deleterious	1.000	Probably Damaging	0.978	Probably Damaging	3.37	Benign	0.02	Affected			0.3552	0.1474		-3	-3	-5.4	-16.04
c.2024A>T	N675I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675I is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools cluster into two groups: benign predictions come from REVEL, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and Rosetta give uncertain results and are treated as unavailable. High‑accuracy methods give mixed outcomes: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. Overall, the majority of tools (7/12) indicate pathogenicity, while 5/12 indicate benign. Thus, the variant is most likely pathogenic based on the current computational evidence, 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	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-13.254	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.1	-0.97	Ambiguous	0.02	Likely Benign	0.41	Likely Benign	0.338	Likely Benign	-7.37	Deleterious	0.999	Probably Damaging	0.955	Probably Damaging	3.37	Benign	0.00	Affected			0.0620	0.7188		-2	-3	8.0	-0.94
c.2032A>T	S678C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678C 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. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Tools with uncertain results are Rosetta and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (2 benign vs. 1 pathogenic, 1 uncertain), and Foldetta also predicts benign. No prediction or folding stability result is missing or inconclusive. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion 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.		GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-7.879	In-Between	0.095	Likely Benign	Likely Benign	0.21	Likely Benign	0.2	0.55	Ambiguous	0.38	Likely Benign	0.35	Likely Benign	0.094	Likely Benign	-3.31	Deleterious	0.947	Possibly Damaging	0.527	Possibly Damaging	3.37	Benign	0.01	Affected			0.1080	0.5875		0	-1	3.3	16.06
c.2051A>G	D684G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect largely agree on a deleterious outcome. Benign predictions come from premPS and FATHMM, whereas the remaining 12 tools—including REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify it as pathogenic. High‑accuracy methods reinforce this view: 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 reports pathogenic. No prediction is inconclusive or missing. 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	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-14.238	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.34	Destabilizing	1.0	4.07	Destabilizing	3.71	Destabilizing	-0.30	Likely Benign	0.561	Likely Pathogenic	-6.98	Deleterious	0.999	Probably Damaging	0.935	Probably Damaging	3.37	Benign	0.01	Affected			0.3686	0.5403		1	-1	3.1	-58.04
c.2052C>A	D684E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D684E missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. In contrast, a majority of predictors (SGM‑Consensus, FoldX, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; predictions from Rosetta and premPS are inconclusive and are treated as unavailable. 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 consensus of these 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	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-9.506	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.88	Destabilizing	0.9	1.48	Ambiguous	2.18	Destabilizing	0.66	Ambiguous	0.362	Likely Benign	-3.99	Deleterious	0.910	Possibly Damaging	0.210	Benign	3.37	Benign	0.01	Affected			0.1316	0.6187		3	2	0.0	14.03
c.2052C>G	D684E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684E is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of algorithms predict a deleterious effect: FoldX, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Two methods (Rosetta and premPS) returned uncertain results. High‑accuracy assessments further support a damaging impact: 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. Overall, the computational evidence overwhelmingly indicates that D684E is 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	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-9.506	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.88	Destabilizing	0.9	1.48	Ambiguous	2.18	Destabilizing	0.66	Ambiguous	0.362	Likely Benign	-3.99	Deleterious	0.910	Possibly Damaging	0.210	Benign	3.37	Benign	0.01	Affected			0.1316	0.6187		3	2	0.0	14.03
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.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.2092G>A	E698K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698K 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 comprise 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). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a benign impact. Because the high‑accuracy predictions are split, the overall evidence is inconclusive, but the majority of tools lean toward pathogenicity. The variant is therefore most likely pathogenic based on the preponderance of predictions, 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	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-8.881	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.23	Likely Benign	0.1	0.38	Likely Benign	0.31	Likely Benign	-0.07	Likely Benign	0.466	Likely Benign	-3.79	Deleterious	0.991	Probably Damaging	0.951	Probably Damaging	3.37	Benign	0.01	Affected			0.2218	0.4383		0	1	-0.4	-0.94
c.2095G>A	V699M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V699M is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441354‑G‑A). Across in silico predictors, benign calls are made by REVEL, Rosetta, Foldetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Predictions that are inconclusive (FoldX, premPS, AlphaMissense‑Default) are noted but not used as evidence. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports benign stability. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the ClinVar uncertain status but provides a stronger leaning toward benignity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000					Uncertain		2	6-33441354-G-A	8	4.96e-6	-8.869	Likely Pathogenic	0.484	Ambiguous	Likely Benign	-0.58	Ambiguous	0.1	0.29	Likely Benign	-0.15	Likely Benign	0.96	Ambiguous	0.276	Likely Benign	-2.18	Neutral	0.994	Probably Damaging	0.806	Possibly Damaging	3.37	Benign	0.03	Affected	3.47	10	0.0734	0.3071		2	1	-2.3	32.06	257.8	-47.2	0.0	0.0	0.9	0.1						X		Potentially Benign	The isopropyl side chain of Val699, located on an α-helix (res. Leu685-Gln702), packs against hydrophobic residues (e.g., Leu703, Leu696, Leu435, Leu439) in the inter-helix space. In the variant simulations, the thioether side chain of Met699 has similar physicochemical properties to Val699 in the WT, and thus, it is able to maintain similar interactions. Consequently, the mutation causes no apparent changes in the structure.
c.2096T>G	V699G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V699G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FATHMM and AlphaMissense‑Optimized, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict; and Foldetta also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, 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.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000											-11.912	Likely Pathogenic	0.481	Ambiguous	Likely Benign	2.22	Destabilizing	0.0	3.25	Destabilizing	2.74	Destabilizing	1.77	Destabilizing	0.514	Likely Pathogenic	-5.11	Deleterious	0.972	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.01	Affected			0.1830	0.2240		-1	-3	-4.6	-42.08
c.2115G>C	K705N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705N is listed in ClinVar (ID 872011.0) as Pathogenic and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, Rosetta, premPS, FATHMM) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default). Uncertain results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: 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, and Foldetta also yields an uncertain stability change. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, which aligns with its ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000					Likely Pathogenic		1				-9.767	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.0	0.37	Likely Benign	0.56	Ambiguous	0.44	Likely Benign	0.183	Likely Benign	-3.12	Deleterious	0.996	Probably Damaging	0.876	Possibly Damaging	3.37	Benign	0.02	Affected	3.47	10	0.2480	0.1124		1	0	0.4	-14.07	221.4	-20.2	0.0	0.0	0.0	0.1						X		Uncertain	The amino side chain of Lys705, located at the end and outer surface of an α-helix (res. Thr704-Gly712), does not form any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Asn705 briefly forms a salt bridge with Glu706. However, there is no apparent difference between the systems. Due to the model ending abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2115G>T	K705N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K705N is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Three tools (FoldX, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic”; AlphaMissense‑Optimized remains uncertain, and Foldetta is also uncertain. Overall, the balance of evidence favors a pathogenic effect for K705N, and this conclusion 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.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.767	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.0	0.37	Likely Benign	0.56	Ambiguous	0.44	Likely Benign	0.183	Likely Benign	-3.12	Deleterious	0.996	Probably Damaging	0.876	Possibly Damaging	3.37	Benign	0.02	Affected	3.47	10	0.2480	0.1124		1	0	0.4	-14.07	221.4	-20.2	0.0	0.0	0.0	0.1						X		Uncertain	The amino side chain of Lys705, located at the end and outer surface of an α-helix (res. Thr704-Gly712), does not form any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Asn705 briefly forms a salt bridge with Glu706. However, there is no apparent difference between the systems. Due to the model ending abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
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.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.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.1241T>G	M414R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. 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 damaging outcome: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus remains likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the preponderance of evidence indicates that M414R 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	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-13.404	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.17	Ambiguous	0.1	2.58	Destabilizing	1.88	Ambiguous	1.45	Destabilizing	0.525	Likely Pathogenic	-5.20	Deleterious	0.972	Probably Damaging	0.895	Possibly Damaging	3.38	Benign	0.03	Affected			0.1509	0.1037		0	-1	-6.4	24.99
c.1246C>A	L416I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L416I missense variant 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, premPS, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that remain inconclusive are FoldX, Rosetta, AlphaMissense‑Default, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the preponderance of evidence points to a benign effect. This conclusion is not contradicted by any ClinVar annotation, as the variant has no existing ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.613	Likely Pathogenic	0.396	Ambiguous	Likely Benign	0.57	Ambiguous	0.0	0.69	Ambiguous	0.63	Ambiguous	0.50	Likely Benign	0.127	Likely Benign	-1.28	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.38	Benign	0.37	Tolerated			0.1073	0.3480		2	2	0.7	0.00
c.1264G>C	E422Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422Q 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, PROVEAN, and FATHMM, while those that predict a pathogenic effect are SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to 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	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-9.460	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.0	0.21	Likely Benign	0.27	Likely Benign	-0.15	Likely Benign	0.208	Likely Benign	-2.26	Neutral	0.997	Probably Damaging	0.973	Probably Damaging	3.38	Benign	0.03	Affected			0.1045	0.4913		2	2	0.0	-0.98
c.1266G>C	E422D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E422D 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, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (six benign vs five pathogenic) lean toward a benign effect, but the two most accurate predictors and the consensus vote indicate a pathogenic tendency. Thus, the variant is most likely benign based on the broader tool set, 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.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-7.092	In-Between	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.0	-0.03	Likely Benign	0.18	Likely Benign	0.21	Likely Benign	0.199	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.38	Benign	0.07	Tolerated			0.1686	0.2864		3	2	0.0	-14.03
c.1266G>T	E422D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E422D 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, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (six benign vs five pathogenic) lean toward a benign effect, but the two most accurate predictors and the consensus vote indicate a pathogenic tendency. Thus, the variant is most likely benign based on the broader tool set, 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.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-7.092	In-Between	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.0	-0.03	Likely Benign	0.18	Likely Benign	0.21	Likely Benign	0.199	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.38	Benign	0.07	Tolerated			0.1686	0.2864		3	2	0.0	-14.03
c.1267T>G	Y423D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining tools—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 reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. 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	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-13.279	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	4.67	Destabilizing	0.1	4.79	Destabilizing	4.73	Destabilizing	1.78	Destabilizing	0.553	Likely Pathogenic	-8.28	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.04	Affected			0.3262	0.0412		-4	-3	-2.2	-48.09
c.1268A>G	Y423C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. The remaining tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), SGM‑Consensus as Likely Pathogenic, and Foldetta as Pathogenic. With the majority of evidence pointing to deleterious effects, 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	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-9.003	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	4.01	Destabilizing	0.1	4.49	Destabilizing	4.25	Destabilizing	1.84	Destabilizing	0.286	Likely Benign	-7.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.38	Benign	0.03	Affected			0.2381	0.1096		0	-2	3.8	-60.04
c.1278C>A	N426K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426K resides 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 include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, 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 benign effect. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unclassified. 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											-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	0.197	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			0.1906	0.2822		1	0	-0.4	14.07
c.1278C>G	N426K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426K is located in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, while those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect on protein stability. Overall, the majority of predictions lean toward pathogenicity, with a split in the most reliable methods. Therefore, the variant is most likely pathogenic based on the current computational evidence, 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	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	0.197	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			0.1906	0.2822		1	0	-0.4	14.07
c.1298C>G	A433G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach a consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. The protein‑folding stability method Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and is therefore treated as unavailable evidence. Overall, the collective predictions strongly suggest that the variant is most likely benign, 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 Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-5.044	Likely Benign	0.107	Likely Benign	Likely Benign	0.59	Ambiguous	0.0	1.21	Ambiguous	0.90	Ambiguous	0.70	Ambiguous	0.038	Likely Benign	-1.54	Neutral	0.035	Benign	0.014	Benign	3.38	Benign	0.15	Tolerated			0.1629	0.2919		1	0	-2.2	-14.03
c.1301T>A	V434D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign are SIFT and FATHMM; all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns a pathogenic score; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among pathogenic predictors and the corroborating high‑accuracy tools, 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	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-14.765	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	3.26	Destabilizing	0.0	3.33	Destabilizing	3.30	Destabilizing	1.78	Destabilizing	0.592	Likely Pathogenic	-5.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.13	Tolerated			0.1307	0.0741		-2	-3	-7.7	15.96
c.1322T>A	V441D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V441D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and Foldetta, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. FoldX and Rosetta are inconclusive, and AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show that the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, while Foldetta predicts benign stability. Overall, the balance of evidence leans toward pathogenicity, 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	GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-15.392	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	-0.57	Ambiguous	0.1	0.56	Ambiguous	-0.01	Likely Benign	1.15	Destabilizing	0.308	Likely Benign	-6.07	Deleterious	1.000	Probably Damaging	0.959	Probably Damaging	3.38	Benign	0.10	Tolerated			0.1232	0.0698		-2	-3	-7.7	15.96
c.1349C>A	A450E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A450E is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include SIFT and FATHMM, whereas the majority of tools predict it to be pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No predictions are inconclusive. Overall, the evidence strongly favors a pathogenic impact for A450E, which does not contradict the current ClinVar status of uncertain significance. 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					Uncertain		1				-16.578	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	3.86	Destabilizing	0.2	5.23	Destabilizing	4.55	Destabilizing	1.59	Destabilizing	0.653	Likely Pathogenic	-4.67	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.38	Benign	0.07	Tolerated	3.37	32	0.0823	0.1695		0	-1	-5.3	58.04	240.1	-82.6	0.0	0.0	0.7	0.0			X				X	Potentially Pathogenic	The methyl group of Ala450, located in an α helix (res. Asn440-Thr458), packs against hydrophobic residues in the inter-helix space (e.g., Leu692). In the variant simulations, the carboxylate group of the Glu450 side chain rotates outward, away from the hydrophobic niche, where it does not form any lasting salt bridges or H-bonds. Although the residue swap does not negatively affect the protein structure based on the simulations, it is possible that the introduction of the negatively charged residue adversely affects the folding process or tertiary assembly.
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.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.1726T>C	C576R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C576R is listed in ClinVar with an uncertain significance (ClinVar ID 2780076.0) 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 and 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 it pathogenic, the SGM‑Consensus (derived from the majority of high‑confidence predictors) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Taken together, the overwhelming majority of computational evidence indicates that C576R is likely pathogenic, a conclusion that is consistent with, but not in conflict with, the current ClinVar uncertain 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					Conflicting		2				-14.886	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	7.20	Destabilizing	1.0	4.09	Destabilizing	5.65	Destabilizing	1.64	Destabilizing	0.579	Likely Pathogenic	-10.88	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected	3.37	35	0.1887	0.1279		-3	-4	-7.0	53.05
c.1726T>G	C576G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome. When high‑accuracy methods are considered, AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenicity. No prediction is inconclusive or missing. Consequently, the variant is most likely pathogenic based on the consensus of available computational evidence, and this assessment does not contradict any ClinVar annotation (none). 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											-14.809	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.0	2.53	Destabilizing	2.10	Destabilizing	1.67	Destabilizing	0.586	Likely Pathogenic	-10.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.00	Affected			0.3269	0.2574		-3	-3	-2.9	-46.09
c.1727G>A	C576Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576Y is not reported in ClinVar and has no gnomAD allele. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized all classify the change as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; 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 pathogenicity. No tool yields an inconclusive result. Based on the consensus of available predictions, 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	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-13.891	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	8.77	Destabilizing	0.5	3.90	Destabilizing	6.34	Destabilizing	0.63	Ambiguous	0.612	Likely Pathogenic	-9.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected			0.1398	0.3009		0	-2	-3.8	60.04
c.1728C>G	C576W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576W 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 other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, with no contradiction to ClinVar status (which has no entry). 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											-14.796	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	13.87	Destabilizing	1.5	5.46	Destabilizing	9.67	Destabilizing	0.60	Ambiguous	0.473	Likely Benign	-10.01	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.38	Benign	0.00	Affected			0.1894	0.3017		-8	-2	-3.4	83.07
c.1816A>C	S606R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain outcomes are Foldetta, premPS, and Rosetta. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta remains inconclusive. Overall, the majority of high‑confidence predictions and the consensus vote indicate a pathogenic effect. Because ClinVar contains no entry for this variant, there is no contradiction between the computational evidence and clinical annotation. Thus, the variant is most likely pathogenic. 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											-12.900	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.4	1.80	Ambiguous	0.98	Ambiguous	0.82	Ambiguous	0.252	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.38	Benign	0.08	Tolerated			0.0819	0.2750		0	-1	-3.7	69.11
c.1818T>A	S606R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain outcomes are Foldetta, premPS, and Rosetta. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta remains inconclusive. Overall, the majority of high‑confidence predictions and the consensus vote indicate a pathogenic effect. Because ClinVar contains no entry for this variant, there is no contradiction between the computational evidence and clinical annotation. Thus, the variant is most likely pathogenic. 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											-12.900	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.4	1.80	Ambiguous	0.98	Ambiguous	0.82	Ambiguous	0.246	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.38	Benign	0.08	Tolerated			0.0819	0.2750		0	-1	-3.7	69.11
c.1818T>G	S606R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606R is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas a majority predict pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. High‑accuracy methods confirm the pathogenic trend: AlphaMissense‑Optimized is pathogenic, SGM Consensus is Likely Pathogenic, and Foldetta remains uncertain. Overall, the evidence points to the variant being 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	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.900	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.15	Likely Benign	0.4	1.80	Ambiguous	0.98	Ambiguous	0.82	Ambiguous	0.246	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.38	Benign	0.08	Tolerated			0.0819	0.2750		0	-1	-3.7	69.11
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.1973G>T	G658V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv; Rosetta’s output is uncertain and therefore not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. Taken together, the majority of reliable predictors indicate a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-6.815	Likely Benign	0.166	Likely Benign	Likely Benign	-0.07	Likely Benign	0.0	-0.71	Ambiguous	-0.39	Likely Benign	0.34	Likely Benign	0.117	Likely Benign	-3.23	Deleterious	0.841	Possibly Damaging	0.264	Benign	3.38	Benign	0.13	Tolerated			0.1337	0.3330		-1	-3	4.6	42.08
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.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.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.2102C>A	P701H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P701H 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Predictions that are uncertain or inconclusive are FoldX, Foldetta, premPS, and AlphaMissense‑Default. 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 balance of evidence favors a benign classification, and this conclusion does not contradict the ClinVar status, which contains no pathogenic assertion 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											-8.786	Likely Pathogenic	0.553	Ambiguous	Likely Benign	1.40	Ambiguous	0.0	-0.41	Likely Benign	0.50	Ambiguous	0.62	Ambiguous	0.141	Likely Benign	-2.12	Neutral	0.936	Possibly Damaging	0.539	Possibly Damaging	3.38	Benign	0.03	Affected			0.1495	0.3495		0	-2	-1.6	40.02
c.2107C>A	L703I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and Rosetta. Predictions that are uncertain or inconclusive (FoldX, Foldetta, premPS, AlphaMissense‑Default) are treated as unavailable. 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 high‑confidence tools predict a benign impact, and this conclusion does not contradict the ClinVar status, which has no pathogenic classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-9.332	Likely Pathogenic	0.345	Ambiguous	Likely Benign	1.44	Ambiguous	0.1	2.21	Destabilizing	1.83	Ambiguous	0.61	Ambiguous	0.108	Likely Benign	-1.50	Neutral	0.982	Probably Damaging	0.758	Possibly Damaging	3.38	Benign	0.00	Affected			0.0909	0.3079		2	2	0.7	0.00
c.2114A>C	K705T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705T 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	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-8.617	Likely Pathogenic	0.826	Likely Pathogenic	Ambiguous	0.60	Ambiguous	0.0	0.04	Likely Benign	0.32	Likely Benign	0.17	Likely Benign	0.272	Likely Benign	-4.05	Deleterious	0.995	Probably Damaging	0.991	Probably Damaging	3.38	Benign	0.02	Affected			0.1299	0.2612		0	-1	3.2	-27.07
c.2129A>T	K710M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K710M 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 REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. 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 individual predictors (seven pathogenic vs. six benign) and the SGM Consensus lean toward a pathogenic interpretation, while the high‑accuracy Foldetta result is contradictory. Based on the collective evidence, 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											-13.081	Likely Pathogenic	0.822	Likely Pathogenic	Ambiguous	-0.13	Likely Benign	0.0	0.28	Likely Benign	0.08	Likely Benign	0.20	Likely Benign	0.298	Likely Benign	-5.61	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.00	Affected			0.0835	0.3444		0	-1	5.8	3.02
c.2149C>G	L717V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Two tools predict a damaging effect: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Stability‑based methods (FoldX, Rosetta, Foldetta) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as inconclusive. Taken together, the majority of evidence points to a benign impact. 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.	Likely Benign	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-6.164	Likely Benign	0.308	Likely Benign	Likely Benign	1.53	Ambiguous	0.0	1.25	Ambiguous	1.39	Ambiguous	0.09	Likely Benign	0.119	Likely Benign	-0.25	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.38	Benign	0.51	Tolerated			0.1226	0.2489		2	1	0.4	-14.03
c.2186A>G	N729S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus also as benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625					Uncertain		1				-1.578	Likely Benign	0.066	Likely Benign	Likely Benign	0.14	Likely Benign	0.1	1.34	Ambiguous	0.74	Ambiguous	-0.36	Likely Benign	0.063	Likely Benign	-0.42	Neutral	0.221	Benign	0.027	Benign	3.38	Benign	0.93	Tolerated	3.59	7	0.3411	0.4854		1	1	2.7	-27.03
c.394T>G	F132V 2D AIThe SynGAP1 missense variant F132V 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 agree on a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic. 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 predictions indicate a pathogenic effect, 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.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-7.637	In-Between	0.979	Likely Pathogenic	Likely Pathogenic										0.328	Likely Benign	-3.86	Deleterious	0.084	Benign	0.034	Benign	3.38	Benign	0.00	Affected			0.2349	0.1725		-1	-1	1.4	-48.04
c.1247T>A	L416Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict benign. Only two tools, polyPhen‑2 (HumDiv and HumVar), predict a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta remains uncertain. Overall, the evidence strongly supports a benign classification for this variant, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-6.445	Likely Benign	0.234	Likely Benign	Likely Benign	1.17	Ambiguous	0.1	0.54	Ambiguous	0.86	Ambiguous	0.88	Ambiguous	0.187	Likely Benign	-1.07	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.46	Tolerated			0.1281	0.0860		-2	-2	-7.3	14.97
c.1261G>C	A421P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A421P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL, FATHMM, and polyPhen‑2 HumVar, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, 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, labels the variant as Likely Pathogenic. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also indicates Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, reports a pathogenic effect. Taken together, the overwhelming majority of evidence points to a pathogenic impact for A421P, 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	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-13.126	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.51	Destabilizing	0.2	8.77	Destabilizing	6.64	Destabilizing	1.17	Destabilizing	0.371	Likely Benign	-4.31	Deleterious	0.855	Possibly Damaging	0.420	Benign	3.39	Benign	0.04	Affected			0.1963	0.3343		1	-1	-3.4	26.04
c.1264G>A	E422K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422K missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic predictions are reported 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, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus also indicates Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the balance of evidence leans toward pathogenicity, and this assessment does not contradict 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	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-13.042	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.0	0.10	Likely Benign	0.20	Likely Benign	0.32	Likely Benign	0.346	Likely Benign	-3.52	Deleterious	0.998	Probably Damaging	0.975	Probably Damaging	3.39	Benign	0.04	Affected			0.1995	0.5129		0	1	-0.4	-0.94
c.1267T>C	Y423H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y423H 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 REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect comprise FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Default. AlphaMissense‑Optimized is reported as uncertain. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and therefore inconclusive, while Foldetta predicts a pathogenic impact. Overall, the majority of evaluated tools (10 pathogenic vs. 4 benign) support a pathogenic classification. 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.		GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-6.638	Likely Benign	0.873	Likely Pathogenic	Ambiguous	3.09	Destabilizing	0.1	2.44	Destabilizing	2.77	Destabilizing	1.66	Destabilizing	0.257	Likely Benign	-3.88	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.61	Tolerated			0.1603	0.0352		0	2	-1.9	-26.03
c.1271T>C	V424A 2D 3DClick to see structure in 3D Viewer AISynGAP1 V424A is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on benign impact are REVEL and FATHMM, whereas the remaining tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as unavailable, SGM‑Consensus as likely pathogenic, and Foldetta as pathogenic. Based on the collective evidence, the variant is most likely pathogenic; this conclusion is not contradicted by the ClinVar status. 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											-9.665	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	2.31	Destabilizing	0.1	2.54	Destabilizing	2.43	Destabilizing	2.10	Destabilizing	0.245	Likely Benign	-3.45	Deleterious	0.997	Probably Damaging	0.961	Probably Damaging	3.39	Benign	0.01	Affected			0.2105	0.1355		0	0	-2.4	-28.05
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.1301T>G	V434G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as pathogenic. Taken together, the overwhelming majority of evidence indicates a deleterious effect. Therefore, 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.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-12.519	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous	3.08	Destabilizing	0.0	4.37	Destabilizing	3.73	Destabilizing	1.91	Destabilizing	0.564	Likely Pathogenic	-5.16	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.07	Tolerated			0.1758	0.2408		-1	-3	-4.6	-42.08
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.1332G>C	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta’s stability assessment is uncertain and therefore not used as evidence. Overall, the preponderance of evidence points to a pathogenic effect for K444N. 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	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1332G>T	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N 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. Tools that predict a pathogenic effect include FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. There is no ClinVar annotation 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.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1334A>G	E445G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E445G missense variant 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 (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Predictions that are inconclusive or uncertain are 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, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E445G, 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	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-12.294	Likely Pathogenic	0.823	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.1	0.79	Ambiguous	0.80	Ambiguous	0.69	Ambiguous	0.523	Likely Pathogenic	-6.68	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.39	Benign	0.01	Affected			0.2446	0.4202		0	-2	3.1	-72.06
c.1921T>A	S641T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign. Rosetta also predicts a benign outcome, while FoldX and Foldetta are inconclusive (marked “Uncertain”). No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; Foldetta remains uncertain. Consequently, the variant is most likely benign, 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.	Likely Benign	GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000											-6.637	Likely Benign	0.087	Likely Benign	Likely Benign	0.83	Ambiguous	0.3	0.41	Likely Benign	0.62	Ambiguous	0.13	Likely Benign	0.043	Likely Benign	-1.50	Neutral	0.008	Benign	0.003	Benign	3.39	Benign	0.09	Tolerated			0.1505	0.5888		1	1	0.1	14.03
c.1922C>T	S641L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641L 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), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN 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 because it yields an equal split of benign and pathogenic calls. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000											-9.501	Likely Pathogenic	0.237	Likely Benign	Likely Benign	0.33	Likely Benign	0.3	-0.14	Likely Benign	0.10	Likely Benign	0.32	Likely Benign	0.103	Likely Benign	-4.33	Deleterious	0.115	Benign	0.014	Benign	3.39	Benign	0.07	Tolerated			0.1248	0.5376		-3	-2	4.6	26.08
c.1951G>A	E651K 2D AIThe SynGAP1 E651K missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign calls (REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic calls (PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default). Three tools (Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is uncertain; 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 stability outputs, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, 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	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-8.714	Likely Pathogenic	0.818	Likely Pathogenic	Ambiguous	0.11	Likely Benign	0.4	1.15	Ambiguous	0.63	Ambiguous	0.08	Likely Benign	0.211	Likely Benign	-2.92	Deleterious	0.921	Possibly Damaging	0.303	Benign	3.39	Benign	0.17	Tolerated			0.2768	0.5803		0	1	-0.4	-0.94
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.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.2015C>T	T672M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T672M is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441274‑C‑T). Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Rosetta and Foldetta report uncertain results, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta remain unavailable. Overall, the balance of evidence favors a benign effect, and this conclusion does not contradict the ClinVar uncertain status. 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					Conflicting		3	6-33441274-C-T	19	1.18e-5	-9.472	Likely Pathogenic	0.174	Likely Benign	Likely Benign	0.31	Likely Benign	0.4	1.52	Ambiguous	0.92	Ambiguous	0.41	Likely Benign	0.127	Likely Benign	-4.34	Deleterious	0.993	Probably Damaging	0.520	Possibly Damaging	3.39	Benign	0.00	Affected	3.40	25	0.1332	0.6677		-1	-1	2.6	30.09	231.9	-52.9	1.1	0.1	0.5	0.0		X				X		Potentially Pathogenic	The hydroxyl group of Thr672, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop itself, such as Lys566, Glu666, and Asn669. Met672 can only form a hydrogen bond with the amino group of the Lys566 side chain via its backbone carbonyl group. Nevertheless, the Lys566-Glu666 salt bridge forms intermittently. This is possible because Asn669 keeps the carboxylate group of Glu666 in the vicinity through hydrogen bonding, and the hydrophobic side chain of Met stays mostly rotated away from the salt bridge. Consequently, no drastic disruption of the hydrogen-bond network that keeps the loop close to the helices occurs in the variant simulations.
c.2023A>C	N675H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Predictions that are inconclusive are Foldetta and premPS. High‑accuracy methods give a benign result from AlphaMissense‑Optimized, a benign consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and an uncertain result from Foldetta. Taken together, the majority of evidence points to a benign impact, and this does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-5.593	Likely Benign	0.254	Likely Benign	Likely Benign	3.06	Destabilizing	1.1	-0.16	Likely Benign	1.45	Ambiguous	0.56	Ambiguous	0.186	Likely Benign	-2.62	Deleterious	0.999	Probably Damaging	0.929	Probably Damaging	3.39	Benign	0.04	Affected			0.1478	0.7478		2	1	0.3	23.04
c.2026A>G	S676G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676G 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, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. Two tools (ESM1b and premPS) returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta predicts a benign stability change. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence points to a benign impact. 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.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-7.249	In-Between	0.117	Likely Benign	Likely Benign	0.38	Likely Benign	0.1	0.25	Likely Benign	0.32	Likely Benign	0.67	Ambiguous	0.132	Likely Benign	-2.74	Deleterious	0.855	Possibly Damaging	0.100	Benign	3.39	Benign	0.02	Affected			0.2772	0.4342		1	0	0.4	-30.03
c.2050G>A	D684N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684N is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas the majority of tools predict a pathogenic outcome: 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). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus also reports it as likely pathogenic, and the Foldetta stability analysis is inconclusive. Protein‑stability predictors FoldX and Rosetta likewise return uncertain results. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the current ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000					Uncertain		1				-13.155	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	1.47	Ambiguous	0.8	1.76	Ambiguous	1.62	Ambiguous	0.37	Likely Benign	0.382	Likely Benign	-4.99	Deleterious	0.999	Probably Damaging	0.746	Possibly Damaging	3.39	Benign	0.01	Affected			0.1157	0.6373		2	1	0.0	-0.98
c.2069C>A	S690Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) 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. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus confirms a Likely Pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, with no contradiction to 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	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-14.051	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	11.45	Destabilizing	3.1	3.02	Destabilizing	7.24	Destabilizing	0.16	Likely Benign	0.381	Likely Benign	-5.76	Deleterious	0.999	Probably Damaging	0.935	Probably Damaging	3.39	Benign	0.00	Affected			0.0512	0.4643		-3	-2	-0.5	76.10
c.2069C>T	S690F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690F 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 predict a pathogenic outcome: FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). The high‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No predictions are inconclusive or missing. Based on the collective evidence, 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	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-14.325	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	9.85	Destabilizing	2.4	2.17	Destabilizing	6.01	Destabilizing	0.51	Ambiguous	0.384	Likely Benign	-5.76	Deleterious	0.999	Probably Damaging	0.935	Probably Damaging	3.39	Benign	0.00	Affected			0.0498	0.4800		-3	-2	3.6	60.10
c.2111G>A	S704N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704N is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441370‑G‑A). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while premPS and AlphaMissense‑Default are inconclusive. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000					Conflicting		4	6-33441370-G-A	27	1.67e-5	-5.917	Likely Benign	0.421	Ambiguous	Likely Benign	0.48	Likely Benign	0.1	-0.12	Likely Benign	0.18	Likely Benign	0.54	Ambiguous	0.058	Likely Benign	-0.49	Neutral	0.771	Possibly Damaging	0.275	Benign	3.39	Benign	0.08	Tolerated	3.47	10	0.0911	0.3754		1	1	-2.7	27.03	233.2	-29.1	-0.1	0.0	-0.1	0.1						X		Potentially Benign	Ser704 is located at the end and outer surface of an α-helix (res. Thr704-Gly712), which is connected via a tight turn or loop to another α-helix (res. Asp684-Gln702). The hydroxyl side chain of Ser704 occasionally forms a hydrogen bond with the amide group of Ala707. However, in the variant simulations, the carboxamide side chain of Asn704 achieves more lasting and numerous hydrogen-bonding interactions with the residues at the helix end, such as Glu706, Ala707, and Leu708. Consequently, the residue swap could strengthen the α-helix secondary structure integrity at the helix end, which could have either positive or negative effects on its function.
c.2120C>A	A707D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A707D is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools give uncertain results: premPS and Rosetta. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-9.160	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign	0.29	Likely Benign	0.0	-0.61	Ambiguous	-0.16	Likely Benign	0.89	Ambiguous	0.225	Likely Benign	-3.16	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.39	Benign	0.02	Affected			0.1376	0.1741		0	-2	-5.3	44.01
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.2128A>C	K710Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K710Q missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The high‑accuracy AlphaMissense‑Optimized score classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (pathogenic), FATHMM (benign), and PROVEAN (pathogenic)—indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts a benign effect. Overall, the majority of evidence points to a benign impact, and this assessment 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	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-8.920	Likely Pathogenic	0.372	Ambiguous	Likely Benign	0.12	Likely Benign	0.0	0.02	Likely Benign	0.07	Likely Benign	0.49	Likely Benign	0.183	Likely Benign	-3.58	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.39	Benign	0.01	Affected			0.3043	0.1214		1	1	0.4	-0.04
c.2144C>T	P715L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Because the majority of consensus and individual predictors indicate pathogenicity, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for P715L. 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											-12.207	Likely Pathogenic	0.764	Likely Pathogenic	Likely Benign	1.43	Ambiguous	0.1	0.06	Likely Benign	0.75	Ambiguous	0.58	Ambiguous	0.318	Likely Benign	-9.10	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.39	Benign	0.01	Affected			0.1944	0.5105		-3	-3	5.4	16.04
c.2168C>T	T723I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723I is listed in ClinVar as Benign (ClinVar ID 436924.0) and is observed in gnomAD (variant ID 6‑33441633‑C‑T). Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT classifies the change as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates a benign impact. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375					Likely Benign		1	6-33441633-C-T	2	1.24e-6	-2.591	Likely Benign	0.120	Likely Benign	Likely Benign	-0.39	Likely Benign	0.0	-0.20	Likely Benign	-0.30	Likely Benign	0.26	Likely Benign	0.045	Likely Benign	-2.09	Neutral	0.088	Benign	0.030	Benign	3.39	Benign	0.03	Affected	3.50	8	0.0708	0.5803		0	-1	5.2	12.05	252.3	-31.6	0.0	0.0	-0.2	0.2						X		Uncertain	The hydroxyl group of Thr723, located on the outer surface of an α-helix (res. Leu714-Arg726), continuously forms hydrogen bonds with the backbone carbonyl of Asn719 in the WT simulations, potentially lowering the stability of the α-helix. In the variant simulations, the sec-butyl side chain of Ile723 cannot form any hydrogen bonds, which, in theory, could increase the helix stability. However, because the model ends abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2263A>C	M755L 2D AIThe SynGAP1 missense variant M755L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. 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 is benign, and this conclusion does not contradict any ClinVar annotation (none present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.783855	Binding	0.336	0.873	0.375											-1.298	Likely Benign	0.084	Likely Benign	Likely Benign										0.067	Likely Benign	0.03	Neutral	0.000	Benign	0.001	Benign	3.39	Benign	0.22	Tolerated			0.1167	0.3311		4	2	1.9	-18.03
c.2263A>T	M755L 2D AIThe SynGAP1 missense variant M755L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus (majority vote) yields a likely benign classification. Foldetta results are not available, so they do not influence the assessment. Overall, the computational evidence strongly supports a benign interpretation of M755L, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.783855	Binding	0.336	0.873	0.375											-1.298	Likely Benign	0.084	Likely Benign	Likely Benign										0.067	Likely Benign	0.03	Neutral	0.000	Benign	0.001	Benign	3.39	Benign	0.22	Tolerated			0.1167	0.3311		4	2	1.9	-18.03
c.395T>A	F132Y 2D AIThe SynGAP1 missense variant F132Y 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: AlphaMissense‑Optimized is uncertain; 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. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-8.220	Likely Pathogenic	0.839	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-1.98	Neutral	0.272	Benign	0.126	Benign	3.39	Benign	0.00	Affected			0.1635	0.1526		7	3	-4.1	16.00
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.1241T>A	M414K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414K 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 remaining tools—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. FoldX and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is unavailable. Based on the overwhelming agreement among the majority of prediction tools and the high‑accuracy methods, 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	GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-13.537	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.18	Ambiguous	0.1	2.39	Destabilizing	1.79	Ambiguous	1.50	Destabilizing	0.503	Likely Pathogenic	-5.03	Deleterious	0.942	Possibly Damaging	0.860	Possibly Damaging	3.40	Benign	0.04	Affected			0.1299	0.0888		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.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.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.1282T>C	Y428H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y428H is not reported in ClinVar but is present in gnomAD (ID 6‑33438187‑T‑C). 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, AlphaMissense‑Optimized) and the SGM Consensus score (Likely Pathogenic) all suggest a deleterious impact. 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. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation. 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								6-33438187-T-C	1	6.19e-7	-8.566	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	3.18	Destabilizing	0.1	2.20	Destabilizing	2.69	Destabilizing	1.80	Destabilizing	0.458	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.04	Affected	3.38	25	0.2685	0.0711		2	0	-1.9	-26.03
c.1318A>C	N440H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenicity is suggested only by polyPhen‑2 HumDiv and ESM1b, while FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta’s stability prediction is unavailable. 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	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-8.064	Likely Pathogenic	0.226	Likely Benign	Likely Benign	1.12	Ambiguous	0.1	0.83	Ambiguous	0.98	Ambiguous	0.00	Likely Benign	0.140	Likely Benign	-2.48	Neutral	0.835	Possibly Damaging	0.217	Benign	3.40	Benign	0.19	Tolerated			0.0935	0.3270		2	1	0.3	23.04
c.1327G>C	G443R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM all classify it as benign. Only two tools predict pathogenicity: polyPhen‑2 HumDiv and AlphaMissense‑Default. Predictions that are inconclusive—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—are treated as unavailable. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments are: AlphaMissense‑Optimized (uncertain), SGM Consensus (likely benign), and Foldetta (uncertain). Overall, the preponderance of evidence points to a benign impact for G443R, 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 Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-6.954	Likely Benign	0.886	Likely Pathogenic	Ambiguous	-0.88	Ambiguous	0.3	-1.19	Ambiguous	-1.04	Ambiguous	0.28	Likely Benign	0.132	Likely Benign	-1.49	Neutral	0.832	Possibly Damaging	0.286	Benign	3.40	Benign	0.21	Tolerated			0.0934	0.3197		-3	-2	-4.1	99.14
c.1330A>G	K444E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K444E 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 are REVEL and FATHMM; all other evaluated predictors—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic effect. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, 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	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-15.571	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.99	Destabilizing	0.1	3.75	Destabilizing	3.37	Destabilizing	1.10	Destabilizing	0.437	Likely Benign	-3.82	Deleterious	0.997	Probably Damaging	0.981	Probably Damaging	3.40	Benign	0.01	Affected			0.3486	0.0793		0	1	0.4	0.94
c.1333G>C	E445Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445Q is reported in gnomAD (ID 6‑33438238‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b). Two tools remain inconclusive (premPS, AlphaMissense‑Optimized). High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is 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, predicts a benign impact. Overall, the balance of evidence tilts toward pathogenicity, with the high‑accuracy consensus supporting this view, and there is no conflict with 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.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000								6-33438238-G-C	1	6.19e-7	-12.430	Likely Pathogenic	0.790	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	0.20	Likely Benign	0.09	Likely Benign	0.70	Ambiguous	0.240	Likely Benign	-2.86	Deleterious	0.987	Probably Damaging	0.946	Probably Damaging	3.40	Benign	0.12	Tolerated	3.38	31	0.0787	0.5018		2	2	0.0	-0.98
c.1345A>C	S449R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S449R 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 polyPhen‑2 HumVar. Those that predict a pathogenic effect are SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, AlphaMissense‑Default, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifying it as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain stability change. No folding‑stability prediction is definitive. Overall, the majority of tools predict a benign outcome, and this 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.	Likely Pathogenic	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000											-8.486	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	-0.69	Ambiguous	0.2	-1.33	Ambiguous	-1.01	Ambiguous	0.50	Likely Benign	0.145	Likely Benign	-3.36	Deleterious	0.950	Possibly Damaging	0.214	Benign	3.40	Benign	0.18	Tolerated			0.0762	0.3250		0	-1	-3.7	69.11
c.1346G>T	S449I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen2_HumVar. Those that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, and ESM1b. Rosetta and Foldetta 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 (2 benign vs. 2 pathogenic). Foldetta also remains uncertain. Overall, the majority of evidence (7 benign vs. 3 pathogenic) 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	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000											-9.549	Likely Pathogenic	0.310	Likely Benign	Likely Benign	0.04	Likely Benign	0.1	-1.39	Ambiguous	-0.68	Ambiguous	0.13	Likely Benign	0.105	Likely Benign	-3.23	Deleterious	0.559	Possibly Damaging	0.044	Benign	3.40	Benign	0.14	Tolerated			0.0756	0.5006		-1	-2	5.3	26.08
c.1347T>A	S449R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449R 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, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments provide a mixed picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (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 inconclusive result. FoldX and Rosetta predictions are also uncertain and are treated as unavailable. Overall, the evidence is balanced, with an equal number of benign and pathogenic calls, and the high‑accuracy tools do not converge on a single conclusion. Consequently, the variant is most likely pathogenic based on the preponderance of pathogenic 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	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000											-8.486	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	-0.69	Ambiguous	0.2	-1.33	Ambiguous	-1.01	Ambiguous	0.50	Likely Benign	0.168	Likely Benign	-3.36	Deleterious	0.950	Possibly Damaging	0.214	Benign	3.40	Benign	0.18	Tolerated			0.0762	0.3250		0	-1	-3.7	69.11
c.1347T>G	S449R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449R is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar. Those that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicting a benign effect, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta’s stability prediction is uncertain and therefore treated as unavailable. Overall, the predictions are split, with an equal number of benign and pathogenic calls and conflicting high‑accuracy results. Consequently, the variant’s impact remains inconclusive, and there is no contradiction with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000											-8.486	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	-0.69	Ambiguous	0.2	-1.33	Ambiguous	-1.01	Ambiguous	0.50	Likely Benign	0.167	Likely Benign	-3.36	Deleterious	0.950	Possibly Damaging	0.214	Benign	3.40	Benign	0.18	Tolerated			0.0762	0.3250		0	-1	-3.7	69.11
c.1348G>A	A450T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A450T 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 effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools (FoldX, 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. Because the majority of conventional tools lean toward benign and no ClinVar evidence contradicts this, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.321458	Structured	0.306281	Uncertain	0.963	0.234	0.000											-9.149	Likely Pathogenic	0.380	Ambiguous	Likely Benign	0.50	Ambiguous	0.2	0.98	Ambiguous	0.74	Ambiguous	0.81	Ambiguous	0.233	Likely Benign	-3.35	Deleterious	0.996	Probably Damaging	0.973	Probably Damaging	3.40	Benign	0.06	Tolerated			0.0943	0.5902		1	0	-2.5	30.03
c.1348G>C	A450P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A450P missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM Consensus score all classify the change as pathogenic. The high‑accuracy predictors give consistent pathogenic 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 outputs) also predicts pathogenic. premPS remains uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, which is consistent with the absence of a benign ClinVar status. 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											-15.378	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.75	Destabilizing	0.3	8.32	Destabilizing	5.54	Destabilizing	0.72	Ambiguous	0.459	Likely Benign	-4.67	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.40	Benign	0.08	Tolerated			0.1494	0.4309		1	-1	-3.4	26.04
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.1358A>C	H453P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H453P 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. The majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions are missing or inconclusive. Based on the preponderance of evidence, 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	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-15.704	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.29	Destabilizing	0.4	7.04	Destabilizing	5.17	Destabilizing	0.84	Ambiguous	0.488	Likely Benign	-9.88	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.04	Affected			0.2115	0.3938		0	-2	1.6	-40.02
c.1360A>G	I454V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I454V 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, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as likely benign, and Foldetta as uncertain. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.254060	Structured	0.312811	Uncertain	0.965	0.182	0.000											-4.719	Likely Benign	0.657	Likely Pathogenic	Likely Benign	1.47	Ambiguous	0.0	1.36	Ambiguous	1.42	Ambiguous	0.69	Ambiguous	0.132	Likely Benign	-0.79	Neutral	0.935	Possibly Damaging	0.858	Possibly Damaging	3.40	Benign	0.18	Tolerated			0.0833	0.2959		4	3	-0.3	-14.03
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.1373C>A	T458K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T458K 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, Rosetta, SIFT, and FATHMM. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicting pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting benign stability. Overall, the majority of evidence points toward a pathogenic impact, 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	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-13.734	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	-0.59	Ambiguous	0.1	-0.26	Likely Benign	-0.43	Likely Benign	0.80	Ambiguous	0.373	Likely Benign	-5.23	Deleterious	0.999	Probably Damaging	0.973	Probably Damaging	3.40	Benign	0.14	Tolerated			0.1153	0.3326		0	-1	-3.2	27.07
c.1373C>T	T458I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T458I 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. Those that predict a pathogenic impact are SGM‑Consensus (Likely Pathogenic), 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 of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (seven versus six) and the two high‑accuracy pathogenic predictions suggest the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification is available. 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											-9.436	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	-0.40	Likely Benign	0.1	0.29	Likely Benign	-0.06	Likely Benign	0.50	Likely Benign	0.337	Likely Benign	-4.76	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.09	Tolerated			0.0724	0.6128		0	-1	5.2	12.05
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.1384A>C	K462Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K462Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. 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. Overall, the majority of tools and the protein‑stability analysis favor a benign effect, while the consensus pathogenic score introduces uncertainty. Thus, the variant is most likely benign; this assessment does not contradict ClinVar status, which has no entry for K462Q. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.144	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous	0.12	Likely Benign	0.1	0.34	Likely Benign	0.23	Likely Benign	0.48	Likely Benign	0.384	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.15	Tolerated			0.4639	0.1286		1	1	0.4	-0.04
c.1385A>T	K462M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K462M missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, FATHMM, premPS, and the protein‑folding stability method Foldetta; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Rosetta’s output is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also pathogenic, while Foldetta indicates a benign effect on protein stability. No evidence from ClinVar contradicts these findings. Overall, the majority of predictive tools and the consensus score support a pathogenic classification, suggesting that K462M is most likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.837	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	-0.23	Likely Benign	0.1	0.86	Ambiguous	0.32	Likely Benign	0.17	Likely Benign	0.475	Likely Benign	-5.82	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.02	Affected			0.1282	0.3932		0	-1	5.8	3.02
c.1432G>C	E478Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478Q is listed in gnomAD (ID 6‑33438464‑G‑C) but has no ClinVar entry. 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 and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑vs‑2 split. Overall, the majority of evidence (nine benign vs three pathogenic) supports 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.		GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000								6-33438464-G-C	1	6.20e-7	-9.881	Likely Pathogenic	0.603	Likely Pathogenic	Likely Benign	-0.04	Likely Benign	0.0	0.31	Likely Benign	0.14	Likely Benign	0.07	Likely Benign	0.222	Likely Benign	-2.49	Neutral	0.623	Possibly Damaging	0.199	Benign	3.40	Benign	0.14	Tolerated	3.37	34	0.1027	0.5867		2	2	0.0	-0.98
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.1456G>A	E486K 2D 3DClick to see structure in 3D Viewer AISynGAP1 E486K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a benign effect. Because the predictions are split evenly and the high‑accuracy tools are contradictory, the variant’s impact remains uncertain; thus, the variant is most likely pathogenic based on the high‑accuracy predictions, a conclusion that contradicts its ClinVar status of uncertain significance. 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					Uncertain		2				-14.545	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.06	Likely Benign	0.1	0.37	Likely Benign	0.22	Likely Benign	0.41	Likely Benign	0.435	Likely Benign	-3.58	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	3.40	Benign	0.12	Tolerated	3.37	35	0.1940	0.6392		0	1	-0.4	-0.94	206.8	52.1	-0.3	0.1	0.2	0.0	X			X				Uncertain	Glu486 is located in an α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. It is adjacent to the arginine finger (Arg485) and is expected to closely interact with Ras. The residue swap could affect complex formation with the GTPase and its activation. In the WT simulations, the carboxylate group of Glu486 forms salt bridges with Arg485 and Arg475 on the preceding α-helix (res. Ala461-Phe476). In the variant simulations, Lys486 does not form any specific interactions. Although the amino group of the Lys486 side chain cannot form these salt bridges, no negative effects on the protein structure are observed. Nevertheless, the potential role of Glu486 in SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations, and no definite conclusions can be drawn.
c.1501A>T	I501F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I501F missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain (a stability method that integrates FoldX‑MD and Rosetta outputs). No predictions are missing or inconclusive. Overall, the majority of evidence points toward a pathogenic impact, 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	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-12.113	Likely Pathogenic	0.664	Likely Pathogenic	Likely Benign	3.06	Destabilizing	0.1	0.26	Likely Benign	1.66	Ambiguous	0.71	Ambiguous	0.385	Likely Benign	-3.88	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	3.40	Benign	0.03	Affected			0.0574	0.1594		1	0	-1.7	34.02
c.1552T>C	Y518H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are Foldetta, AlphaMissense‑Optimized, and Rosetta. 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 (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y518H, 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	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000					Uncertain		1				-9.797	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	2.39	Destabilizing	0.4	0.82	Ambiguous	1.61	Ambiguous	1.31	Destabilizing	0.496	Likely Benign	-4.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.08	Tolerated			0.1927	0.0212		0	2	-1.9	-26.03
c.1552T>G	Y518D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability 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 (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.247	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	3.92	Destabilizing	0.9	2.68	Destabilizing	3.30	Destabilizing	1.36	Destabilizing	0.619	Likely Pathogenic	-9.41	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.03	Affected			0.3682	0.0212		-4	-3	-2.2	-48.09
c.1563G>C	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E521D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a Benign effect. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1563G>T	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521D missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome. The high‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, 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.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1700A>G	E567G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign impact include REVEL, SIFT, and FATHMM, whereas those that agree on pathogenic impact include AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, Rosetta, and Foldetta. Predictions that are inconclusive are FoldX, 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. Taken together, the majority 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	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-13.402	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous	1.47	Ambiguous	0.0	3.48	Destabilizing	2.48	Destabilizing	0.75	Ambiguous	0.456	Likely Benign	-6.67	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.07	Tolerated			0.2586	0.4715		0	-2	3.1	-72.06
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.1727G>T	C576F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576F 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 limited to FATHMM, which scores the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—consistently predict a pathogenic or likely pathogenic impact. Uncertain predictions from Rosetta and premPS are treated as unavailable. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic; 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 pathogenic. Based on the overwhelming agreement among high‑confidence tools, the variant is most likely pathogenic, 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	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-13.467	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	5.04	Destabilizing	0.5	1.81	Ambiguous	3.43	Destabilizing	0.58	Ambiguous	0.516	Likely Pathogenic	-9.93	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.40	Benign	0.02	Affected			0.1626	0.3527		-4	-2	0.3	44.04
c.1840T>G	Y614D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM predicts it to be benign, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify it as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, 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 prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, 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	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-15.073	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.14	Destabilizing	0.6	4.16	Destabilizing	3.15	Destabilizing	1.69	Destabilizing	0.597	Likely Pathogenic	-9.83	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.02	Affected			0.4013	0.0573		-4	-3	-2.2	-48.09
c.1907T>A	F636Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F636Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a pathogenic outcome (3/4 votes). High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as inconclusive. Stability‑based tools FoldX, Rosetta, and premPS are uncertain. Overall, the majority of evidence points toward 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-9.638	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign	0.84	Ambiguous	0.1	0.51	Ambiguous	0.68	Ambiguous	0.90	Ambiguous	0.394	Likely Benign	-2.89	Deleterious	0.927	Possibly Damaging	0.836	Possibly Damaging	3.40	Benign	0.08	Tolerated			0.1297	0.1866		7	3	-4.1	16.00
c.1907T>G	F636C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636C is reported in gnomAD (ID 6‑33440959‑T‑G) but has no ClinVar entry. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Only FATHMM predicts a benign outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus 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 overwhelming majority of pathogenic predictions, 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	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000								6-33440959-T-G	3	1.86e-6	-13.287	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.1	2.65	Destabilizing	2.20	Destabilizing	1.22	Destabilizing	0.612	Likely Pathogenic	-7.67	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.40	Benign	0.04	Affected	3.37	34	0.2301	0.0830		-2	-4	-0.3	-44.04
c.1914G>C	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, 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. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. 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	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1914G>T	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, 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. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. 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	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1933T>G	F645V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F645V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a pathogenic outcome from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and an uncertain outcome from Foldetta (combining FoldX‑MD and Rosetta). No definitive folding‑stability change is reported. Overall, the majority of evidence points to a pathogenic impact for F645V, and this conclusion does not contradict 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	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-12.175	Likely Pathogenic	0.810	Likely Pathogenic	Ambiguous	1.98	Ambiguous	0.1	1.70	Ambiguous	1.84	Ambiguous	1.02	Destabilizing	0.316	Likely Benign	-4.41	Deleterious	0.036	Benign	0.018	Benign	3.40	Benign	0.02	Affected			0.2163	0.2919		-1	-1	1.4	-48.04
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.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.1947G>A	M649I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M649I has no ClinVar entry 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 (SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; Rosetta is inconclusive and is not counted. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Taken together, the preponderance of evidence supports a pathogenic classification for M649I, and this conclusion does not conflict with ClinVar status, which is currently unavailable. 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											-9.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.42	Destabilizing	0.2	1.96	Ambiguous	2.19	Destabilizing	1.01	Destabilizing	0.449	Likely Benign	-3.99	Deleterious	0.672	Possibly Damaging	0.093	Benign	3.40	Benign	0.02	Affected	3.38	27	0.1215	0.2980		2	1	2.6	-18.03	243.7	21.5	0.0	0.1	0.0	0.1							X	Potentially Benign	The thioether side chain of Met649, located on an α helix (res. Ser641-Glu666), bridges Phe652, Phe648, and Phe639 in an inter-helix hydrophobic cavity in the WT simulations. In the variant simulations, the sec-butyl side chain of Ile649 maintains hydrophobic interactions with nearby residues, with no significant effects on the protein structure.However, methionine is known as a bridging motif for aromatic residues, and these Met-aromatic interactions are lost in the variant. Indeed, in the second variant simulation,the bridging of Phe652, Phe648 and Phe639 is completely lost. In reality, the effect could be more severe on the structure during the protein folding.
c.1947G>C	M649I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649I is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) report a pathogenic outcome; Rosetta is inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Overall, the preponderance of evidence points to a pathogenic effect for M649I, 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	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000					Uncertain		1				-9.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.42	Destabilizing	0.2	1.96	Ambiguous	2.19	Destabilizing	1.01	Destabilizing	0.449	Likely Benign	-3.99	Deleterious	0.672	Possibly Damaging	0.093	Benign	3.40	Benign	0.02	Affected	3.38	27	0.1215	0.2980		2	1	2.6	-18.03	243.7	21.5	0.0	0.1	0.0	0.1							X	Potentially Benign	The thioether side chain of Met649, located on an α helix (res. Ser641-Glu666), bridges Phe652, Phe648, and Phe639 in an inter-helix hydrophobic cavity in the WT simulations. In the variant simulations, the sec-butyl side chain of Ile649 maintains hydrophobic interactions with nearby residues, with no significant effects on the protein structure.However, methionine is known as a bridging motif for aromatic residues, and these Met-aromatic interactions are lost in the variant. Indeed, in the second variant simulation,the bridging of Phe652, Phe648 and Phe639 is completely lost. In reality, the effect could be more severe on the structure during the protein folding.
c.1947G>T	M649I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, votes strongly for pathogenicity (3/4 pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. Rosetta alone is uncertain and is treated as unavailable. Overall, the majority of evidence points to a pathogenic 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	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-9.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.42	Destabilizing	0.2	1.96	Ambiguous	2.19	Destabilizing	1.01	Destabilizing	0.449	Likely Benign	-3.99	Deleterious	0.672	Possibly Damaging	0.093	Benign	3.40	Benign	0.02	Affected	3.38	27	0.1215	0.2980		2	1	2.6	-18.03	243.7	21.5	0.0	0.1	0.0	0.1							X	Potentially Benign	The thioether side chain of Met649, located on an α helix (res. Ser641-Glu666), bridges Phe652, Phe648, and Phe639 in an inter-helix hydrophobic cavity in the WT simulations. In the variant simulations, the sec-butyl side chain of Ile649 maintains hydrophobic interactions with nearby residues, with no significant effects on the protein structure.However, methionine is known as a bridging motif for aromatic residues, and these Met-aromatic interactions are lost in the variant. Indeed, in the second variant simulation,the bridging of Phe652, Phe648 and Phe639 is completely lost. In reality, the effect could be more severe on the structure during the protein folding.
c.1972G>C	G658R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default. Four tools (FoldX, Foldetta, premPS, ESM1b) return uncertain results. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta is uncertain. Because the majority of conventional predictors lean benign and no ClinVar evidence contradicts this, the variant is most likely benign, though the conflicting high‑accuracy predictions leave some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-7.725	In-Between	0.618	Likely Pathogenic	Likely Benign	-1.17	Ambiguous	0.1	-0.46	Likely Benign	-0.82	Ambiguous	0.64	Ambiguous	0.120	Likely Benign	-3.11	Deleterious	0.955	Possibly Damaging	0.591	Possibly Damaging	3.40	Benign	0.19	Tolerated			0.1157	0.3888		-3	-2	-4.1	99.14
c.1985A>C	Q662P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662P 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 are made by SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a consistent pathogenic signal: the SGM‑Consensus score (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. AlphaMissense‑Optimized returns an uncertain result, which is treated as unavailable. Overall, the majority of evidence points to a pathogenic impact for Q662P, and this assessment 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	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-13.174	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	2.15	Destabilizing	0.0	9.37	Destabilizing	5.76	Destabilizing	0.36	Likely Benign	0.268	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.962	Probably Damaging	3.40	Benign	0.08	Tolerated			0.2621	0.4364		0	-1	1.9	-31.01
c.2008C>A	L670M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L670M occurs in the GAP domain. ClinVar contains no entry for this variant, but it is present in gnomAD (ID 6‑33441267‑C‑A). Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, FATHMM, Foldetta, and the SGM‑Consensus score (Likely Benign). Tools that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; Rosetta gives an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000								6-33441267-C-A	2	1.24e-6	-9.438	Likely Pathogenic	0.125	Likely Benign	Likely Benign	-0.11	Likely Benign	0.0	0.70	Ambiguous	0.30	Likely Benign	0.06	Likely Benign	0.038	Likely Benign	-0.16	Neutral	0.970	Probably Damaging	0.777	Possibly Damaging	3.40	Benign	0.25	Tolerated	3.39	27	0.0826	0.3849		2	4	-1.9	18.03
c.2009T>A	L670Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670Q is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, 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 (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also as Likely Benign, while Foldetta remains uncertain. Overall, the majority of available evidence points to a benign impact. 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 Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-8.217	Likely Pathogenic	0.306	Likely Benign	Likely Benign	1.02	Ambiguous	0.1	1.21	Ambiguous	1.12	Ambiguous	0.96	Ambiguous	0.152	Likely Benign	-1.12	Neutral	1.000	Probably Damaging	0.988	Probably Damaging	3.40	Benign	0.36	Tolerated			0.1088	0.1303		-2	-2	-7.3	14.97
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.2015C>A	T672K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T672K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Foldetta, premPS, and Rosetta. 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 majority of tools lean toward a benign interpretation, but the high‑accuracy consensus is split, leaving the variant’s impact uncertain. Thus, the variant is most likely benign based on the bulk of predictions, and this 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	GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000					Uncertain		1				-12.192	Likely Pathogenic	0.698	Likely Pathogenic	Likely Benign	0.20	Likely Benign	0.5	1.21	Ambiguous	0.71	Ambiguous	0.72	Ambiguous	0.065	Likely Benign	-4.31	Deleterious	0.745	Possibly Damaging	0.051	Benign	3.40	Benign	0.07	Tolerated	3.40	25	0.1152	0.3250		0	-1	-3.2	27.07	195.1	7.0	0.4	0.7	0.4	0.1		X				X		Potentially Pathogenic	The hydroxyl group of Thr672, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop itself, such as Lys566, Glu666, and Asn669. In the variant simulations, Lys672 can only form a hydrogen bond with the amino group of the Lys566 side chain via its backbone carbonyl group. Consequently, it cannot maintain the Lys566-Glu666 salt bridge through hydrogen bonding. However, the amino group of Lys periodically forms a salt bridge with the carboxylate group of Glu666, which prevents a drastic disruption of the hydrogen-bond network that keeps the loop close to the helices.
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.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.2045A>T	Y682F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682F 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The SGM Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic votes) and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and the SGM Consensus remains unavailable. Overall, the balance of evidence—both from general predictors and from the high‑accuracy tools—leans toward a benign classification. 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.		GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-9.740	Likely Pathogenic	0.225	Likely Benign	Likely Benign	0.21	Likely Benign	0.1	-0.09	Likely Benign	0.06	Likely Benign	0.42	Likely Benign	0.278	Likely Benign	-3.72	Deleterious	0.997	Probably Damaging	0.947	Probably Damaging	3.40	Benign	0.04	Affected			0.2452	0.3662		7	3	4.1	-16.00
c.2057G>A	G686D 2D AIThe SynGAP1 missense variant G686D 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—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores 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 calculations, also predicts pathogenicity. Based on the collective evidence, 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.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-14.109	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.00	Destabilizing	1.7	2.61	Destabilizing	2.31	Destabilizing	1.05	Destabilizing	0.563	Likely Pathogenic	-6.28	Deleterious	1.000	Probably Damaging	0.967	Probably Damaging	3.40	Benign	0.00	Affected			0.1720	0.2196		1	-1	-3.1	58.04
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.1241T>C	M414T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M414T 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, whereas pathogenic predictions arise from SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta; Rosetta remains uncertain. High‑accuracy methods all support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta predicts a destabilizing, pathogenic outcome. Consequently, the consensus of the most reliable predictors classifies M414T as pathogenic, with no conflict with the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-8.698	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	0.1	1.96	Ambiguous	2.00	Destabilizing	1.27	Destabilizing	0.406	Likely Benign	-5.00	Deleterious	0.997	Probably Damaging	0.972	Probably Damaging	3.41	Benign	0.08	Tolerated			0.1771	0.1976		-1	-1	-2.6	-30.09
c.1255G>C	E419Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. 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 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 predictions are split, with a slight majority leaning toward pathogenicity. The variant is most likely pathogenic based on the current computational 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	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-9.268	Likely Pathogenic	0.923	Likely Pathogenic	Ambiguous	0.01	Likely Benign	0.1	0.36	Likely Benign	0.19	Likely Benign	0.02	Likely Benign	0.280	Likely Benign	-2.80	Deleterious	0.997	Probably Damaging	0.973	Probably Damaging	3.41	Benign	0.04	Affected			0.1499	0.6938		2	2	0.0	-0.98
c.1262C>G	A421G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of tools and the SGM Consensus favor a pathogenic interpretation, while a minority suggest benign. Because there is no ClinVar entry, the predictions do not contradict existing clinical classification. The variant is most likely pathogenic based on the collective computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-9.699	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign	1.47	Ambiguous	0.1	2.13	Destabilizing	1.80	Ambiguous	1.19	Destabilizing	0.137	Likely Benign	-3.59	Deleterious	0.536	Possibly Damaging	0.176	Benign	3.41	Benign	0.05	Affected			0.1692	0.2499		1	0	-2.2	-14.03
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.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.1297G>A	A433T 2D AIThe SynGAP1 A433T missense 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, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the preponderance of evidence, the variant is most likely benign, 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 Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-5.499	Likely Benign	0.080	Likely Benign	Likely Benign	0.35	Likely Benign	0.5	-0.02	Likely Benign	0.17	Likely Benign	0.40	Likely Benign	0.088	Likely Benign	-1.41	Neutral	0.964	Probably Damaging	0.481	Possibly Damaging	3.41	Benign	0.08	Tolerated			0.0891	0.5554		1	0	-2.5	30.03
c.1321G>A	V441I 2D AIThe SynGAP1 missense variant V441I is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while only ESM1b predicts it as pathogenic. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign stability. No contradictory evidence is present. Based on the collective predictions, the variant is most likely benign, and this conclusion 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 Benign	GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-8.773	Likely Pathogenic	0.122	Likely Benign	Likely Benign	-0.24	Likely Benign	0.3	0.11	Likely Benign	-0.07	Likely Benign	0.25	Likely Benign	0.135	Likely Benign	-0.82	Neutral	0.287	Benign	0.038	Benign	3.41	Benign	0.16	Tolerated			0.0694	0.3412		4	3	0.3	14.03
c.1322T>G	V441G 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V441G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; the remaining tools (Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenic, and Foldetta is inconclusive. Taken together, the majority of evidence points to a benign effect, but the SGM Consensus and several individual pathogenic predictors introduce uncertainty. Therefore, the variant is most likely benign based on the overall prediction landscape, 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	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-12.380	Likely Pathogenic	0.478	Ambiguous	Likely Benign	0.18	Likely Benign	0.0	1.25	Ambiguous	0.72	Ambiguous	0.95	Ambiguous	0.273	Likely Benign	-5.88	Deleterious	0.841	Possibly Damaging	0.997	Probably Damaging	3.41	Benign	0.24	Tolerated			0.1664	0.1715		-1	-3	-4.6	-42.08
c.1328G>C	G443A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach a consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. The protein‑folding stability predictor Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and is therefore treated as unavailable evidence. Overall, the collective predictions strongly suggest that the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-0.332	Likely Benign	0.101	Likely Benign	Likely Benign	-0.59	Ambiguous	0.1	-1.61	Ambiguous	-1.10	Ambiguous	-0.52	Ambiguous	0.033	Likely Benign	-1.04	Neutral	0.022	Benign	0.011	Benign	3.41	Benign	0.54	Tolerated			0.3539	0.3192		1	0	2.2	14.03
c.1331A>T	K444M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further highlight the discrepancy: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. Overall, the majority of tools lean toward a pathogenic interpretation, and this is not contradicted by 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	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.223	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.1	-0.47	Likely Benign	-0.04	Likely Benign	0.33	Likely Benign	0.442	Likely Benign	-5.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.41	Benign	0.00	Affected			0.0934	0.3890		0	-1	5.8	3.02
c.1357C>T	H453Y 2D AIThe SynGAP1 missense variant H453Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls come from REVEL, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. Predictions from FoldX, Rosetta, and Foldetta are uncertain. High‑accuracy methods provide a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts likely pathogenic, and Foldetta is inconclusive. Overall, the majority of evidence points toward a pathogenic effect, aligning with the SGM‑Consensus but opposing the benign predictions from several tools. Because ClinVar contains no entry for this variant, there is no conflict with existing clinical annotations. 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											-12.060	Likely Pathogenic	0.753	Likely Pathogenic	Likely Benign	-0.52	Ambiguous	0.7	-0.68	Ambiguous	-0.60	Ambiguous	0.09	Likely Benign	0.320	Likely Benign	-5.93	Deleterious	0.995	Probably Damaging	0.961	Probably Damaging	3.41	Benign	0.04	Affected			0.0815	0.3843		0	2	1.9	26.03
c.1366C>G	Q456E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456E 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, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) yield uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) remaining uncertain. Overall, the predictions are split, but the high‑accuracy consensus leans toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment 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	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-12.982	Likely Pathogenic	0.503	Ambiguous	Likely Benign	0.71	Ambiguous	0.1	0.87	Ambiguous	0.79	Ambiguous	0.65	Ambiguous	0.233	Likely Benign	-2.76	Deleterious	0.998	Probably Damaging	0.964	Probably Damaging	3.41	Benign	0.15	Tolerated			0.1191	0.1276		2	2	0.0	0.98
c.1433A>G	E478G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E478G 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, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. Uncertain predictions come from Rosetta, ESM1b, AlphaMissense‑Default, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to equal benign and pathogenic signals and two uncertain calls; Foldetta likewise yields an uncertain result. Overall, the majority of evaluated tools (seven benign vs. two pathogenic) support a benign classification. This consensus does not contradict any 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	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-7.897	In-Between	0.418	Ambiguous	Likely Benign	0.40	Likely Benign	0.0	0.73	Ambiguous	0.57	Ambiguous	0.02	Likely Benign	0.306	Likely Benign	-4.91	Deleterious	0.923	Possibly Damaging	0.427	Benign	3.41	Benign	0.15	Tolerated			0.2758	0.5572		0	-2	3.1	-72.06
c.1436G>C	R479P 2D 3DClick to see structure in 3D Viewer AIClinVar lists the SynGAP1 R479P variant as Uncertain, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Those that predict a pathogenic effect are FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are AlphaMissense‑Optimized and premPS. 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) as pathogenic. Overall, the majority of tools and the high‑accuracy methods support a pathogenic classification, which is in contrast to the ClinVar designation of uncertain significance. 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					Uncertain		1				-11.795	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	2.86	Destabilizing	0.2	3.88	Destabilizing	3.37	Destabilizing	0.81	Ambiguous	0.277	Likely Benign	-3.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.41	Benign	0.18	Tolerated			0.1993	0.3747		0	-2	2.9	-59.07
c.1442A>T	H481L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H481L 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 REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, 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, the 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 tools (seven benign vs five pathogenic) lean toward a benign interpretation, and this does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign, though a subset of high‑accuracy predictors suggest pathogenicity, indicating some uncertainty. 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											-9.097	Likely Pathogenic	0.587	Likely Pathogenic	Likely Benign	-0.58	Ambiguous	0.1	0.15	Likely Benign	-0.22	Likely Benign	0.29	Likely Benign	0.349	Likely Benign	-5.91	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	3.41	Benign	0.48	Tolerated			0.0661	0.4678		-2	-3	7.0	-23.98
c.1701G>C	E567D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567D 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, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Rosetta, Foldetta, and premPS. 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’s stability prediction is uncertain. Overall, the majority of evidence points toward a pathogenic impact, 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	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-8.276	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.1	1.94	Ambiguous	1.41	Ambiguous	0.70	Ambiguous	0.184	Likely Benign	-2.72	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.21	Tolerated			0.1602	0.3426		3	2	0.0	-14.03
c.1701G>T	E567D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567D missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Rosetta, Foldetta, and premPS. 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’s stability prediction is inconclusive. Overall, the majority of pathogenic predictions outweigh the benign ones, suggesting 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	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-8.276	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.1	1.94	Ambiguous	1.41	Ambiguous	0.70	Ambiguous	0.184	Likely Benign	-2.72	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.21	Tolerated			0.1602	0.3426		3	2	0.0	-14.03
c.1841A>G	Y614C 2D AIThe SynGAP1 missense variant Y614C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods reinforce this view: 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 outputs, also predicts pathogenicity. 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	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-11.716	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.7	3.21	Destabilizing	2.39	Destabilizing	1.76	Destabilizing	0.539	Likely Pathogenic	-8.83	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.41	Benign	0.02	Affected			0.3081	0.1679		0	-2	3.8	-60.04
c.1846G>A	D616N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616N missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into benign (REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b). Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenic, and Foldetta remains uncertain. Overall, the majority of conventional predictors lean toward a benign effect, whereas the SGM Consensus suggests pathogenicity, leaving the variant’s clinical significance ambiguous. Based on the prevailing evidence, 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	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-8.292	Likely Pathogenic	0.349	Ambiguous	Likely Benign	0.54	Ambiguous	0.2	1.05	Ambiguous	0.80	Ambiguous	0.03	Likely Benign	0.149	Likely Benign	-3.74	Deleterious	0.875	Possibly Damaging	0.581	Possibly Damaging	3.41	Benign	0.11	Tolerated			0.1053	0.3976		2	1	0.0	-0.98
c.1907T>C	F636S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636S 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 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) all predict a pathogenic impact. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or folding‑stability result is missing or inconclusive. Based on the overwhelming agreement among the majority of tools and the high‑accuracy methods, 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-14.290	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.08	Destabilizing	0.1	2.66	Destabilizing	2.37	Destabilizing	1.51	Destabilizing	0.559	Likely Pathogenic	-7.50	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.41	Benign	0.03	Affected			0.3877	0.0200		-3	-2	-3.6	-60.10
c.1909T>G	S637A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, SIFT, polyPhen‑2 (HumDiv and HumVar), REVEL, FoldX, and premPS. No tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive (Uncertain). Taken together, the overwhelming majority of evidence indicates a benign effect. The variant’s status 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	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-4.186	Likely Benign	0.137	Likely Benign	Likely Benign	0.31	Likely Benign	0.1	0.99	Ambiguous	0.65	Ambiguous	0.22	Likely Benign	0.078	Likely Benign	-0.64	Neutral	0.120	Benign	0.182	Benign	3.41	Benign	1.00	Tolerated			0.4853	0.2996		1	1	2.6	-16.00
c.1913A>G	K638R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638R is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, PROVEAN and polyPhen‑2 HumDiv predict a pathogenic impact, while premPS remains inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is benign. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000					Uncertain		1				-2.700	Likely Benign	0.110	Likely Benign	Likely Benign	0.09	Likely Benign	0.1	-0.04	Likely Benign	0.03	Likely Benign	0.53	Ambiguous	0.216	Likely Benign	-2.55	Deleterious	0.649	Possibly Damaging	0.240	Benign	3.41	Benign	0.13	Tolerated	3.37	31	0.4026	0.0975		2	3	-0.6	28.01
c.1913A>T	K638M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K638M missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FoldX, FATHMM, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and Rosetta give uncertain results, which are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.702	Likely Pathogenic	0.882	Likely Pathogenic	Ambiguous	-0.21	Likely Benign	0.0	0.61	Ambiguous	0.20	Likely Benign	0.09	Likely Benign	0.526	Likely Pathogenic	-5.19	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.41	Benign	0.01	Affected			0.0929	0.2896		0	-1	5.8	3.02
c.1942T>A	F648I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F648I resides in the GAP domain. ClinVar contains no entry for this change, and it is absent from 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 and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report a pathogenic or likely pathogenic outcome. High‑accuracy assessments reinforce this view: 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) also yields a pathogenic prediction. Taken together, the evidence overwhelmingly supports a pathogenic classification for F648I, 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	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-11.912	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.49	Destabilizing	0.1	2.49	Destabilizing	2.49	Destabilizing	1.05	Destabilizing	0.472	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.04	Affected			0.1673	0.1955		1	0	1.7	-34.02
c.1943T>A	F648Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648Y is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID: 6‑33441202‑T‑A). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. 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 likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic classification for F648Y. 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	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000								6-33441202-T-A	4	2.48e-6	-8.632	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.94	Ambiguous	0.84	Ambiguous	1.11	Destabilizing	0.407	Likely Benign	-2.99	Deleterious	0.984	Probably Damaging	0.913	Probably Damaging	3.41	Benign	0.11	Tolerated	3.37	30	0.1307	0.1396		3	7	-4.1	16.00
c.1968A>C	E656D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656D has no ClinVar entry and is not reported in gnomAD. Prediction tools show mixed results: benign predictions come from REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while pathogenic predictions arise from 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 further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus confirms Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. No evidence from Foldetta or Rosetta is available to refute pathogenicity. Overall, the majority of high‑confidence tools predict a pathogenic impact, and this is consistent with the absence 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	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-11.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	0.275	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			0.2052	0.4120		3	2	0.0	-14.03
c.1968A>T	E656D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E656D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign calls (REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic calls (PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus score is “Likely Pathogenic,” while Foldetta and Rosetta outputs are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, 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	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-11.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	0.273	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			0.2052	0.4120		3	2	0.0	-14.03
c.1975T>A	S659T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign. Only Rosetta reports an uncertain outcome, which is treated as unavailable evidence. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No tool predicts pathogenicity. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-5.693	Likely Benign	0.157	Likely Benign	Likely Benign	-0.15	Likely Benign	0.0	-0.74	Ambiguous	-0.45	Likely Benign	0.42	Likely Benign	0.106	Likely Benign	-2.04	Neutral	0.069	Benign	0.011	Benign	3.41	Benign	0.39	Tolerated			0.1505	0.5976		1	1	0.1	14.03
c.1982A>C	Q661P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from premPS and FATHMM, whereas the remaining 12 tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score) all classify the change as pathogenic or likely pathogenic. 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, which integrates FoldX‑MD and Rosetta stability outputs, also reports a pathogenic effect. No prediction is inconclusive. Consequently, the variant is most likely pathogenic, 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	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-17.549	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	4.11	Destabilizing	0.1	5.97	Destabilizing	5.04	Destabilizing	0.45	Likely Benign	0.531	Likely Pathogenic	-4.58	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.41	Benign	0.01	Affected			0.1811	0.3850		0	-1	1.9	-31.01
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.2009T>C	L670P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. Stability‑based methods are inconclusive: FoldX, Rosetta, and the combined Foldetta output are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-4.916	Likely Benign	0.237	Likely Benign	Likely Benign	0.56	Ambiguous	0.3	1.83	Ambiguous	1.20	Ambiguous	-0.25	Likely Benign	0.211	Likely Benign	2.42	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.41	Benign	0.26	Tolerated			0.3590	0.1474		-3	-3	-5.4	-16.04
c.2033G>C	S678T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678T is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the change as benign: REVEL, FoldX, Rosetta, premPS, 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). No tool predicts pathogenicity. High‑accuracy assessments likewise support a benign effect: AlphaMissense‑Optimized is benign, the SGM Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Based on the unanimous computational evidence, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-5.389	Likely Benign	0.083	Likely Benign	Likely Benign	0.32	Likely Benign	0.1	0.41	Likely Benign	0.37	Likely Benign	0.14	Likely Benign	0.053	Likely Benign	-1.82	Neutral	0.255	Benign	0.053	Benign	3.41	Benign	0.11	Tolerated			0.1494	0.6351		1	1	0.1	14.03
c.2042G>C	G681A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G681A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign calls come from REVEL, polyPhen‑2 HumVar, SIFT, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Predictions labeled uncertain include FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. 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, reports the variant as likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. Overall, the preponderance of evidence points to a pathogenic effect for G681A. 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	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-11.958	Likely Pathogenic	0.836	Likely Pathogenic	Ambiguous	1.77	Ambiguous	1.0	0.89	Ambiguous	1.33	Ambiguous	0.68	Ambiguous	0.354	Likely Benign	-5.99	Deleterious	0.968	Probably Damaging	0.427	Benign	3.41	Benign	0.07	Tolerated			0.3879	0.4401		1	0	2.2	14.03
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.2119G>C	A707P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A707P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, SIFT, and FATHMM, whereas pathogenic predictions come from Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. 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 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.	Likely Pathogenic	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-8.082	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.28	Likely Benign	0.1	5.75	Destabilizing	3.02	Destabilizing	0.76	Ambiguous	0.228	Likely Benign	-2.92	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.41	Benign	0.09	Tolerated			0.1375	0.3095		1	-1	-3.4	26.04
c.2125C>A	L709M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, 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 Benign	GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-5.242	Likely Benign	0.108	Likely Benign	Likely Benign	0.18	Likely Benign	0.0	0.40	Likely Benign	0.29	Likely Benign	-0.10	Likely Benign	0.065	Likely Benign	0.03	Neutral	0.688	Possibly Damaging	0.235	Benign	3.41	Benign	0.17	Tolerated			0.0629	0.2409		4	2	-1.9	18.03
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.2185A>G	N729D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729D is predicted to be benign by all available in‑silico tools. Consensus predictors (REVEL, SIFT, polyPhen‑2 HumDiv/HumVar, PROVEAN, premPS, FoldX, Rosetta, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly report a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign impact on protein stability. ClinVar contains no entry for this variant, and it is not listed in gnomAD. Based on the collective 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		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625											-5.117	Likely Benign	0.270	Likely Benign	Likely Benign	0.03	Likely Benign	0.2	0.10	Likely Benign	0.07	Likely Benign	0.14	Likely Benign	0.054	Likely Benign	-1.22	Neutral	0.390	Benign	0.144	Benign	3.41	Benign	0.55	Tolerated			0.1931	0.2250		2	1	0.0	0.98
c.1246C>G	L416V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for the variant. This conclusion is not contradicted by any ClinVar annotation, as the variant is not present in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-7.861	In-Between	0.310	Likely Benign	Likely Benign	1.46	Ambiguous	0.0	1.78	Ambiguous	1.62	Ambiguous	0.45	Likely Benign	0.124	Likely Benign	-1.47	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.42	Benign	0.53	Tolerated			0.1563	0.3550		2	1	0.4	-14.03
c.1254A>C	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM. 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, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS, 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 indicates that K418N 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	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1254A>T	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions are provided by REVEL and FATHMM, whereas pathogenic predictions are given by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score (Likely Pathogenic). Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain or inconclusive results and are treated as unavailable. 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, and Foldetta’s stability analysis is inconclusive. Overall, the majority of reliable predictors classify K418N as pathogenic, 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	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1273A>G	T425A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Two tools (premPS and AlphaMissense‑Optimized) give uncertain results and are treated as unavailable. High‑accuracy assessments show SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign, and AlphaMissense‑Optimized as uncertain. Overall, the balance of evidence leans toward pathogenicity, 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	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-8.945	Likely Pathogenic	0.799	Likely Pathogenic	Ambiguous	-0.31	Likely Benign	0.1	-0.05	Likely Benign	-0.18	Likely Benign	0.70	Ambiguous	0.372	Likely Benign	-4.17	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.42	Benign	0.09	Tolerated			0.2971	0.2572		1	0	2.5	-30.03
c.1273A>T	T425S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425S 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, Rosetta) 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 tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this assessment 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.		GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-7.420	In-Between	0.676	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.1	0.77	Ambiguous	0.50	Ambiguous	0.63	Ambiguous	0.275	Likely Benign	-3.05	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.42	Benign	0.07	Tolerated			0.2511	0.2324		1	1	-0.1	-14.03
c.1274C>G	T425S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425S 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, Rosetta) 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 tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this assessment 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.		GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-7.420	In-Between	0.676	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.1	0.77	Ambiguous	0.50	Ambiguous	0.63	Ambiguous	0.184	Likely Benign	-3.05	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.42	Benign	0.07	Tolerated			0.2511	0.2324		1	1	-0.1	-14.03
c.1280A>T	H427L 2D 3DClick to see structure in 3D Viewer AISynGAP1 H427L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: nine tools (REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Optimized) predict a benign effect, while five tools (SGM‑Consensus, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. High‑accuracy methods provide a more focused view: AlphaMissense‑Optimized indicates a benign outcome; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, remains pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Taken together, the majority of evidence supports a benign impact for H427L, and this assessment 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	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-9.691	Likely Pathogenic	0.755	Likely Pathogenic	Likely Benign	-0.17	Likely Benign	0.0	0.05	Likely Benign	-0.06	Likely Benign	0.31	Likely Benign	0.272	Likely Benign	-5.38	Deleterious	0.299	Benign	0.033	Benign	3.42	Benign	0.01	Affected			0.0942	0.4953		-2	-3	7.0	-23.98
c.1298C>A	A433E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools (premPS and AlphaMissense‑Default) give uncertain 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 prediction; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports benign. No prediction is missing or inconclusive. Overall, the preponderance of evidence indicates that 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	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-8.210	Likely Pathogenic	0.506	Ambiguous	Likely Benign	-0.20	Likely Benign	0.0	0.15	Likely Benign	-0.03	Likely Benign	0.58	Ambiguous	0.148	Likely Benign	-1.65	Neutral	0.998	Probably Damaging	0.824	Possibly Damaging	3.42	Benign	0.18	Tolerated			0.0783	0.1695		0	-1	-5.3	58.04
c.1346G>C	S449T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449T is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, FoldX, Rosetta, premPS, 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). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus predicts likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on these predictions, the variant is most likely benign, 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 Benign	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000											-6.262	Likely Benign	0.115	Likely Benign	Likely Benign	0.36	Likely Benign	0.1	-0.46	Likely Benign	-0.05	Likely Benign	-0.15	Likely Benign	0.039	Likely Benign	-1.48	Neutral	0.038	Benign	0.008	Benign	3.42	Benign	0.33	Tolerated			0.1219	0.5077		1	1	0.1	14.03
c.1386G>C	K462N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K462N 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 PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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 Pathogenic, and the SGM Consensus also indicates Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result, providing no definitive evidence. Overall, the majority of high‑confidence predictors lean toward pathogenicity, contradicting the absence of a ClinVar classification. 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	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.304	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1386G>T	K462N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462N is reported in gnomAD (ID 6‑33438291‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS) and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K462N. 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	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125								6-33438291-G-T	1	6.20e-7	-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.303	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1433A>C	E478A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E478A 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, 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. No predictions are missing or inconclusive. Overall, the majority of high‑confidence tools lean toward a benign classification, and this does not contradict the lack of ClinVar annotation. 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.	Likely Pathogenic	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-8.499	Likely Pathogenic	0.612	Likely Pathogenic	Likely Benign	0.46	Likely Benign	0.0	0.45	Likely Benign	0.46	Likely Benign	0.02	Likely Benign	0.342	Likely Benign	-4.74	Deleterious	0.585	Possibly Damaging	0.505	Possibly Damaging	3.42	Benign	0.05	Affected			0.3516	0.5847		0	-1	5.3	-58.04
c.1436G>A	R479Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R479Q is listed in ClinVar with an “Uncertain” significance and is present in gnomAD (variant ID 6‑33438468‑G‑A). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv and HumVar both predict a pathogenic impact. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also as likely benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect, and this consensus does not contradict the ClinVar “Uncertain” status; 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.	Likely Benign	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000					Uncertain		1	6-33438468-G-A	7	4.34e-6	-7.109	In-Between	0.259	Likely Benign	Likely Benign	0.54	Ambiguous	0.1	0.57	Ambiguous	0.56	Ambiguous	0.49	Likely Benign	0.191	Likely Benign	-1.16	Neutral	1.000	Probably Damaging	0.991	Probably Damaging	3.42	Benign	0.31	Tolerated	3.39	32	0.2448	0.1812		1	1	1.0	-28.06
c.1677C>G	C559W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change C559W is not listed in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is Uncertain, SGM Consensus is Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Benign. Overall, seven of the twelve evaluated tools predict pathogenicity versus six benign, giving a slight majority toward a deleterious effect. Thus, 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	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-12.765	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	-0.19	Likely Benign	0.0	0.01	Likely Benign	-0.09	Likely Benign	0.44	Likely Benign	0.274	Likely Benign	-8.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.42	Benign	0.03	Affected			0.2492	0.2135		-8	-2	-3.4	83.07
c.1687A>G	R563G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R563G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default all predict deleterious effects, while the consensus SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Benign predictions come from REVEL, SIFT, and FATHMM. High‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a pathogenic outcome from the SGM‑Consensus, and an uncertain outcome from Foldetta (which integrates FoldX‑MD and Rosetta stability scores). 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	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-9.549	Likely Pathogenic	0.848	Likely Pathogenic	Ambiguous	1.41	Ambiguous	0.0	2.01	Destabilizing	1.71	Ambiguous	0.89	Ambiguous	0.253	Likely Benign	-5.68	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.42	Benign	0.13	Tolerated			0.3082	0.1969		-3	-2	4.1	-99.14
c.1687A>T	R563W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R563W 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 (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No evidence from the uncertain tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) supports either outcome. Overall, the balance of evidence favors a pathogenic classification for R563W, 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	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-12.454	Likely Pathogenic	0.854	Likely Pathogenic	Ambiguous	1.25	Ambiguous	0.1	0.79	Ambiguous	1.02	Ambiguous	0.34	Likely Benign	0.302	Likely Benign	-6.75	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.42	Benign	0.01	Affected			0.1378	0.2088		2	-3	3.6	30.03
c.1768A>G	S590G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S590G is listed in ClinVar (ID 1721675.0) with an uncertain significance status and is present in gnomAD (6‑33440820‑A‑G). Functional prediction tools that report a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic majority. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive, as are FoldX, Rosetta, and premPS. Overall, the majority of evidence points toward a pathogenic impact, 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	0.022667	Structured	0.088943	Uncertain	0.918	0.199	0.000					Conflicting		2	6-33440820-A-G	14	8.67e-6	-14.277	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.1	1.28	Ambiguous	0.98	Ambiguous	0.71	Ambiguous	0.379	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.922	Probably Damaging	3.42	Benign	0.06	Tolerated	3.37	35	0.2627	0.4118		1	0	0.4	-30.03	186.7	49.4	0.0	0.0	0.1	0.0		X						Potentially Pathogenic	In the WT simulations, the hydroxyl group of Ser590, located on an α helix (res. Glu582-Met603), forms hydrogen bonds with the backbone carbonyl of Ala634 and/or the carboxamide group of the Asn635 side chain at the end of the opposing α helix (res. Thr619-Ala634).The residue swap could weaken the integrity of the α helix, as glycine is known as an “α helix breaker.” However, no discernible difference was observed between the WT and variant simulations in this regard. Importantly, Gly590 cannot form hydrogen bonds with the opposing helix in the same way that serine can, which could weaken the tertiary structure assembly between the two helices.
c.1772C>A	A591D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591D 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 evaluated algorithms (AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, premPS, FoldX‑MD, Rosetta, Foldetta, and the SGM Consensus) uniformly predict a pathogenic or likely pathogenic outcome; FoldX‑MD is uncertain but does not counter the overall trend. 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) also predicts 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 reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000											-14.747	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.2	2.77	Destabilizing	2.16	Destabilizing	1.40	Destabilizing	0.414	Likely Benign	-5.02	Deleterious	0.919	Possibly Damaging	0.495	Possibly Damaging	3.42	Benign	0.00	Affected			0.1550	0.1741		0	-2	-5.3	44.01
c.1840T>A	Y614N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y614N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas the majority of other in silico predictors (Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; FoldX is inconclusive and is treated as unavailable. 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 (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for Y614N, 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	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-13.004	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.32	Ambiguous	0.5	3.16	Destabilizing	2.24	Destabilizing	1.58	Destabilizing	0.471	Likely Benign	-8.86	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.42	Benign	0.06	Tolerated			0.1944	0.0573		-2	-2	-2.2	-49.07
c.1841A>T	Y614F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614F 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or unavailable results come from Foldetta, premPS, and Rosetta. 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 unavailable. Overall, the majority of reliable predictors indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000											-5.584	Likely Benign	0.630	Likely Pathogenic	Likely Benign	0.09	Likely Benign	0.2	0.98	Ambiguous	0.54	Ambiguous	0.78	Ambiguous	0.364	Likely Benign	-3.75	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.42	Benign	0.07	Tolerated			0.1909	0.2762		7	3	4.1	-16.00
c.1912A>C	K638Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K638Q 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, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default remains uncertain. 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 to a benign 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.		GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.561	Likely Pathogenic	0.556	Ambiguous	Likely Benign	0.45	Likely Benign	0.0	0.37	Likely Benign	0.41	Likely Benign	0.22	Likely Benign	0.421	Likely Benign	-3.60	Deleterious	0.997	Probably Damaging	0.991	Probably Damaging	3.42	Benign	0.12	Tolerated			0.3623	0.0920		1	1	0.4	-0.04
c.1981C>G	Q661E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661E 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Four tools (FoldX, 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 benign, and Foldetta as uncertain. Overall, the majority of available predictions lean toward a benign impact. 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.		GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-12.121	Likely Pathogenic	0.370	Ambiguous	Likely Benign	0.64	Ambiguous	0.1	0.35	Likely Benign	0.50	Ambiguous	0.61	Ambiguous	0.141	Likely Benign	-2.15	Neutral	0.988	Probably Damaging	0.619	Possibly Damaging	3.42	Benign	0.03	Affected			0.1199	0.2439		2	2	0.0	0.98
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.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.1986G>C	Q662H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662H is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools overwhelmingly indicate a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic call comes from polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote) predicts likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. FoldX alone is uncertain, but this does not alter the overall consensus. Based on the collective predictions, the variant is most likely benign, 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 Benign	GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-6.357	Likely Benign	0.331	Likely Benign	Likely Benign	0.53	Ambiguous	0.0	0.18	Likely Benign	0.36	Likely Benign	-0.11	Likely Benign	0.159	Likely Benign	-2.00	Neutral	0.891	Possibly Damaging	0.243	Benign	3.42	Benign	0.15	Tolerated			0.1674	0.3186		3	0	0.3	9.01
c.1986G>T	Q662H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662H is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools overwhelmingly indicate a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while the single pathogenic call comes from polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status, and FoldX is inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the preponderance of evidence, the variant is most likely benign, 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 Benign	GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-6.357	Likely Benign	0.331	Likely Benign	Likely Benign	0.53	Ambiguous	0.0	0.18	Likely Benign	0.36	Likely Benign	-0.11	Likely Benign	0.159	Likely Benign	-2.00	Neutral	0.891	Possibly Damaging	0.243	Benign	3.42	Benign	0.15	Tolerated			0.1674	0.3186		3	0	0.3	9.01
c.2027G>A	S676N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote). Only SIFT predicts a pathogenic outcome. Predictions that are inconclusive (FoldX, premPS, ESM1b) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is unavailable because one component (FoldX) is uncertain. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-7.486	In-Between	0.282	Likely Benign	Likely Benign	0.60	Ambiguous	0.3	-0.21	Likely Benign	0.20	Likely Benign	0.55	Ambiguous	0.099	Likely Benign	-1.63	Neutral	0.438	Benign	0.036	Benign	3.42	Benign	0.05	Affected			0.1454	0.4599		1	1	-2.7	27.03
c.2041G>C	G681R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681R is listed in gnomAD (6-33441300-G-C) but has no ClinVar entry. In silico predictors largely converge on a deleterious effect: benign calls are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report pathogenicity. premPS is inconclusive. High‑accuracy assessments reinforce this trend: 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 pathogenic folding instability. No prediction tool suggests a benign outcome, and the variant’s presence in gnomAD does not alter the consensus. Thus, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000								6-33441300-G-C	1	6.20e-7	-12.170	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.25	Destabilizing	1.7	5.46	Destabilizing	3.86	Destabilizing	0.99	Ambiguous	0.556	Likely Pathogenic	-7.98	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	3.42	Benign	0.00	Affected	3.43	14	0.1022	0.3879		-2	-3	-4.1	99.14
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.2051A>C	D684A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while only premPS and FATHMM predict a benign outcome. High‑accuracy assessments reinforce the pathogenic interpretation: 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 evidence 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	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-14.873	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.34	Destabilizing	1.1	2.85	Destabilizing	3.10	Destabilizing	0.28	Likely Benign	0.547	Likely Pathogenic	-7.98	Deleterious	0.994	Probably Damaging	0.758	Possibly Damaging	3.42	Benign	0.01	Affected			0.3477	0.5423		0	-2	5.3	-44.01
c.2072C>A	T691K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T691K missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, Rosetta, Foldetta, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX returned an uncertain result and is not counted. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus indicates pathogenic. Overall, the majority of tools and the consensus high‑accuracy prediction lean toward pathogenicity. Thus, 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	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-12.104	Likely Pathogenic	0.715	Likely Pathogenic	Likely Benign	-0.50	Ambiguous	0.1	-0.31	Likely Benign	-0.41	Likely Benign	1.27	Destabilizing	0.147	Likely Benign	-3.20	Deleterious	0.937	Possibly Damaging	0.120	Benign	3.42	Benign	0.04	Affected			0.0851	0.2628		0	-1	-3.2	27.07
c.2081C>T	A694V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694V 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are PROVEAN and polyPhen2_HumDiv, while Rosetta and ESM1b give uncertain results. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign; and Foldetta is benign. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-7.099	In-Between	0.221	Likely Benign	Likely Benign	0.46	Likely Benign	0.1	-0.76	Ambiguous	-0.15	Likely Benign	0.24	Likely Benign	0.149	Likely Benign	-2.66	Deleterious	0.970	Probably Damaging	0.207	Benign	3.42	Benign	0.08	Tolerated			0.1238	0.4771		0	0	2.4	28.05
c.2096T>A	V699E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V699E missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign 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 score) indicate a pathogenic effect. 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 Pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, 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	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000											-12.647	Likely Pathogenic	0.813	Likely Pathogenic	Ambiguous	2.41	Destabilizing	0.1	2.08	Destabilizing	2.25	Destabilizing	1.82	Destabilizing	0.468	Likely Benign	-4.56	Deleterious	1.000	Probably Damaging	0.986	Probably Damaging	3.42	Benign	0.02	Affected			0.1092	0.1326		-2	-2	-7.7	29.98
c.2096T>C	V699A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V699A has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while premPS, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar predict a pathogenic impact. Tools with inconclusive results are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is Benign, and the high‑accuracy AlphaMissense‑Optimized also reports Benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is Uncertain. Overall, the majority of evidence points to a benign effect, 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 Benign	GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000											-6.017	Likely Benign	0.426	Ambiguous	Likely Benign	1.37	Ambiguous	0.0	1.30	Ambiguous	1.34	Ambiguous	1.21	Destabilizing	0.236	Likely Benign	-2.39	Neutral	0.861	Possibly Damaging	0.625	Possibly Damaging	3.42	Benign	0.54	Tolerated			0.2450	0.2124		0	0	-2.4	-28.05
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.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.2110A>G	S704G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Taken together, the majority of reliable predictors indicate a benign impact, 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 Benign	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-7.827	In-Between	0.169	Likely Benign	Likely Benign	1.05	Ambiguous	0.1	1.33	Ambiguous	1.19	Ambiguous	0.53	Ambiguous	0.091	Likely Benign	-2.25	Neutral	0.981	Probably Damaging	0.514	Possibly Damaging	3.42	Benign	0.07	Tolerated			0.2224	0.3378		1	0	0.4	-30.03
c.2113A>C	K705Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K705Q missense variant (ClinVar ID 3699560.0) is listed as “Uncertain” in ClinVar and is present in gnomAD (variant ID 6‑33441372‑A‑C). Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (benign), FATHMM (benign), and PROVEAN (benign)—also yields a benign classification; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the preponderance of evidence supports a benign impact for K705Q, and this conclusion does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000					Uncertain		1	6-33441372-A-C	1	6.20e-7	-5.787	Likely Benign	0.436	Ambiguous	Likely Benign	-0.10	Likely Benign	0.0	0.33	Likely Benign	0.12	Likely Benign	-0.02	Likely Benign	0.142	Likely Benign	-0.24	Neutral	0.997	Probably Damaging	0.969	Probably Damaging	3.42	Benign	0.78	Tolerated	3.47	10	0.3063	0.1014		1	1	0.4	-0.04
c.2120C>G	A707G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) give uncertain or inconclusive 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) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of definitive predictions lean toward a benign effect, and there is no ClinVar status to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-7.480	In-Between	0.224	Likely Benign	Likely Benign	1.45	Ambiguous	0.0	1.52	Ambiguous	1.49	Ambiguous	0.62	Ambiguous	0.198	Likely Benign	-2.60	Deleterious	0.991	Probably Damaging	0.960	Probably Damaging	3.42	Benign	0.01	Affected			0.1678	0.2388		1	0	-2.2	-14.03
c.2125C>G	L709V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709V is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool that produced a definitive call classifies the variant as benign: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. The only inconclusive results are FoldX (uncertain) and Foldetta (uncertain), which are treated as unavailable evidence. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also benign; Foldetta remains uncertain. Consequently, the variant is most likely benign, 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 Benign	GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-4.406	Likely Benign	0.101	Likely Benign	Likely Benign	0.75	Ambiguous	0.0	0.42	Likely Benign	0.59	Ambiguous	0.03	Likely Benign	0.063	Likely Benign	-0.36	Neutral	0.062	Benign	0.016	Benign	3.42	Benign	0.45	Tolerated			0.1162	0.2460		2	1	0.4	-14.03
c.2130G>C	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or unavailable results are reported for FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic impact for K710N, 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	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2130G>T	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. In contrast, a majority of algorithms predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, 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 uncertain. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with 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	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2134G>A	G712S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G712S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact comprise FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Uncertain results come from premPS, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive and therefore unavailable. Overall, the majority of evidence points to a pathogenic effect for G712S. This conclusion does not contradict ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000											-7.942	In-Between	0.422	Ambiguous	Likely Benign	2.30	Destabilizing	0.1	4.79	Destabilizing	3.55	Destabilizing	0.62	Ambiguous	0.282	Likely Benign	-4.84	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.02	Affected			0.2862	0.4501		1	0	-0.4	30.03
c.1240A>G	M414V 2D AISynGAP1 M414V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; the remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. The SGM consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic majority. High‑accuracy assessments give AlphaMissense‑Optimized benign, SGM consensus pathogenic, and Foldetta uncertain. Because the high‑accuracy predictions are divided and the overall tool set is evenly split, there is no definitive evidence for pathogenicity or benignity. Thus, the variant is most likely inconclusive, and this lack of consensus does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000					Uncertain		1				-8.003	Likely Pathogenic	0.541	Ambiguous	Likely Benign	1.81	Ambiguous	0.4	1.73	Ambiguous	1.77	Ambiguous	0.95	Ambiguous	0.261	Likely Benign	-2.95	Deleterious	0.999	Probably Damaging	0.987	Probably Damaging	3.43	Benign	0.24	Tolerated			0.2585	0.3482		2	1	2.3	-32.06
c.1261G>A	A421T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421T is not reported in ClinVar and is present in gnomAD (ID 6‑33438166‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of consensus predictions lean toward a benign impact, 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	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000								6-33438166-G-A	1	6.19e-7	-9.217	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.75	Ambiguous	0.2	0.18	Likely Benign	0.47	Likely Benign	0.99	Ambiguous	0.179	Likely Benign	-3.12	Deleterious	0.353	Benign	0.136	Benign	3.43	Benign	0.09	Tolerated	3.37	29	0.1346	0.4439		0	1	-2.5	30.03
c.1285C>G	R429G 2D 3DClick to see structure in 3D Viewer AISynGAP1 R429G 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, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. 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 uncertain. No evidence from FoldX or Rosetta is available. Overall, the predictions are evenly split, with no clear consensus. The variant is most likely of uncertain significance; 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.		GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-9.157	Likely Pathogenic	0.333	Likely Benign	Likely Benign	1.58	Ambiguous	0.0	1.68	Ambiguous	1.63	Ambiguous	1.21	Destabilizing	0.257	Likely Benign	-3.37	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.43	Benign	0.34	Tolerated			0.2888	0.2717		-3	-2	4.1	-99.14
c.1286G>C	R429P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429P 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 effect comprise Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; AlphaMissense‑Default and FoldX 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 (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools and the high‑accuracy methods favor a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. 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											-9.771	Likely Pathogenic	0.556	Ambiguous	Likely Benign	1.53	Ambiguous	0.2	5.13	Destabilizing	3.33	Destabilizing	1.01	Destabilizing	0.265	Likely Benign	-2.89	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.25	Tolerated			0.1881	0.3790		0	-2	2.9	-59.07
c.1296T>G	C432W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432W 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 and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result, providing no counter‑evidence. Overall, the preponderance of evidence from both general and high‑accuracy predictors 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	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-13.936	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.17	Ambiguous	0.4	0.72	Ambiguous	0.95	Ambiguous	0.58	Ambiguous	0.433	Likely Benign	-10.50	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.43	Benign	0.00	Affected			0.1217	0.3246		-8	-2	-3.4	83.07
c.1298C>T	A433V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A433V missense variant is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438203‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, 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 assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore unavailable as evidence. Overall, the majority of predictions support a benign impact, and this is consistent with the lack of ClinVar pathogenic classification. Thus, the variant is most likely benign based on current computational evidence, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000								6-33438203-C-T	240	1.49e-4	-8.200	Likely Pathogenic	0.129	Likely Benign	Likely Benign	0.48	Likely Benign	0.1	-0.07	Likely Benign	0.21	Likely Benign	0.48	Likely Benign	0.096	Likely Benign	-2.91	Deleterious	0.994	Probably Damaging	0.527	Possibly Damaging	3.43	Benign	0.04	Affected	3.37	29	0.0753	0.5104		0	0	2.4	28.05	214.5	-45.8	0.0	0.0	0.0	0.2						X		Potentially Benign	The methyl group of Ala433, located on the outer surface of an α helix (res. Met414-Glu436), does not interact with any nearby residues in the WT simulations. In the variant simulations, the iso-propyl side chain of Val433, which has a similarly hydrophobic profile as alanine, also does not form any lasting interactions at the helix surface. Accordingly, the residue swap does not negatively affect the protein structure based on the simulations.
c.1318A>G	N440D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome, while FoldX, Foldetta, and AlphaMissense‑Default are uncertain. 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 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.		GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-9.335	Likely Pathogenic	0.407	Ambiguous	Likely Benign	-0.62	Ambiguous	0.0	-0.41	Likely Benign	-0.52	Ambiguous	0.47	Likely Benign	0.074	Likely Benign	-1.71	Neutral	0.229	Benign	0.045	Benign	3.43	Benign	0.43	Tolerated			0.1544	0.2025		2	1	0.0	0.98
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.1321G>C	V441L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V441L 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, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome, while Rosetta and AlphaMissense‑Default are uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. No prediction or folding result is missing or inconclusive. Overall, the variant is most likely benign based on the preponderance of evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-9.546	Likely Pathogenic	0.395	Ambiguous	Likely Benign	-0.43	Likely Benign	0.0	0.59	Ambiguous	0.08	Likely Benign	0.45	Likely Benign	0.135	Likely Benign	-2.27	Neutral	0.165	Benign	0.028	Benign	3.43	Benign	0.11	Tolerated			0.0961	0.3881		2	1	-0.4	14.03
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.1330A>C	K444Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K444Q 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 premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, 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 further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K444Q, and this conclusion does not conflict with any ClinVar annotation because none 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											-12.876	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.34	Ambiguous	0.0	1.36	Ambiguous	1.35	Ambiguous	1.04	Destabilizing	0.382	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	3.43	Benign	0.07	Tolerated			0.4112	0.1057		1	1	0.4	-0.04
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.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.1417G>C	V473L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473L 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, and Foldetta, while those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. 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, the majority of tools (seven pathogenic vs. six benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, 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	GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000											-9.073	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	-0.29	Likely Benign	0.1	-0.52	Ambiguous	-0.41	Likely Benign	0.35	Likely Benign	0.336	Likely Benign	-2.85	Deleterious	0.929	Possibly Damaging	0.917	Probably Damaging	3.43	Benign	0.21	Tolerated			0.0708	0.3921		2	1	-0.4	14.03
c.1417G>T	V473L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473L 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, and Foldetta, while those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. 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, the majority of tools (seven pathogenic vs. six benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, 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	GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000											-9.073	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	-0.29	Likely Benign	0.1	-0.52	Ambiguous	-0.41	Likely Benign	0.35	Likely Benign	0.335	Likely Benign	-2.85	Deleterious	0.929	Possibly Damaging	0.917	Probably Damaging	3.43	Benign	0.21	Tolerated			0.0708	0.3921		2	1	-0.4	14.03
c.1435C>G	R479G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R479G is reported in gnomAD (ID 6-33438467-C-G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, Rosetta, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta, which assess protein‑folding stability, returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta as inconclusive. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Therefore, 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	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000								6-33438467-C-G	1	6.20e-7	-8.600	Likely Pathogenic	0.624	Likely Pathogenic	Likely Benign	0.97	Ambiguous	0.0	2.51	Destabilizing	1.74	Ambiguous	0.71	Ambiguous	0.228	Likely Benign	-2.82	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.42	Tolerated	3.39	32	0.2911	0.2707		-2	-3	4.1	-99.14
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.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.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.1524T>A	D508E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D508E is reported in gnomAD (ID 6‑33438556‑T‑A) and has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the protein‑stability method Foldetta. Only PROVEAN predicts a pathogenic outcome, while Rosetta and premPS are inconclusive. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000								6-33438556-T-A	1	6.20e-7	-5.959	Likely Benign	0.242	Likely Benign	Likely Benign	-0.39	Likely Benign	0.1	0.99	Ambiguous	0.30	Likely Benign	0.59	Ambiguous	0.118	Likely Benign	-3.16	Deleterious	0.005	Benign	0.006	Benign	3.43	Benign	0.20	Tolerated	3.37	35	0.1766	0.4304		2	3	0.0	14.03
c.1524T>G	D508E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) all classify the change as benign. Only PROVEAN predicts a pathogenic outcome, while Rosetta and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign stability. Based on the preponderance of evidence, the variant is most likely benign, 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 Benign	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-5.959	Likely Benign	0.242	Likely Benign	Likely Benign	-0.39	Likely Benign	0.1	0.99	Ambiguous	0.30	Likely Benign	0.59	Ambiguous	0.118	Likely Benign	-3.16	Deleterious	0.005	Benign	0.006	Benign	3.43	Benign	0.20	Tolerated	3.37	35	0.1766	0.4304		2	3	0.0	14.03
c.1553A>C	Y518S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518S is not reported in ClinVar and is absent from gnomAD. 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, and AlphaMissense‑Default—consistently 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 is uncertain; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for Y518S, 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	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.453	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous	2.76	Destabilizing	0.8	2.45	Destabilizing	2.61	Destabilizing	1.61	Destabilizing	0.551	Likely Pathogenic	-8.38	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.06	Tolerated			0.3948	0.1059		-3	-2	0.5	-76.10
c.1676G>T	C559F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559F is not reported in ClinVar (ClinVar ID = None) and has no entry in gnomAD (gnomAD ID = None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, 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 predictions are split evenly, but the two most reliable tools (AlphaMissense‑Optimized and Foldetta) both indicate a benign effect, whereas the consensus pathogenic tool is a single outlier. Thus, the variant is most likely benign based on the current computational evidence, 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	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-13.194	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	-0.43	Likely Benign	0.0	-0.04	Likely Benign	-0.24	Likely Benign	0.29	Likely Benign	0.576	Likely Pathogenic	-8.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.43	Benign	0.09	Tolerated			0.2234	0.2653		-4	-2	0.3	44.04
c.1688G>T	R563M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R563M is reported in gnomAD (ID 6‑33440740‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, FATHMM, premPS, and Foldetta; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as benign. No prediction or stability result is missing; all available data are considered. Overall, the balance of evidence leans toward a pathogenic effect, with a single high‑accuracy tool (Foldetta) suggesting benign stability. 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	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000								6-33440740-G-T			-8.910	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	-0.18	Likely Benign	0.1	0.70	Ambiguous	0.26	Likely Benign	0.17	Likely Benign	0.311	Likely Benign	-4.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.43	Benign	0.04	Affected	3.37	35	0.1636	0.2230		-1	0	6.4	-24.99
c.1700A>C	E567A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E567A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Four tools (Foldetta, premPS, Rosetta, AlphaMissense‑Optimized) yield 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. 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	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-12.854	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.1	1.79	Ambiguous	1.11	Ambiguous	0.63	Ambiguous	0.418	Likely Benign	-5.74	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.43	Benign	0.17	Tolerated			0.3170	0.5189		0	-1	5.3	-58.04
c.1921T>G	S641A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641A is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined (REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly classifies the substitution as benign. No pathogenic predictions are present. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign based on current predictions, 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.	Likely Benign	GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000											-6.103	Likely Benign	0.092	Likely Benign	Likely Benign	0.37	Likely Benign	0.2	-0.28	Likely Benign	0.05	Likely Benign	0.27	Likely Benign	0.067	Likely Benign	-2.07	Neutral	0.000	Benign	0.001	Benign	3.43	Benign	0.17	Tolerated			0.4873	0.4680		1	1	2.6	-16.00
c.1930G>C	D644H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D644H 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, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, and AlphaMissense‑Default. 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‑vs‑2 split. No other high‑accuracy predictions are available. 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.		GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-6.786	Likely Benign	0.771	Likely Pathogenic	Likely Benign	0.34	Likely Benign	0.1	-0.83	Ambiguous	-0.25	Likely Benign	0.09	Likely Benign	0.284	Likely Benign	-2.93	Deleterious	0.789	Possibly Damaging	0.158	Benign	3.43	Benign	0.07	Tolerated			0.1656	0.6306		1	-1	0.3	22.05
c.1963C>A	L655M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655M is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the change as benign: REVEL, FoldX, Rosetta, premPS, 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). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM Consensus indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Based on the unanimous benign predictions and the absence of any pathogenic calls, the variant is most likely benign, and this conclusion 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 Benign	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000											-3.077	Likely Benign	0.083	Likely Benign	Likely Benign	0.21	Likely Benign	0.0	0.25	Likely Benign	0.23	Likely Benign	-0.22	Likely Benign	0.076	Likely Benign	0.58	Neutral	0.048	Benign	0.037	Benign	3.43	Benign	0.18	Tolerated			0.0979	0.3252		4	2	-1.9	18.03
c.1971G>C	W657C 2D AISynGAP1 missense variant W657C 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 and FATHMM. Those that predict a deleterious effect are FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta reports an uncertain outcome. High‑accuracy assessments further support a damaging interpretation: 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. Overall, the preponderance of evidence indicates that W657C is most likely pathogenic, which does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000					Uncertain		1				-12.035	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.74	Destabilizing	0.3	1.69	Ambiguous	2.22	Destabilizing	1.30	Destabilizing	0.463	Likely Benign	-11.06	Deleterious	1.000	Probably Damaging	0.982	Probably Damaging	3.43	Benign	0.03	Affected			0.3834	0.0766		-8	-2	3.4	-83.07
c.1971G>T	W657C 2D AIThe SynGAP1 W657C 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 are REVEL and FATHMM, whereas the majority of tools (SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; Foldetta also supports pathogenicity, while Rosetta remains uncertain. High‑accuracy assessments further reinforce a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a pathogenic effect. Overall, the preponderance of 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	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-12.035	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.74	Destabilizing	0.3	1.69	Ambiguous	2.22	Destabilizing	1.30	Destabilizing	0.463	Likely Benign	-11.06	Deleterious	1.000	Probably Damaging	0.982	Probably Damaging	3.43	Benign	0.03	Affected			0.3834	0.0766		-8	-2	3.4	-83.07
c.1998G>C	E666D 2D 3DClick to see structure in 3D Viewer AISynGAP1 E666D is listed in ClinVar with an uncertain significance (ID 587483.0) and is not reported in gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and Rosetta; pathogenic calls come from premPS, PROVEAN, 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 classified as likely pathogenic. High‑accuracy assessments give AlphaMissense‑Optimized a benign prediction, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the balance of evidence slightly favors a pathogenic interpretation, but the predictions are not unequivocal. Thus, the variant is most likely pathogenic according to the current computational data, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000					Uncertain		1				-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.1998G>T	E666D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666D 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, SIFT, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. FoldX alone is also uncertain, so these results are treated as unavailable. Overall, the balance of evidence leans toward a pathogenic impact for E666D, 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	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.2009T>G	L670R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670R 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, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 reliable predictions indicate a benign effect. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.801	Likely Pathogenic	0.552	Ambiguous	Likely Benign	0.64	Ambiguous	0.1	1.42	Ambiguous	1.03	Ambiguous	0.67	Ambiguous	0.193	Likely Benign	-1.74	Neutral	0.993	Probably Damaging	0.755	Possibly Damaging	3.43	Benign	0.41	Tolerated			0.1327	0.1145		-3	-2	-8.3	43.03
c.2014A>T	T672S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T672S is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign or likely benign. No tool predicts pathogenicity. High‑accuracy methods corroborate this: AlphaMissense‑Optimized reports benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Consequently, 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	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000											-4.932	Likely Benign	0.097	Likely Benign	Likely Benign	-0.13	Likely Benign	0.1	0.29	Likely Benign	0.08	Likely Benign	0.61	Ambiguous	0.044	Likely Benign	-2.32	Neutral	0.006	Benign	0.010	Benign	3.43	Benign	0.09	Tolerated			0.3005	0.4282		1	1	-0.1	-14.03
c.2015C>G	T672R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T672R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Foldetta, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results from Rosetta and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus indicates a likely pathogenic outcome. Overall, the majority of individual predictors lean toward pathogenicity, but the high‑accuracy tools provide conflicting benign signals. Therefore, 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	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000											-12.454	Likely Pathogenic	0.626	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.4	1.19	Ambiguous	0.36	Likely Benign	0.60	Ambiguous	0.084	Likely Benign	-4.47	Deleterious	0.886	Possibly Damaging	0.377	Benign	3.43	Benign	0.02	Affected			0.0996	0.2919		-1	-1	-3.8	55.08
c.2032A>G	S678G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678G 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 AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, REVEL, FoldX, premPS, and Foldetta. No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is listed as “Uncertain.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-4.379	Likely Benign	0.069	Likely Benign	Likely Benign	0.24	Likely Benign	0.2	0.55	Ambiguous	0.40	Likely Benign	-0.24	Likely Benign	0.082	Likely Benign	1.90	Neutral	0.000	Benign	0.001	Benign	3.43	Benign	1.00	Tolerated			0.2807	0.4961		1	0	0.4	-30.03
c.2033G>A	S678N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678N is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID 6‑33441292‑G‑A). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Overall, the variant is most likely benign, and this conclusion does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000								6-33441292-G-A	1	6.20e-7	-3.355	Likely Benign	0.139	Likely Benign	Likely Benign	-0.10	Likely Benign	0.1	-0.47	Likely Benign	-0.29	Likely Benign	0.38	Likely Benign	0.067	Likely Benign	-0.63	Neutral	0.001	Benign	0.002	Benign	3.43	Benign	0.14	Tolerated	3.43	19	0.1435	0.4863		1	1	-2.7	27.03
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.2071A>C	T691P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691P is listed in ClinVar (ID 648126.0) as Pathogenic and is not reported in gnomAD. Across the broad panel of in‑silico predictors, three tools (REVEL, SIFT, FATHMM) classify the change as benign, whereas the remaining 11 predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score) report it as pathogenic. High‑accuracy assessments further support a deleterious effect: the AlphaMissense‑Optimized model is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and the Foldetta stability analysis (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence indicates that T691P is most likely pathogenic, which is consistent with its ClinVar classification and does not contradict the database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000					Likely Pathogenic		1				-13.801	Likely Pathogenic	0.905	Likely Pathogenic	Ambiguous	5.04	Destabilizing	0.4	6.09	Destabilizing	5.57	Destabilizing	1.27	Destabilizing	0.214	Likely Benign	-3.43	Deleterious	1.000	Probably Damaging	0.952	Probably Damaging	3.43	Benign	0.06	Tolerated	3.43	14	0.1466	0.4236		0	-1	-0.9	-3.99	188.9	33.0	0.1	0.0	-0.6	0.0	X	X						Potentially Pathogenic	The hydroxyl side chain of Thr691, located in an α-helix (res. Leu696-Leu685), can form hydrogen bonds with the backbone carbonyl and the side chain guanidinium group of Arg687. This interaction facilitates the simultaneous formation of salt bridges between Arg687 and Glu688 on the same α-helix. Additionally, Thr691 occasionally interacts with the thioether side chain of Met409 in an anti-parallel β-sheet of the C2 domain (res. Ile411-Ala399), although this interaction is not consistently maintained throughout the WT simulations. In the variant simulations, the pyrrolidine side chain of Pro691 lacks hydrogen bond donors, making a similar setup impossible. Moreover, proline lacks a free amide group necessary for hydrogen bonding with the carbonyl group of Arg687, introducing a slight bend in the α-helix and compromising its integrity.
c.2105A>G	Q702R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q702R 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, FoldX, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Predictions that remain inconclusive are Rosetta, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to equal benign and pathogenic signals. Overall, the majority of available predictions lean 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.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000					Uncertain		1				-7.894	In-Between	0.348	Ambiguous	Likely Benign	-0.31	Likely Benign	0.1	0.63	Ambiguous	0.16	Likely Benign	0.13	Likely Benign	0.294	Likely Benign	-3.14	Deleterious	0.909	Possibly Damaging	0.889	Possibly Damaging	3.43	Benign	0.02	Affected	3.47	10	0.1225	0.0605		1	1	-1.0	28.06	270.3	-52.9	0.0	0.0	0.0	0.1		X						Potentially Pathogenic	The carboxamide side chain of Gln702 is located at the end and outer surface of an α-helix (res. Leu685-Gln702), where it does not directly form hydrogen bonds with any residues in the WT simulations. In the variant simulations, the positively charged guanidinium group of Arg702 forms a salt bridge with the negatively charged carboxylate group of Glu698 on the same helix and/or hydrogen bonds with the backbone carbonyl group of Ala438 on an opposite α-helix (res. Tyr428-Glu436). Consequently, the residue swap could strengthen the tertiary structure assembly, which could have either positive or negative effects on its function.
c.2119G>T	A707S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A707S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 HumDiv and HumVar classify the variant as pathogenic. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign 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 Benign	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-4.432	Likely Benign	0.113	Likely Benign	Likely Benign	0.70	Ambiguous	0.1	0.63	Ambiguous	0.67	Ambiguous	0.28	Likely Benign	0.150	Likely Benign	-1.07	Neutral	0.848	Possibly Damaging	0.945	Probably Damaging	3.43	Benign	0.08	Tolerated			0.1825	0.2924		1	1	-2.6	16.00
c.2143C>T	P715S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P715S is listed in ClinVar as pathogenic (ClinVar ID 1804065.0) and is present in gnomAD (ID 6‑33441608‑C‑T). Functional prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Predictions that are inconclusive are Rosetta, premPS, ESM1b, 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 majority of evidence points to a pathogenic impact, which is consistent with the ClinVar classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000					Likely Pathogenic		1	6-33441608-C-T	1	6.20e-7	-7.635	In-Between	0.787	Likely Pathogenic	Ambiguous	3.54	Destabilizing	0.0	0.81	Ambiguous	2.18	Destabilizing	0.94	Ambiguous	0.277	Likely Benign	-7.17	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.43	Benign	0.01	Affected	3.50	9	0.2977	0.3755		1	-1	0.8	-10.04	231.8	-14.0	-0.1	0.0	-0.8	0.1							X	Uncertain	Pro715, along with Gly712 and Pro713, are located in a hinge region of an α-helix making a ~90-degree turn (res. Lys705-Leu725). In the WT simulations, the pyrrolidine side chain of Pro715, lacking the backbone amide groups altogether, forces the tight helix turn to take place while also hydrophobically packing with nearby residues (e.g., Leu700, Leu708, Leu714, and Leu718). Leu715, with a normal amide backbone, could potentially affect protein folding and turn formation, although this was not observed in the variant simulations. Additionally, the hydroxyl group of the Ser715 side chain can form hydrogen bonds with the backbone carbonyl group of Gly712 and disrupt the hydrophobic packing arrangement of the leucine residues from the neighboring α-helices, impacting the GAP domain tertiary assembly.
c.2149C>A	L717I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome, while premPS is inconclusive. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Benign. Based on the preponderance of evidence, the variant is most likely benign, 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 Benign	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-4.836	Likely Benign	0.168	Likely Benign	Likely Benign	0.27	Likely Benign	0.0	0.33	Likely Benign	0.30	Likely Benign	-0.73	Ambiguous	0.182	Likely Benign	0.60	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.43	Benign	1.00	Tolerated			0.0712	0.2570		2	2	0.7	0.00
c.2190C>G	I730M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730M 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, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs)—all uniformly indicate a benign impact. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, 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 Benign		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-3.149	Likely Benign	0.110	Likely Benign	Likely Benign	-0.15	Likely Benign	0.1	0.31	Likely Benign	0.08	Likely Benign	-0.15	Likely Benign	0.042	Likely Benign	-0.77	Neutral	0.993	Probably Damaging	0.914	Probably Damaging	3.43	Benign	0.09	Tolerated			0.0698	0.2159		2	1	-2.6	18.03
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.1242G>A	M414I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 M414I 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, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, 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, more tools (five) predict pathogenicity than benign (four), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-6.203	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.0	0.86	Ambiguous	0.85	Ambiguous	0.84	Ambiguous	0.265	Likely Benign	-3.00	Deleterious	0.870	Possibly Damaging	0.801	Possibly Damaging	3.44	Benign	0.36	Tolerated			0.1168	0.3161		2	1	2.6	-18.03
c.1242G>C	M414I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414I 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, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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) is inconclusive (2 vs 2), and Foldetta is uncertain, so these results are treated as unavailable. Overall, the majority of evaluated tools (5 pathogenic vs 4 benign) and the single high‑accuracy pathogenic prediction support a likely pathogenic classification. 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.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-6.203	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.0	0.86	Ambiguous	0.85	Ambiguous	0.84	Ambiguous	0.265	Likely Benign	-3.00	Deleterious	0.870	Possibly Damaging	0.801	Possibly Damaging	3.44	Benign	0.36	Tolerated			0.1168	0.3161		2	1	2.6	-18.03
c.1242G>T	M414I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414I 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, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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) is inconclusive (2 vs 2), and Foldetta is uncertain, so these results are treated as unavailable. Overall, the majority of evaluated tools (5 pathogenic vs 4 benign) and the single high‑accuracy pathogenic prediction support a likely pathogenic classification. 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.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-6.203	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.0	0.86	Ambiguous	0.85	Ambiguous	0.84	Ambiguous	0.265	Likely Benign	-3.00	Deleterious	0.870	Possibly Damaging	0.801	Possibly Damaging	3.44	Benign	0.36	Tolerated			0.1168	0.3161		2	1	2.6	-18.03
c.1262C>A	A421E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic calls are made by ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, Rosetta, premPS, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods give mixed results: FoldX is uncertain, Foldetta is uncertain, and Rosetta alone predicts pathogenic. 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 remains uncertain. Overall, the majority of evidence, including the high‑accuracy tools, points to a pathogenic impact for A421E, 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	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-11.993	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.2	2.07	Destabilizing	1.35	Ambiguous	1.30	Destabilizing	0.233	Likely Benign	-4.24	Deleterious	0.368	Benign	0.144	Benign	3.44	Benign	0.14	Tolerated			0.1288	0.1830		0	-1	-5.3	58.04
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.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.1279C>T	H427Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H427Y 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, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar, as well as the SGM‑Consensus “Likely Benign” call. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and SIFT. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta)—all uniformly indicate a benign effect. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-6.824	Likely Benign	0.328	Likely Benign	Likely Benign	-0.08	Likely Benign	0.0	-0.37	Likely Benign	-0.23	Likely Benign	0.18	Likely Benign	0.180	Likely Benign	-3.47	Deleterious	0.815	Possibly Damaging	0.073	Benign	3.44	Benign	0.01	Affected			0.0958	0.4029		0	2	1.9	26.03
c.1300G>T	V434F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434F is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that indicate a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; SGM‑Consensus predicts pathogenic; Foldetta predicts pathogenic. All predictions are available and none are inconclusive. Based on the overall distribution 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	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-12.553	Likely Pathogenic	0.672	Likely Pathogenic	Likely Benign	3.64	Destabilizing	0.1	3.27	Destabilizing	3.46	Destabilizing	0.27	Likely Benign	0.417	Likely Benign	-3.93	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.44	Benign	0.04	Affected			0.0596	0.3391		-1	-1	-1.4	48.04
c.1310C>A	P437H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the balance of evidence favors a pathogenic classification for P437H, 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	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.496	Likely Pathogenic	0.826	Likely Pathogenic	Ambiguous	1.19	Ambiguous	0.0	-3.28	Stabilizing	-1.05	Ambiguous	0.31	Likely Benign	0.343	Likely Benign	-7.75	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.44	Benign	0.01	Affected			0.1819	0.4328		0	-2	-1.6	40.02
c.1322T>C	V441A 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V441A is listed in ClinVar as uncertain and is present in gnomAD (ID 6‑33438227‑T‑C). Consensus from most in silico predictors favors a benign effect: REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized all report benign. Pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and ESM1b, while premPS and AlphaMissense‑Default remain uncertain. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports benign. Overall, the preponderance of evidence points to a benign impact, aligning with the ClinVar uncertain designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000					Conflicting		2	6-33438227-T-C	3	1.86e-6	-9.439	Likely Pathogenic	0.359	Ambiguous	Likely Benign	-0.14	Likely Benign	0.0	0.33	Likely Benign	0.10	Likely Benign	0.95	Ambiguous	0.053	Likely Benign	-2.92	Deleterious	0.513	Possibly Damaging	0.214	Benign	3.44	Benign	0.93	Tolerated	3.37	29	0.2390	0.1800		0	0	-2.4	-28.05	195.0	44.6	0.0	0.1	0.5	0.0				X		X		Uncertain	The iso-propyl side chain of Val441, located on the outer surface of an α helix (res. Asn440-Thr458), does not interact with other residues in the WT simulations. In the variant simulations, the methyl side chain of Ala441 is similarly hydrophobic and does not form any interactions on the outer helix surface. Although the residue swap does not negatively affect the protein structure based on the simulations, it is noteworthy that the residue faces the RasGTPase interface. Thus, 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.1339G>T	V447F 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V447F 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, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports an uncertain effect on protein folding. Overall, the majority of predictions lean toward pathogenicity, suggesting the variant is most likely pathogenic, a conclusion that does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000					Uncertain		1				-8.673	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	1.40	Ambiguous	0.3	0.61	Ambiguous	1.01	Ambiguous	0.20	Likely Benign	0.206	Likely Benign	-2.62	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.44	Benign	0.03	Affected			0.0551	0.3055		-1	-1	-1.4	48.04
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.1457A>C	E486A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, premPS, SIFT, and FATHMM, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore unavailable. Overall, the majority of evidence supports a pathogenic effect. The prediction aligns 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	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-11.902	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.32	Likely Benign	0.48	Likely Benign	-0.03	Likely Benign	0.398	Likely Benign	-5.17	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.44	Benign	0.39	Tolerated			0.3561	0.5859		0	-1	5.3	-58.04
c.1502T>C	I501T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501T 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, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and premPS, while Rosetta remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of predictions lean toward a benign effect, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000					Uncertain		1				-5.996	Likely Benign	0.252	Likely Benign	Likely Benign	2.40	Destabilizing	0.1	1.81	Ambiguous	2.11	Destabilizing	1.57	Destabilizing	0.362	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.44	Benign	0.16	Tolerated	3.37	35	0.0972	0.0640		0	-1	-5.2	-12.05	214.5	26.9	0.0	0.0	0.5	0.0							X	Potentially Pathogenic	Ile501 is located near a hinge in the middle of an α-helix (res. Leu489-Glu519). The sec-butyl side chain of Ile501 is hydrophobically packed with other residues in the inter-helix space (e.g., Leu500, Tyr497, Phe679) in the WT simulations. In the variant simulations, the hydroxyl group of Thr501 forms a hydrogen bond with the backbone atoms of Tyr497 on the same α-helix, which may weaken the α-helix integrity. Additionally, the polar hydroxyl group of Thr501 is not suitable for the hydrophobic inter-helix space, and thus, the residue swap could affect protein folding. However, Ile501 is followed by Gly502, which facilitates a hinge in the middle of the α-helix, making further weakening caused by Thr501 unlikely to be harmful to the α-helix integrity.
c.1906T>A	F636I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636I 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) reports pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy tools, 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-14.031	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	2.96	Destabilizing	0.2	4.57	Destabilizing	3.77	Destabilizing	1.10	Destabilizing	0.501	Likely Pathogenic	-5.78	Deleterious	0.994	Probably Damaging	0.977	Probably Damaging	3.44	Benign	0.03	Affected			0.1660	0.2153		1	0	1.7	-34.02
c.1906T>G	F636V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636V 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 methods 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 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-14.603	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.1	5.13	Destabilizing	4.10	Destabilizing	1.07	Destabilizing	0.533	Likely Pathogenic	-6.74	Deleterious	0.991	Probably Damaging	0.985	Probably Damaging	3.44	Benign	0.04	Affected			0.1841	0.2030		-1	-1	1.4	-48.04
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.1933T>A	F645I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F645I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are given by premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) report uncertain or inconclusive outcomes. High‑accuracy assessments indicate that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the majority of evaluated predictors (five pathogenic vs four benign) lean toward a pathogenic effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for F645I. 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											-13.055	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	1.12	Ambiguous	0.2	1.68	Ambiguous	1.40	Ambiguous	1.01	Destabilizing	0.299	Likely Benign	-4.24	Deleterious	0.190	Benign	0.019	Benign	3.44	Benign	0.04	Affected			0.1920	0.2891		1	0	1.7	-34.02
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.1939G>T	G647C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647C is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, the majority (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) uniformly predict a benign effect, whereas only SIFT classifies the change as pathogenic. High‑accuracy tools give consistent benign results: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a benign stability change. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-2.955	Likely Benign	0.112	Likely Benign	Likely Benign	0.41	Likely Benign	0.0	-0.20	Likely Benign	0.11	Likely Benign	0.05	Likely Benign	0.112	Likely Benign	-1.63	Neutral	0.003	Benign	0.004	Benign	3.44	Benign	0.02	Affected			0.1194	0.3250		-3	-3	2.9	46.09
c.1960G>A	E654K 2D AIThe SynGAP1 missense variant E654K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, Foldetta predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic. Overall, the majority of high‑confidence predictions lean toward pathogenicity, and the variant is not contradicted by any ClinVar annotation. 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	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-12.587	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.3	0.53	Ambiguous	0.33	Likely Benign	-0.17	Likely Benign	0.435	Likely Benign	-3.80	Deleterious	0.921	Possibly Damaging	0.303	Benign	3.44	Benign	0.11	Tolerated			0.2365	0.4224		0	1	-0.4	-0.94
c.1966G>A	E656K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656K has no ClinVar entry and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” FoldX and Foldetta return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with 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	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-13.833	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-1.06	Ambiguous	0.0	0.02	Likely Benign	-0.52	Ambiguous	0.16	Likely Benign	0.502	Likely Pathogenic	-3.49	Deleterious	0.985	Probably Damaging	0.553	Possibly Damaging	3.44	Benign	0.03	Affected			0.3001	0.6406		0	1	-0.4	-0.94
c.1967A>G	E656G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E656G missense variant has no ClinVar entry and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Only premPS and FATHMM predict a benign outcome, while FoldX and Foldetta are inconclusive. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E656G, and this conclusion is not contradicted by 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	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-14.112	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.1	2.02	Destabilizing	1.49	Ambiguous	0.22	Likely Benign	0.534	Likely Pathogenic	-6.28	Deleterious	1.000	Probably Damaging	0.941	Probably Damaging	3.44	Benign	0.05	Affected			0.3216	0.5208		0	-2	3.1	-72.06
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.2014A>G	T672A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T672A is listed in ClinVar as Benign (ClinVar ID 2154412.0) and is present in gnomAD (variant ID 6‑33441273‑A‑G). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only PROVEAN predicts a pathogenic outcome. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a benign effect, and this conclusion is consistent with the ClinVar designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000					Benign		1	6-33441273-A-G	3	1.86e-6	-6.524	Likely Benign	0.109	Likely Benign	Likely Benign	0.51	Ambiguous	0.3	1.15	Ambiguous	0.83	Ambiguous	0.65	Ambiguous	0.046	Likely Benign	-3.20	Deleterious	0.006	Benign	0.002	Benign	3.44	Benign	0.12	Tolerated	3.40	25	0.3687	0.4380		1	0	2.5	-30.03	188.5	42.5	-0.1	0.3	0.2	0.0		X						Potentially Pathogenic	The hydroxyl group of Thr672, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop itself, such as Lys566, Glu666, and Asn669. In the variant simulations, Ala672 can only form a hydrogen bond with Lys566 via its backbone carbonyl group. Consequently, it cannot maintain the Lys566-Glu666 salt bridge through hydrogen bonding, leading to a significant disruption of the intricate and stable hydrogen-bond network between the loop and the helices.
c.2021C>A	T674N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674N 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, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome; ESM1b is uncertain and does not influence the consensus. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized reports Benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Benign. No contradictory evidence is present. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not conflict with the ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-7.839	In-Between	0.135	Likely Benign	Likely Benign	-0.21	Likely Benign	0.0	0.15	Likely Benign	-0.03	Likely Benign	0.19	Likely Benign	0.119	Likely Benign	-0.71	Neutral	0.958	Probably Damaging	0.671	Possibly Damaging	3.44	Benign	0.17	Tolerated			0.1263	0.4979		0	0	-2.8	13.00
c.2025C>A	N675K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N675K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, and FATHMM, whereas pathogenic calls are made by FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported for Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion 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	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-12.851	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous	2.88	Destabilizing	1.2	0.06	Likely Benign	1.47	Ambiguous	0.74	Ambiguous	0.177	Likely Benign	-4.75	Deleterious	0.993	Probably Damaging	0.688	Possibly Damaging	3.44	Benign	0.02	Affected			0.2424	0.6040		1	0	-0.4	14.07
c.2025C>G	N675K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675K 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 (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Tools with inconclusive results are 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 Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic classification for N675K, 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	GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-12.851	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous	2.88	Destabilizing	1.2	0.06	Likely Benign	1.47	Ambiguous	0.74	Ambiguous	0.177	Likely Benign	-4.75	Deleterious	0.993	Probably Damaging	0.688	Possibly Damaging	3.44	Benign	0.02	Affected			0.2424	0.6040		1	0	-0.4	14.07
c.2032A>C	S678R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678R 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 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, 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) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta predicts a benign effect. Overall, the majority of tools (8 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	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-9.708	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	-0.37	Likely Benign	0.2	0.48	Likely Benign	0.06	Likely Benign	0.32	Likely Benign	0.106	Likely Benign	-2.07	Neutral	0.454	Possibly Damaging	0.057	Benign	3.44	Benign	0.02	Affected			0.0950	0.3519		0	-1	-3.7	69.11
c.2034C>A	S678R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678R 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 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is classified as uncertain. High‑accuracy assessments show AlphaMissense‑Optimized uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta predicts a benign effect. Overall, the majority of evidence (8 benign vs. 4 pathogenic) supports 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.		GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-9.708	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	-0.37	Likely Benign	0.2	0.48	Likely Benign	0.06	Likely Benign	0.32	Likely Benign	0.158	Likely Benign	-2.07	Neutral	0.454	Possibly Damaging	0.057	Benign	3.44	Benign	0.02	Affected			0.0950	0.3519		0	-1	-3.7	69.11
c.2034C>G	S678R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678R 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 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is classified as uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign stability change. Overall, the majority of evidence points to a benign impact. 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.		GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-9.708	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	-0.37	Likely Benign	0.2	0.48	Likely Benign	0.06	Likely Benign	0.32	Likely Benign	0.157	Likely Benign	-2.07	Neutral	0.454	Possibly Damaging	0.057	Benign	3.44	Benign	0.02	Affected			0.0950	0.3519		0	-1	-3.7	69.11
c.2050G>T	D684Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684Y 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: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. Only premPS and FATHMM predict a benign effect. 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 outputs) is 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 the absence of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-15.224	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.65	Destabilizing	1.5	2.12	Destabilizing	2.89	Destabilizing	-0.06	Likely Benign	0.600	Likely Pathogenic	-8.98	Deleterious	1.000	Probably Damaging	0.963	Probably Damaging	3.44	Benign	0.00	Affected			0.0575	0.6564		-4	-3	2.2	48.09
c.2051A>T	D684V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while only premPS and FATHMM predict a benign outcome. High‑accuracy assessments reinforce the pathogenic interpretation: 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 evidence suggests a benign effect, and the lack of ClinVar annotation means there is no conflicting clinical classification. Therefore, 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	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000											-16.128	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.86	Destabilizing	1.1	2.06	Destabilizing	2.96	Destabilizing	0.07	Likely Benign	0.601	Likely Pathogenic	-8.98	Deleterious	0.901	Possibly Damaging	0.480	Possibly Damaging	3.44	Benign	0.00	Affected			0.0775	0.6209		-2	-3	7.7	-15.96
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.2068T>C	S690P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, a conclusion that does not contradict the current ClinVar “Uncertain” classification. 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					Uncertain		1				-14.568	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.84	Destabilizing	0.3	4.40	Destabilizing	4.62	Destabilizing	1.42	Destabilizing	0.431	Likely Benign	-4.77	Deleterious	0.998	Probably Damaging	0.790	Possibly Damaging	3.44	Benign	0.01	Affected	3.42	17	0.1787	0.4050		1	-1	-0.8	10.04	207.5	15.1	0.1	0.0	-0.1	0.2	X	X						Potentially Pathogenic	The hydroxyl side chain of Ser690, located in an α-helix (res. Leu696-Leu685), forms a hydrogen bond with the backbone carbonyl group of Ser410 in an anti-parallel β-sheet of the C2 domain (res. Ile411-Ala399). In the variant simulations, the pyrrolidine side chain of Pro690 cannot form hydrogen bonds with the C2 domain residue, resulting in the loss of this inter-domain connection. Additionally, prolines lack a free amide group necessary for hydrogen bonding with the carbonyl group of Gly686, introducing a slight bend in the α-helix and compromising its integrity.
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.2089T>G	W697G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 W697G missense change 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, SIFT, FATHMM, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic outcome: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar). AlphaMissense‑Default and ESM1b are uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it receives one benign, one pathogenic, and two uncertain calls. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus remains unavailable. Overall, the preponderance of evidence from multiple independent pathogenicity predictors and the protein‑stability assessment by Foldetta indicates that W697G is most likely pathogenic. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-7.429	In-Between	0.480	Ambiguous	Likely Benign	2.57	Destabilizing	0.1	2.38	Destabilizing	2.48	Destabilizing	1.21	Destabilizing	0.485	Likely Benign	-8.93	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.44	Benign	0.06	Tolerated			0.3965	0.1482		-7	-2	0.5	-129.16
c.2101C>A	P701T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P701T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a tolerated change. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports benign. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive, and FoldX alone is uncertain, so these results are treated as unavailable. Overall, the evidence strongly supports a benign effect for P701T, and this assessment 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 Benign	GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000											-6.920	Likely Benign	0.272	Likely Benign	Likely Benign	1.61	Ambiguous	0.0	0.11	Likely Benign	0.86	Ambiguous	-0.18	Likely Benign	0.144	Likely Benign	-0.43	Neutral	0.084	Benign	0.050	Benign	3.44	Benign	0.70	Tolerated			0.1398	0.4160		0	-1	0.9	3.99
c.2129A>G	K710R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K710R 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, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments—all of which are available—show benign predictions: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-6.295	Likely Benign	0.141	Likely Benign	Likely Benign	0.04	Likely Benign	0.0	-0.14	Likely Benign	-0.05	Likely Benign	0.29	Likely Benign	0.209	Likely Benign	-2.78	Deleterious	0.983	Probably Damaging	0.962	Probably Damaging	3.44	Benign	0.02	Affected			0.3351	0.0789		3	2	-0.6	28.01
c.2135G>C	G712A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G712A 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, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Two tools report uncertainty: premPS and AlphaMissense‑Default. High‑accuracy assessments further refine the picture. 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 (2 benign vs. 1 pathogenic vote). Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Because the majority of conventional predictors (7/11) indicate pathogenicity, the overall consensus leans toward a pathogenic impact, despite the mixed high‑accuracy results. 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.		GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000											-6.444	Likely Benign	0.553	Ambiguous	Likely Benign	2.89	Destabilizing	0.1	4.98	Destabilizing	3.94	Destabilizing	0.70	Ambiguous	0.281	Likely Benign	-4.99	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.44	Benign	0.02	Affected			0.3993	0.4105		1	0	2.2	14.03
c.425A>T	K142I 2D AIThe SynGAP1 missense variant K142I 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 Pathogenic, 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 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											-14.597	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.296	Likely Benign	-4.81	Deleterious	0.700	Possibly Damaging	0.403	Benign	3.44	Benign	0.00	Affected			0.1005	0.3173		-2	-3	8.4	-15.01
c.551A>T	E184V 2D AIThe SynGAP1 missense variant E184V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while benign calls are made only by REVEL and FATHMM. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized scores 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 analysis is available for this variant. Overall, the preponderance of evidence indicates that E184V 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		0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-13.119	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.371	Likely Benign	-5.72	Deleterious	0.997	Probably Damaging	0.879	Possibly Damaging	3.44	Benign	0.00	Affected			0.0995	0.8511		-2	-2	7.7	-29.98
c.592C>G	L198V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L198V variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are 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, is labeled Likely Pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (3 pathogenic vs. 1 benign) indicates pathogenicity; Foldetta remains uncertain. Overall, the majority of evaluated tools predict a pathogenic impact, and this is not contradicted by any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic based on current computational predictions. 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											-9.343	Likely Pathogenic	0.747	Likely Pathogenic	Likely Benign	1.10	Ambiguous	0.2	1.24	Ambiguous	1.17	Ambiguous	0.34	Likely Benign	0.265	Likely Benign	-2.54	Deleterious	0.990	Probably Damaging	0.675	Possibly Damaging	3.44	Benign	0.00	Affected			0.1520	0.3017		2	1	0.4	-14.03
c.1268A>T	Y423F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess sequence conservation and functional impact uniformly classify the substitution as benign: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect, while premPS is inconclusive. High‑accuracy methods give consistent benign results: AlphaMissense‑Optimized is benign, the SGM‑Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the overwhelming majority of evidence supports a benign 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 Benign	GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-5.533	Likely Benign	0.181	Likely Benign	Likely Benign	0.03	Likely Benign	0.1	-0.05	Likely Benign	-0.01	Likely Benign	0.76	Ambiguous	0.149	Likely Benign	-2.30	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	3.45	Benign	0.60	Tolerated			0.1934	0.2337		7	3	4.1	-16.00
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.1294T>C	C432R 2D 3DClick to see structure in 3D Viewer AIClinVar has no entry for this SynGAP1 missense variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM. The majority of algorithms predict a pathogenic impact: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). FoldX and Foldetta report uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains inconclusive. Overall, the consensus of the available predictions indicates that 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	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-13.858	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	1.03	Ambiguous	0.2	2.05	Destabilizing	1.54	Ambiguous	1.73	Destabilizing	0.690	Likely Pathogenic	-11.46	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.01	Affected			0.1359	0.1766		-4	-3	-7.0	53.05
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.1295G>A	C432Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C432Y 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, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while benign predictions are reported by REVEL, Rosetta, FATHMM, and Foldetta. Tools with uncertain or missing results (FoldX, premPS) are not considered evidence. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predict pathogenicity, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of predictions support a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none available). 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											-13.720	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.62	Ambiguous	0.3	0.31	Likely Benign	0.47	Likely Benign	0.71	Ambiguous	0.441	Likely Benign	-10.50	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.02	Affected			0.0857	0.3438		0	-2	-3.8	60.04
c.1309C>A	P437T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P437T 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, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools—FoldX, 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 yielding an uncertain stability change. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. 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.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.011	Likely Pathogenic	0.484	Ambiguous	Likely Benign	1.35	Ambiguous	0.0	-3.46	Stabilizing	-1.06	Ambiguous	0.54	Ambiguous	0.305	Likely Benign	-6.67	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.45	Benign	0.01	Affected			0.1659	0.5782		0	-1	0.9	3.99
c.1331A>C	K444T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444T 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. Those that predict a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Foldetta, Rosetta, 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 uncertain (treated as unavailable for pathogenicity inference). Overall, the majority of reliable predictions indicate 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	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-15.557	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.1	1.17	Ambiguous	1.65	Ambiguous	0.96	Ambiguous	0.442	Likely Benign	-5.73	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.01	Affected			0.1643	0.3416		0	-1	3.2	-27.07
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.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.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.1553A>G	Y518C 2D AIThe SynGAP1 missense variant Y518C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; and uncertain results from Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta predicts pathogenic folding instability. Overall, the majority of evidence points to 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	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-9.813	Likely Pathogenic	0.794	Likely Pathogenic	Ambiguous	2.99	Destabilizing	0.9	1.70	Ambiguous	2.35	Destabilizing	0.69	Ambiguous	0.415	Likely Benign	-8.35	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.16	Tolerated			0.2905	0.1128		0	-2	3.8	-60.04
c.1676G>A	C559Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C559Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. 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 evidence is split evenly between benign and pathogenic predictions and the high‑accuracy tools disagree, the variant is best classified as of uncertain significance. This assessment does not contradict ClinVar status, as no ClinVar entry exists. 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											-11.767	Likely Pathogenic	0.868	Likely Pathogenic	Ambiguous	-0.37	Likely Benign	0.0	-0.19	Likely Benign	-0.28	Likely Benign	0.36	Likely Benign	0.561	Likely Pathogenic	-8.39	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.45	Benign	0.10	Tolerated			0.2094	0.2135		0	-2	-3.8	60.04
c.1699G>A	E567K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E567K is not reported in ClinVar (no entry) and is absent from gnomAD. Prediction tools cluster into two groups: benign calls come from REVEL, FoldX, SIFT, and FATHMM, while pathogenic calls arise from Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (likely pathogenic). High‑accuracy methods reinforce the pathogenic assessment: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains uncertain. PremPS is likewise inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar status or gnomAD presence. 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											-15.568	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	-0.18	Likely Benign	0.0	2.61	Destabilizing	1.22	Ambiguous	0.65	Ambiguous	0.380	Likely Benign	-3.75	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	3.45	Benign	0.16	Tolerated			0.2115	0.5552		0	1	-0.4	-0.94
c.1909T>A	S637T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-4.116	Likely Benign	0.092	Likely Benign	Likely Benign	0.36	Likely Benign	0.1	-0.91	Ambiguous	-0.28	Likely Benign	-0.39	Likely Benign	0.067	Likely Benign	-0.19	Neutral	0.086	Benign	0.019	Benign	3.45	Benign	0.19	Tolerated			0.1675	0.4572		1	1	0.1	14.03
c.1919C>A	T640N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. Only the protein‑stability predictors FoldX and Rosetta returned uncertain results, which are treated as unavailable evidence. High‑accuracy assessments corroborate the benign prediction: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also reports a benign effect. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-4.258	Likely Benign	0.107	Likely Benign	Likely Benign	-0.50	Ambiguous	0.2	0.53	Ambiguous	0.02	Likely Benign	0.03	Likely Benign	0.097	Likely Benign	0.51	Neutral	0.229	Benign	0.084	Benign	3.45	Benign	0.25	Tolerated			0.1518	0.4079		0	0	-2.8	13.00
c.1930G>A	D644N 2D AIThe SynGAP1 missense variant D644N 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, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all classifying the substitution as benign. No tool predicts pathogenicity. The only inconclusive result is AlphaMissense‑Default, which is listed as uncertain and therefore does not influence the overall assessment. High‑accuracy methods further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-4.389	Likely Benign	0.360	Ambiguous	Likely Benign	0.06	Likely Benign	0.3	-0.28	Likely Benign	-0.11	Likely Benign	0.02	Likely Benign	0.124	Likely Benign	-2.28	Neutral	0.007	Benign	0.001	Benign	3.45	Benign	0.25	Tolerated			0.1368	0.6261		2	1	0.0	-0.98
c.1940G>A	G647D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G647D is reported in ClinVar as having no entry and is present in gnomAD (6‑33441199‑G‑A). Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized all predict benign. Only AlphaMissense‑Default predicts pathogenic, while FoldX, Foldetta, premPS, and ESM1b are uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields benign; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the consensus of most tools and the high‑accuracy predictions indicate that G647D is most likely benign, and this is consistent with the absence of a pathogenic ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000								6-33441199-G-A	1	6.20e-7	-7.643	In-Between	0.582	Likely Pathogenic	Likely Benign	0.68	Ambiguous	0.1	0.33	Likely Benign	0.51	Ambiguous	0.56	Ambiguous	0.098	Likely Benign	-1.63	Neutral	0.282	Benign	0.128	Benign	3.45	Benign	0.24	Tolerated	3.37	30	0.1630	0.1372		-1	1	-3.1	58.04
c.1942T>C	F648L 2D AISynGAP1 missense variant F648L is listed in ClinVar with an uncertain significance (ClinVar ID 3383902.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b—consistently predict pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores 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 F648L, which contradicts the current ClinVar uncertain status. 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					Uncertain		1				-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	0.468	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			0.1961	0.3126		2	0	1.0	-34.02
c.1944C>A	F648L 2D AIThe SynGAP1 missense variant F648L 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, SIFT, and FATHMM, while the remaining 12 tools—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic; and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic. Because the majority of evidence points to a deleterious impact and there is 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	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	0.319	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			0.1961	0.3126		2	0	1.0	-34.02
c.1944C>G	F648L 2D AIThe SynGAP1 missense variant F648L 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, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b all indicate pathogenicity, and the SGM Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: 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. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation. 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											-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	0.319	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			0.1961	0.3126		2	0	1.0	-34.02
c.1963C>G	L655V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. No tools predict pathogenicity, and the uncertain stability assessment does not alter the overall benign inference. Therefore, based on the available predictions, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000											-6.743	Likely Benign	0.127	Likely Benign	Likely Benign	0.78	Ambiguous	0.0	0.58	Ambiguous	0.68	Ambiguous	0.38	Likely Benign	0.058	Likely Benign	-0.62	Neutral	0.008	Benign	0.003	Benign	3.45	Benign	0.44	Tolerated			0.1551	0.3190		2	1	0.4	-14.03
c.1993T>C	Y665H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665H is not reported in ClinVar (ClinVar status: not reported) but is present in gnomAD (gnomAD ID: 6‑33441252‑T‑C). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain. Overall, the majority of predictions (7 benign vs. 4 pathogenic) and the high‑accuracy consensus support a benign classification. 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	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000								6-33441252-T-C	2	1.24e-6	-9.303	Likely Pathogenic	0.389	Ambiguous	Likely Benign	0.85	Ambiguous	0.0	0.28	Likely Benign	0.57	Ambiguous	1.12	Destabilizing	0.129	Likely Benign	-2.00	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.45	Benign	0.48	Tolerated	3.38	28	0.2122	0.0513		2	0	-1.9	-26.03
c.1994A>G	Y665C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665C is listed in ClinVar with no assertion (status: None) and is present in gnomAD (ID 6‑33441253‑A‑G). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 evidence is mixed, but the majority of high‑confidence tools lean toward a benign interpretation. Thus, the variant is most likely benign based on current predictions, and this does not contradict the ClinVar status, which remains unclassified. 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								6-33441253-A-G	1	6.20e-7	-9.007	Likely Pathogenic	0.261	Likely Benign	Likely Benign	1.05	Ambiguous	0.1	1.60	Ambiguous	1.33	Ambiguous	1.12	Destabilizing	0.210	Likely Benign	-3.22	Deleterious	1.000	Probably Damaging	0.981	Probably Damaging	3.45	Benign	0.14	Tolerated	3.38	28	0.2562	0.2019		-2	0	3.8	-60.04
c.1994A>T	Y665F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, 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, while Rosetta and Foldetta are uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” status. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar claim; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-8.460	Likely Pathogenic	0.100	Likely Benign	Likely Benign	0.07	Likely Benign	0.1	1.03	Ambiguous	0.55	Ambiguous	0.38	Likely Benign	0.106	Likely Benign	-1.23	Neutral	0.159	Benign	0.036	Benign	3.45	Benign	0.47	Tolerated			0.2277	0.3076		7	3	4.1	-16.00
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.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.2020A>G	T674A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly favor a benign effect: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, REVEL, FoldX, premPS, Foldetta, and the SGM‑Consensus score all indicate benign or likely benign. No tool predicts pathogenicity; the only inconclusive result comes from Rosetta, which is listed as uncertain. High‑accuracy methods corroborate the benign assessment: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the aggregate predictions, 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.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-5.915	Likely Benign	0.099	Likely Benign	Likely Benign	-0.13	Likely Benign	0.0	0.89	Ambiguous	0.38	Likely Benign	0.29	Likely Benign	0.052	Likely Benign	-1.48	Neutral	0.398	Benign	0.045	Benign	3.45	Benign	0.28	Tolerated			0.4042	0.4845		1	0	2.5	-30.03
c.2033G>T	S678I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678I 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, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, 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 majority of evidence (10 benign vs. 3 pathogenic) supports a benign classification. This consensus 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	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-9.735	Likely Pathogenic	0.253	Likely Benign	Likely Benign	0.36	Likely Benign	0.3	-0.01	Likely Benign	0.18	Likely Benign	-0.11	Likely Benign	0.119	Likely Benign	-3.99	Deleterious	0.294	Benign	0.057	Benign	3.45	Benign	0.01	Affected			0.0941	0.5954		-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.2042G>A	G681D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681D 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 the remaining 11 tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all predict pathogenicity. The high‑accuracy methods reinforce this view: AlphaMissense‑Optimized returns a pathogenic classification; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. premPS is inconclusive and is treated as unavailable. Taken together, the overwhelming majority of evidence points to a pathogenic impact for G681D. 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	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-12.451	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	2.62	Destabilizing	1.5	4.54	Destabilizing	3.58	Destabilizing	0.96	Ambiguous	0.471	Likely Benign	-6.98	Deleterious	0.999	Probably Damaging	0.840	Possibly Damaging	3.45	Benign	0.00	Affected			0.1697	0.1695		1	-1	-3.1	58.04
c.2068T>G	S690A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta reports an uncertain stability change, so these results are treated as unavailable. Overall, the balance of evidence favors 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.		GAP	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-8.763	Likely Pathogenic	0.318	Likely Benign	Likely Benign	-0.82	Ambiguous	0.0	-2.17	Stabilizing	-1.50	Ambiguous	0.45	Likely Benign	0.217	Likely Benign	-2.55	Deleterious	0.887	Possibly Damaging	0.738	Possibly Damaging	3.45	Benign	0.21	Tolerated			0.4619	0.3131		1	1	2.6	-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.2106G>C	Q702H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702H 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, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain results come from FoldX and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign outcome (2 benign vs. 1 pathogenic vote), and Foldetta predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely benign, 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	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-7.966	In-Between	0.211	Likely Benign	Likely Benign	0.55	Ambiguous	0.0	0.13	Likely Benign	0.34	Likely Benign	0.12	Likely Benign	0.233	Likely Benign	-4.11	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.45	Benign	0.00	Affected			0.0811	0.2555		3	0	0.3	9.01
c.2106G>T	Q702H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702H 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, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain results come from FoldX and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign outcome (2 benign vs. 1 pathogenic vote), and Foldetta predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely benign, 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	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-7.966	In-Between	0.211	Likely Benign	Likely Benign	0.55	Ambiguous	0.0	0.13	Likely Benign	0.34	Likely Benign	0.12	Likely Benign	0.233	Likely Benign	-4.11	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.45	Benign	0.00	Affected			0.0811	0.2555		3	0	0.3	9.01
c.2111G>C	S704T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704T is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. Only polyPhen‑2 HumDiv predicts a pathogenic effect, while FoldX remains inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the aggregate evidence indicates that S704T is most likely benign, 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 Benign	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000					Uncertain		1				-4.930	Likely Benign	0.265	Likely Benign	Likely Benign	0.80	Ambiguous	0.0	0.15	Likely Benign	0.48	Likely Benign	0.29	Likely Benign	0.071	Likely Benign	-1.72	Neutral	0.525	Possibly Damaging	0.107	Benign	3.45	Benign	0.07	Tolerated	3.47	10	0.1036	0.4674		1	1	0.1	14.03	201.7	-18.0	0.0	0.0	-0.2	0.7						X		Potentially Benign	Ser704 is located at the end and outer surface of an α-helix (res. Thr704-Gly712), which is connected via a tight turn or loop to another α-helix (res. Asp684-Gln702). The hydroxyl side chain of Ser704 occasionally forms a hydrogen bond with the amide group of Ala707. Similarly, in the variant simulations, the hydroxyl side chain of Thr704 forms hydrogen bonds with the amide groups of Ala707 and Leu708. Thus, the residue swap does not cause any apparent structural change.
c.2120C>T	A707V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707V variant is not reported in ClinVar (no ClinVar ID) but is present in gnomAD (variant ID 6‑33441585‑C‑T). Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign classification. Only three tools—Rosetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar—predict pathogenicity, while Foldetta reports an uncertain stability change. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta remains uncertain. Overall, the majority of evidence supports a benign impact for A707V, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000								6-33441585-C-T	1	6.20e-7	-6.479	Likely Benign	0.277	Likely Benign	Likely Benign	0.05	Likely Benign	0.0	2.17	Destabilizing	1.11	Ambiguous	-0.30	Likely Benign	0.212	Likely Benign	-1.62	Neutral	0.991	Probably Damaging	0.912	Probably Damaging	3.45	Benign	1.00	Tolerated	3.50	9	0.0794	0.4048		0	0	2.4	28.05
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.2143C>G	P715A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P715A has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by FoldX, 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, is classified as Likely Pathogenic. High‑accuracy assessments further indicate AlphaMissense‑Optimized predicts Benign, whereas the SGM‑Consensus remains Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is Uncertain. Overall, the majority of evidence points toward a pathogenic effect, 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	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-9.261	Likely Pathogenic	0.597	Likely Pathogenic	Likely Benign	2.69	Destabilizing	0.0	0.28	Likely Benign	1.49	Ambiguous	0.77	Ambiguous	0.229	Likely Benign	-7.13	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.45	Benign	0.02	Affected			0.2993	0.3560		1	-1	3.4	-26.04
c.2188A>T	I730F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730F has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or tolerated. Only polyPhen2_HumDiv classifies the change as pathogenic. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, reports a benign effect. No prediction tool or stability analysis is inconclusive. Based on the collective evidence, the variant is most likely benign, 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 Benign		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-4.953	Likely Benign	0.173	Likely Benign	Likely Benign	-0.54	Ambiguous	0.1	-0.01	Likely Benign	-0.28	Likely Benign	-0.01	Likely Benign	0.055	Likely Benign	-1.86	Neutral	0.699	Possibly Damaging	0.152	Benign	3.45	Benign	0.08	Tolerated			0.0509	0.2082		1	0	-1.7	34.02
c.3991A>C	I1331L 2D AIThe SynGAP1 missense variant I1331L 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, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with 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 Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-2.450	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-1.04	Neutral	0.762	Possibly Damaging	0.785	Possibly Damaging	3.45	Benign	0.00	Affected			0.0752	0.3616		2	2	-0.7	0.00
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.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.1261G>T	A421S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A421S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from PROVEAN, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus predicts pathogenic, and 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 tools lean toward a pathogenic interpretation, and this aligns with the SGM‑Consensus result; there is no conflict with 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	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-9.220	Likely Pathogenic	0.715	Likely Pathogenic	Likely Benign	0.66	Ambiguous	0.1	1.12	Ambiguous	0.89	Ambiguous	0.70	Ambiguous	0.155	Likely Benign	-2.50	Deleterious	0.058	Benign	0.072	Benign	3.46	Benign	0.08	Tolerated			0.2247	0.3621		1	1	-2.6	16.00
c.1295G>T	C432F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432F 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 lack of ClinVar annotation. 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											-12.862	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	-0.44	Likely Benign	0.2	-0.34	Likely Benign	-0.39	Likely Benign	0.57	Ambiguous	0.434	Likely Benign	-10.50	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.01	Affected			0.1090	0.3956		-4	-2	0.3	44.04
c.1297G>T	A433S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or likely benign. Only polyPhen‑2 (HumDiv) predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely benign classification; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence points to a benign impact for A433S, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-3.861	Likely Benign	0.077	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	0.41	Likely Benign	0.19	Likely Benign	-0.21	Likely Benign	0.077	Likely Benign	0.35	Neutral	0.597	Possibly Damaging	0.391	Benign	3.46	Benign	0.28	Tolerated			0.1938	0.3975		1	1	-2.6	16.00
c.1325A>G	K442R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K442R is catalogued in gnomAD (ID 6‑33438230‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tools predicting a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000								6-33438230-A-G	1	6.20e-7	-5.761	Likely Benign	0.093	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.29	Likely Benign	0.21	Likely Benign	0.51	Ambiguous	0.098	Likely Benign	-1.42	Neutral	0.972	Probably Damaging	0.875	Possibly Damaging	3.46	Benign	0.35	Tolerated	3.37	29	0.3885	0.0778		2	3	-0.6	28.01
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.1379A>G	K460R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K460R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity, while Rosetta and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Taken together, the overwhelming majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-5.349	Likely Benign	0.175	Likely Benign	Likely Benign	-0.41	Likely Benign	0.0	0.63	Ambiguous	0.11	Likely Benign	0.55	Ambiguous	0.103	Likely Benign	-1.52	Neutral	0.991	Probably Damaging	0.962	Probably Damaging	3.46	Benign	0.63	Tolerated			0.5093	0.1169	Weaken	3	2	-0.6	28.01
c.1427T>A	F476Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, 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 Foldetta predicts a benign outcome. Overall, the balance of evidence leans toward a benign impact for F476Y, 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	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-9.707	Likely Pathogenic	0.576	Likely Pathogenic	Likely Benign	0.50	Ambiguous	0.2	0.30	Likely Benign	0.40	Likely Benign	1.10	Destabilizing	0.169	Likely Benign	-1.10	Neutral	0.965	Probably Damaging	0.919	Probably Damaging	3.46	Benign	0.90	Tolerated			0.1109	0.1568		7	3	-4.1	16.00
c.1427T>G	F476C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476C is catalogued in gnomAD (ID 6‑33438459‑T‑G) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. 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, seven tools predict pathogenicity versus six predicting benign, with no ClinVar evidence to contradict this assessment. Thus, the variant is most likely pathogenic based on the current computational predictions. 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								6-33438459-T-G			-9.270	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	2.05	Destabilizing	0.1	2.62	Destabilizing	2.34	Destabilizing	-0.30	Likely Benign	0.280	Likely Benign	2.69	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	3.46	Benign	0.83	Tolerated	3.40	22	0.2051	0.1251		-2	-4	-0.3	-44.04
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.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.1919C>T	T640I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640I 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, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only PROVEAN predicts a pathogenic outcome. The remaining tools (FoldX, Rosetta, ESM1b, AlphaMissense‑Default, and Foldetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is unavailable due to a tie, and Foldetta also yields an uncertain stability change. Overall, the majority of evidence points to a benign effect, and this conclusion 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.		GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-7.256	In-Between	0.358	Ambiguous	Likely Benign	0.70	Ambiguous	0.1	0.66	Ambiguous	0.68	Ambiguous	0.28	Likely Benign	0.193	Likely Benign	-2.75	Deleterious	0.322	Benign	0.022	Benign	3.46	Benign	0.12	Tolerated			0.1030	0.4793		0	-1	5.2	12.05
c.1931A>G	D644G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D644G 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and AlphaMissense‑Default (polyPhen‑2 HumVar is benign). 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‑to‑2 split. Overall, the majority of 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	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-4.496	Likely Benign	0.602	Likely Pathogenic	Likely Benign	0.13	Likely Benign	0.0	-0.18	Likely Benign	-0.03	Likely Benign	0.04	Likely Benign	0.271	Likely Benign	-4.38	Deleterious	0.456	Possibly Damaging	0.069	Benign	3.46	Benign	0.14	Tolerated			0.4035	0.5610		1	-1	3.1	-58.04
c.1966G>C	E656Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E656Q is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441225‑G‑C). Functional prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default; Rosetta reports an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑2 split. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000					Uncertain		1	6-33441225-G-C	1	6.20e-7	-9.145	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	-0.14	Likely Benign	0.0	-0.81	Ambiguous	-0.48	Likely Benign	0.25	Likely Benign	0.249	Likely Benign	-2.29	Neutral	0.980	Probably Damaging	0.528	Possibly Damaging	3.46	Benign	0.02	Affected	3.39	24	0.1739	0.6645		2	2	0.0	-0.98	224.3	1.7	0.0	0.1	0.1	0.0		X						Potentially Benign	The carboxylate side chain of Glu656, located on an α helix (res. Ser641-Glu666), frequently forms a hydrogen bond with the nearby residue Ser659 on the same α helix. In the variant simulations, the carboxamide side chain of Gln656 alternatively forms a hydrogen bond with either Ser659 or Glu548 on an opposing helix (res. Ala533-Val560).Although the frequent interaction between Gln656 and Glu548 may strengthen or stabilize the tertiary structure assembly, the effect is likely to be marginal.
c.1967A>C	E656A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 further reveal that AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus also indicates likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No prediction or stability result is missing or inconclusive. Based on the overall evidence, the variant is most likely pathogenic; this assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-14.373	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.0	0.10	Likely Benign	0.11	Likely Benign	-0.13	Likely Benign	0.499	Likely Benign	-5.38	Deleterious	0.985	Probably Damaging	0.755	Possibly Damaging	3.46	Benign	0.03	Affected			0.4244	0.6271		0	-1	5.3	-58.04
c.1967A>T	E656V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E656V has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, 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) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (8 of 13) indicate a pathogenic impact, 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	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-15.252	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-0.26	Likely Benign	0.0	-0.10	Likely Benign	-0.18	Likely Benign	-0.77	Ambiguous	0.509	Likely Pathogenic	-6.38	Deleterious	0.784	Possibly Damaging	0.223	Benign	3.46	Benign	0.02	Affected			0.0990	0.7057		-2	-2	7.7	-29.98
c.1969T>G	W657G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of other in silico predictors (AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FoldX, Rosetta, premPS, Foldetta) all classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant 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	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-12.559	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	3.04	Destabilizing	0.2	2.80	Destabilizing	2.92	Destabilizing	1.28	Destabilizing	0.389	Likely Benign	-11.16	Deleterious	0.999	Probably Damaging	0.941	Probably Damaging	3.46	Benign	0.15	Tolerated			0.4470	0.0885		-7	-2	0.5	-129.16
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.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.2021C>T	T674I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674I is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (ID 6‑33441280‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and ESM1b (polyPhen‑2 HumVar is benign). 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 pathogenic. Overall, the majority of evidence points to a benign effect, 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	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000								6-33441280-C-T	2	1.24e-6	-8.951	Likely Pathogenic	0.522	Ambiguous	Likely Benign	-0.05	Likely Benign	0.1	0.28	Likely Benign	0.12	Likely Benign	-0.04	Likely Benign	0.289	Likely Benign	-3.18	Deleterious	0.981	Probably Damaging	0.444	Benign	3.46	Benign	0.11	Tolerated	3.40	24	0.0898	0.6945		-1	0	5.2	12.05
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.2056G>C	G686R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta, Foldetta, and FATHMM, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) all predict a pathogenic impact; FoldX is listed as uncertain and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (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 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	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-14.801	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.79	Ambiguous	0.3	0.15	Likely Benign	0.47	Likely Benign	1.10	Destabilizing	0.503	Likely Pathogenic	-7.21	Deleterious	0.974	Probably Damaging	0.449	Possibly Damaging	3.46	Benign	0.00	Affected			0.0951	0.3580		-3	-2	-4.1	99.14
c.2080G>A	A694T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694T 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, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Taken together, the overwhelming majority of evidence indicates a benign effect for A694T, 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 Benign	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-3.565	Likely Benign	0.102	Likely Benign	Likely Benign	0.55	Ambiguous	0.1	0.11	Likely Benign	0.33	Likely Benign	-0.26	Likely Benign	0.095	Likely Benign	-0.71	Neutral	0.787	Possibly Damaging	0.098	Benign	3.46	Benign	0.17	Tolerated			0.1618	0.5440		1	0	-2.5	30.03
c.2098C>G	L700V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, protein‑stability methods predict a deleterious impact: FoldX and Rosetta both score the variant as pathogenic, and the combined Foldetta analysis (FoldX‑MD + Rosetta) also reports a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta remains pathogenic. Overall, the majority of predictions support a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-3.703	Likely Benign	0.192	Likely Benign	Likely Benign	2.52	Destabilizing	0.0	3.16	Destabilizing	2.84	Destabilizing	0.13	Likely Benign	0.056	Likely Benign	0.37	Neutral	0.003	Benign	0.005	Benign	3.46	Benign	0.76	Tolerated			0.1424	0.2460		2	1	0.4	-14.03
c.2104C>A	Q702K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702K 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports 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.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-8.750	Likely Pathogenic	0.338	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.26	Likely Benign	0.02	Likely Benign	0.08	Likely Benign	0.224	Likely Benign	-2.86	Deleterious	0.863	Possibly Damaging	0.773	Possibly Damaging	3.46	Benign	0.08	Tolerated			0.1346	0.2524		1	1	-0.4	0.04
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.2168C>A	T723K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while FoldX and AlphaMissense‑Default are uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the preponderance of evidence supports a benign classification for T723K, 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 Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-4.624	Likely Benign	0.482	Ambiguous	Likely Benign	-0.77	Ambiguous	0.1	-0.04	Likely Benign	-0.41	Likely Benign	0.25	Likely Benign	0.121	Likely Benign	-1.40	Neutral	0.674	Possibly Damaging	0.118	Benign	3.46	Benign	0.51	Tolerated			0.0924	0.2798		0	-1	-3.2	27.07
c.2189T>A	I730N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730N 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, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and SIFT. The remaining tools—premPS, ESM1b, 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) is inconclusive due to a 2‑to‑2 split, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the majority of evidence points to a benign 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.			0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-7.987	In-Between	0.369	Ambiguous	Likely Benign	0.09	Likely Benign	0.2	0.04	Likely Benign	0.07	Likely Benign	0.70	Ambiguous	0.080	Likely Benign	-1.60	Neutral	1.000	Probably Damaging	0.986	Probably Damaging	3.46	Benign	0.02	Affected			0.0969	0.0533		-2	-3	-8.0	0.94
c.325A>T	S109C 2D AIThe SynGAP1 missense variant S109C 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus (majority vote) also as Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign 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 Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-6.268	Likely Benign	0.761	Likely Pathogenic	Likely Benign										0.217	Likely Benign	-2.19	Neutral	0.983	Probably Damaging	0.431	Benign	3.46	Benign	0.00	Affected			0.1084	0.5354		0	-1	3.3	16.06
c.394T>C	F132L 2D AIThe SynGAP1 missense variant F132L is not reported in ClinVar (status: none) but is present in gnomAD (ID 6‑33432691‑T‑C). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Overall, the majority of consensus tools lean toward a benign interpretation, and the single high‑accuracy pathogenic prediction is counterbalanced by inconclusive consensus and missing folding‑stability data. Thus, the variant is most likely benign 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.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250								6-33432691-T-C			-5.401	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.165	Likely Benign	-2.99	Deleterious	0.000	Benign	0.002	Benign	3.46	Benign	0.00	Affected	3.61	5	0.2564	0.2669		0	2	1.0	-34.02
c.396C>A	F132L 2D AIThe SynGAP1 missense variant F132L 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 and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). Foldetta, a protein‑folding‑stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools (AlphaMissense‑Optimized and AlphaMissense‑Default) both predict pathogenicity, while the consensus and stability analyses are inconclusive or missing. Overall, the majority of individual predictors and the high‑accuracy tools lean toward a pathogenic effect, 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.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-5.401	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.137	Likely Benign	-2.99	Deleterious	0.000	Benign	0.002	Benign	3.46	Benign	0.00	Affected	3.61	5	0.2564	0.2669		0	2	1.0	-34.02
c.396C>G	F132L 2D AIThe SynGAP1 missense variant F132L 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 and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools (AlphaMissense‑Optimized and AlphaMissense‑Default) both predict pathogenicity, whereas the consensus and stability analyses are inconclusive or missing. Overall, the majority of individual predictors and the two high‑accuracy tools suggest a pathogenic effect, 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.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-5.401	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.137	Likely Benign	-2.99	Deleterious	0.000	Benign	0.002	Benign	3.46	Benign	0.00	Affected	3.61	5	0.2564	0.2669		0	2	1.0	-34.02
c.557T>G	L186W 2D AIThe SynGAP1 missense variant L186W has no ClinVar entry and is not reported 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 outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus 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 tools indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-16.177	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-4.78	Deleterious	0.996	Probably Damaging	0.819	Possibly Damaging	3.46	Benign	0.00	Affected			0.0539	0.3138		-2	-2	-4.7	73.05
c.67G>T	D23Y 2D AIThe SynGAP1 D23Y missense variant is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33420331‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. 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‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. 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.			0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375								6-33420331-G-T			-4.191	Likely Benign	0.729	Likely Pathogenic	Likely Benign										0.142	Likely Benign	-2.87	Deleterious	0.972	Probably Damaging	0.861	Possibly Damaging	3.46	Benign	0.00	Affected	4.32	1	0.1013	0.7951		-3	-4	2.2	48.09
c.1277A>C	N426T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change N426T lies in the GAP domain. It 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Predictions that are uncertain or inconclusive are FoldX, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta remains uncertain and is not taken as evidence. Overall, the majority of tools, including the high‑accuracy methods, predict a benign effect. This consensus 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.		GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-7.389	In-Between	0.194	Likely Benign	Likely Benign	0.84	Ambiguous	0.0	0.38	Likely Benign	0.61	Ambiguous	0.12	Likely Benign	0.126	Likely Benign	-3.14	Deleterious	0.983	Probably Damaging	0.926	Probably Damaging	3.47	Benign	0.10	Tolerated			0.1090	0.3002		0	0	2.8	-13.00
c.1277A>G	N426S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The high‑accuracy AlphaMissense‑Optimized score is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and the Foldetta stability assessment is inconclusive. No evidence from FoldX or Rosetta is available. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a ClinVar assertion. Therefore, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-5.215	Likely Benign	0.081	Likely Benign	Likely Benign	0.81	Ambiguous	0.0	0.52	Ambiguous	0.67	Ambiguous	0.03	Likely Benign	0.131	Likely Benign	-2.37	Neutral	0.998	Probably Damaging	0.921	Probably Damaging	3.47	Benign	0.33	Tolerated			0.2224	0.3188		1	1	2.7	-27.03
c.1286G>A	R429Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438191‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b, while premPS is inconclusive. The high‑accuracy consensus (SGM Consensus) – a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN – yields a “Likely Benign” result. AlphaMissense‑Optimized itself predicts benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Taken together, the preponderance of evidence points to a benign impact for R429Q, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000					Uncertain		2	6-33438191-G-A	10	6.20e-6	-8.227	Likely Pathogenic	0.143	Likely Benign	Likely Benign	0.45	Likely Benign	0.1	0.36	Likely Benign	0.41	Likely Benign	0.98	Ambiguous	0.156	Likely Benign	-1.25	Neutral	1.000	Probably Damaging	0.979	Probably Damaging	3.47	Benign	0.58	Tolerated	3.38	25	0.2518	0.1985		1	1	1.0	-28.06	235.8	59.5	0.0	0.0	-0.3	0.4		X						Potentially Pathogenic	The guanidinium group of the Arg429 side chain, located in an α helix (res. Met414-Glu436), either forms a salt bridge with the carboxylate group of an acidic residue (Asp474, Asp467) or an H-bond with the hydroxyl group of Ser471 in an opposing α helix (res. Ala461-Phe476). In the variant simulations, Gln429 cannot form ionic interactions with the acidic residues; however, the carboxamide group can form multiple H-bonds. The H-bonding coordination of the Asn429 side chain varied between the replica simulations. In one simulation, three H-bonds were formed simultaneously with the Asp467 side chain, the backbone carbonyl group of Asn426, and the amide group of Met430 at the end of the same α helix. The residue swap could affect the tertiary structure assembly during folding due to weaker bond formation, but no large-scale negative effects were seen during the simulations.
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.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.1324A>G	K442E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: 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 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 evidence decisively outweighs the others. Therefore, the variant’s pathogenicity remains uncertain; the predictions do not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-12.813	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	-0.05	Likely Benign	0.1	-0.21	Likely Benign	-0.13	Likely Benign	0.24	Likely Benign	0.324	Likely Benign	-3.34	Deleterious	0.997	Probably Damaging	0.966	Probably Damaging	3.47	Benign	0.16	Tolerated			0.2943	0.0789		0	1	0.4	0.94
c.1348G>T	A450S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A450S 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining methods—FoldX, Rosetta, Foldetta, and premPS—return uncertain or inconclusive results. 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 unavailable; Foldetta is uncertain. Overall, the balance of evidence (five benign versus four pathogenic predictions, with three uncertain) suggests the variant is most likely benign. 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	0.321458	Structured	0.306281	Uncertain	0.963	0.234	0.000											-9.257	Likely Pathogenic	0.274	Likely Benign	Likely Benign	0.81	Ambiguous	0.0	1.35	Ambiguous	1.08	Ambiguous	0.69	Ambiguous	0.268	Likely Benign	-2.70	Deleterious	0.965	Probably Damaging	0.972	Probably Damaging	3.47	Benign	0.10	Tolerated			0.2003	0.4322		1	1	-2.6	16.00
c.1385A>C	K462T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K462T 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. 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	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-11.586	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	1.08	Ambiguous	0.82	Ambiguous	0.30	Likely Benign	0.414	Likely Benign	-5.82	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.47	Benign	0.08	Tolerated			0.2095	0.3257		0	-1	3.2	-27.07
c.1389C>A	D463E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463E 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, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and premPS. Only PROVEAN predicts a pathogenic outcome, while Rosetta and AlphaMissense‑Default are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that 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	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-5.170	Likely Benign	0.527	Ambiguous	Likely Benign	-0.42	Likely Benign	0.1	0.50	Ambiguous	0.04	Likely Benign	0.47	Likely Benign	0.162	Likely Benign	-2.58	Deleterious	0.012	Benign	0.003	Benign	3.47	Benign	0.29	Tolerated			0.1330	0.5177		3	2	0.0	14.03
c.1389C>G	D463E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463E 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, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and premPS. Only PROVEAN predicts a pathogenic outcome, while Rosetta and AlphaMissense‑Default are uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign, and Foldetta also indicates benign stability. No prediction or stability result is missing or inconclusive. Overall, the variant is most likely benign based on the collective evidence, 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	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-5.170	Likely Benign	0.527	Ambiguous	Likely Benign	-0.42	Likely Benign	0.1	0.50	Ambiguous	0.04	Likely Benign	0.47	Likely Benign	0.162	Likely Benign	-2.58	Deleterious	0.012	Benign	0.003	Benign	3.47	Benign	0.29	Tolerated			0.1330	0.5177		3	2	0.0	14.03
c.1442A>G	H481R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H481R is not listed in ClinVar and has no reported allele in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by AlphaMissense‑Optimized, premPS, and Rosetta. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; and Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign impact. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion is not contradicted by the absence of a ClinVar classification. 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											-11.753	Likely Pathogenic	0.823	Likely Pathogenic	Ambiguous	-0.45	Likely Benign	0.1	0.68	Ambiguous	0.12	Likely Benign	0.59	Ambiguous	0.252	Likely Benign	-4.48	Deleterious	0.983	Probably Damaging	0.977	Probably Damaging	3.47	Benign	0.53	Tolerated			0.1515	0.1690		2	0	-1.3	19.05
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.1792C>A	L598I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L598I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and ESM1b. The remaining tools (FoldX, 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 benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign impact. 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	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-9.396	Likely Pathogenic	0.512	Ambiguous	Likely Benign	0.80	Ambiguous	0.0	0.38	Likely Benign	0.59	Ambiguous	0.78	Ambiguous	0.246	Likely Benign	-1.96	Neutral	0.988	Probably Damaging	0.910	Probably Damaging	3.47	Benign	0.10	Tolerated			0.0792	0.2000		2	2	0.7	0.00
c.1918A>C	T640P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640P is not reported in ClinVar and is absent from gnomAD. In silico predictors uniformly favor a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, SIFT, FATHMM, AlphaMissense-Default, and AlphaMissense-Optimized all indicate benign. No tool predicts pathogenicity. FoldX and ESM1b were inconclusive. High‑accuracy methods corroborate this: AlphaMissense-Optimized is benign, the SGM Consensus (majority vote of AlphaMissense-Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta (combining FoldX‑MD and Rosetta) also predicts benign. Consequently, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for T640P. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-7.594	In-Between	0.077	Likely Benign	Likely Benign	0.98	Ambiguous	0.3	-0.38	Likely Benign	0.30	Likely Benign	0.31	Likely Benign	0.313	Likely Benign	-0.91	Neutral	0.004	Benign	0.002	Benign	3.47	Benign	0.14	Tolerated			0.2179	0.4722		0	-1	-0.9	-3.99
c.1964T>C	L655P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L655P is catalogued in gnomAD (ID 6‑33441223‑T‑C) but has no ClinVar entry. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, SIFT, and FATHMM, whereas pathogenic calls are made by Rosetta, Foldetta, both polyPhen‑2 versions, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and premPS are uncertain. High‑accuracy assessments give AlphaMissense‑Optimized as pathogenic, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Overall, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000								6-33441223-T-C	1	6.20e-7	-9.771	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.33	Ambiguous	0.5	6.52	Destabilizing	3.93	Destabilizing	0.57	Ambiguous	0.126	Likely Benign	-1.36	Neutral	0.981	Probably Damaging	0.772	Possibly Damaging	3.47	Benign	0.32	Tolerated	3.39	24	0.3598	0.1274		-3	-3	-5.4	-16.04
c.1973G>C	G658A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect, and the SGM‑Consensus score indicates a likely benign outcome. No tool predicts pathogenicity. High‑accuracy assessments corroborate this view: AlphaMissense‑Optimized returns a benign prediction, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign result, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain outcome. Taken together, the evidence overwhelmingly supports a benign impact for G658A, 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 Benign	GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-4.303	Likely Benign	0.083	Likely Benign	Likely Benign	-0.34	Likely Benign	0.0	-0.75	Ambiguous	-0.55	Ambiguous	-0.18	Likely Benign	0.072	Likely Benign	-0.93	Neutral	0.002	Benign	0.001	Benign	3.47	Benign	0.36	Tolerated			0.3937	0.3352		1	0	2.2	14.03
c.2013C>A	D671E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D671E is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the substitution as benign. The only inconclusive result is AlphaMissense‑Default, which is listed as uncertain; all other high‑accuracy predictors support a benign outcome. In particular, AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. No pathogenic predictions are present. Therefore, based on the available computational evidence, the variant is most likely benign, 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 Benign	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-3.657	Likely Benign	0.371	Ambiguous	Likely Benign	-0.17	Likely Benign	0.1	0.22	Likely Benign	0.03	Likely Benign	0.03	Likely Benign	0.066	Likely Benign	-0.83	Neutral	0.013	Benign	0.009	Benign	3.47	Benign	0.53	Tolerated			0.1520	0.6388		3	2	0.0	14.03
c.2013C>G	D671E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D671E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. The high‑accuracy assessments are consistent: AlphaMissense‑Optimized indicates Benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Benign. With all available evidence pointing to a benign effect and no ClinVar record to contradict this, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-3.657	Likely Benign	0.371	Ambiguous	Likely Benign	-0.17	Likely Benign	0.1	0.22	Likely Benign	0.03	Likely Benign	0.03	Likely Benign	0.066	Likely Benign	-0.83	Neutral	0.013	Benign	0.009	Benign	3.47	Benign	0.53	Tolerated			0.1520	0.6388		3	2	0.0	14.03
c.2020A>T	T674S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, and AlphaMissense‑Default all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. With all available evidence pointing to a benign outcome and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-5.320	Likely Benign	0.082	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.44	Likely Benign	0.11	Likely Benign	-0.14	Likely Benign	0.084	Likely Benign	0.47	Neutral	0.107	Benign	0.033	Benign	3.47	Benign	1.00	Tolerated			0.3329	0.4938		1	1	-0.1	-14.03
c.2021C>G	T674S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, and AlphaMissense‑Default all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. With all available evidence pointing to a benign outcome and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-5.320	Likely Benign	0.082	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.44	Likely Benign	0.11	Likely Benign	-0.14	Likely Benign	0.088	Likely Benign	0.47	Neutral	0.107	Benign	0.033	Benign	3.47	Benign	1.00	Tolerated			0.3329	0.4938		1	1	-0.1	-14.03
c.2036T>A	F679Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679Y 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools give uncertain results: premPS and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the majority of evidence indicates that F679Y is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-5.842	Likely Benign	0.462	Ambiguous	Likely Benign	0.48	Likely Benign	0.2	0.13	Likely Benign	0.31	Likely Benign	0.71	Ambiguous	0.315	Likely Benign	-2.71	Deleterious	0.993	Probably Damaging	0.952	Probably Damaging	3.47	Benign	0.14	Tolerated			0.1306	0.1954		7	3	-4.1	16.00
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.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.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.2039A>T	E680V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E680V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, premPS, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Rosetta is inconclusive. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, more tools (seven) predict pathogenicity than benign (five), and the high‑accuracy consensus leans toward pathogenic. Thus, 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	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-12.051	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	0.46	Likely Benign	0.3	-1.08	Ambiguous	-0.31	Likely Benign	0.18	Likely Benign	0.454	Likely Benign	-6.21	Deleterious	0.988	Probably Damaging	0.606	Possibly Damaging	3.47	Benign	0.01	Affected			0.1091	0.7518		-2	-2	7.7	-29.98
c.2064G>C	E688D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Tools that predict a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods specifically give AlphaMissense‑Optimized a pathogenic prediction, SGM‑Consensus a pathogenic prediction, and Foldetta an uncertain result. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by 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	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-11.890	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.79	Ambiguous	0.5	0.53	Ambiguous	1.16	Ambiguous	0.91	Ambiguous	0.302	Likely Benign	-2.89	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.47	Benign	0.08	Tolerated			0.1722	0.3492		3	2	0.0	-14.03
c.2064G>T	E688D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Tools that predict a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods specifically give: AlphaMissense‑Optimized – pathogenic; SGM‑Consensus – pathogenic; Foldetta – uncertain. Taken together, the majority of evidence points to a pathogenic impact. 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	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-11.890	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.79	Ambiguous	0.5	0.53	Ambiguous	1.16	Ambiguous	0.91	Ambiguous	0.302	Likely Benign	-2.89	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.47	Benign	0.08	Tolerated			0.1722	0.3492		3	2	0.0	-14.03
c.2126T>C	L709P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709P is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from FoldX, Rosetta, Foldetta, polyPhen2_HumDiv, polyPhen2_HumVar, and AlphaMissense‑Default. High‑accuracy tools give mixed results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, FATHMM, PROVEAN) also predicts benign; Foldetta predicts pathogenic. Because the majority of standard predictors and the SGM Consensus favor benign, the variant is most likely benign, and this is consistent with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-7.517	In-Between	0.767	Likely Pathogenic	Likely Benign	2.81	Destabilizing	0.0	5.65	Destabilizing	4.23	Destabilizing	0.31	Likely Benign	0.167	Likely Benign	-1.93	Neutral	1.000	Probably Damaging	0.975	Probably Damaging	3.47	Benign	0.37	Tolerated			0.3004	0.0825		-3	-3	-5.4	-16.04
c.326G>T	S109I 2D AIThe SynGAP1 missense variant S109I 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, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, 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, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence (five benign vs. three pathogenic predictions) points toward a benign impact. This conclusion 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.			0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-5.195	Likely Benign	0.927	Likely Pathogenic	Ambiguous										0.200	Likely Benign	-2.56	Deleterious	0.267	Benign	0.039	Benign	3.47	Benign	0.00	Affected			0.0910	0.4930		-1	-2	5.3	26.08
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.407G>C	R136P 2D AIThe SynGAP1 missense variant R136P is listed in ClinVar (ID 579340.0) with an “Uncertain” status and is not reported 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—predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates 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, 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		1				-11.952	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.277	Likely Benign	-3.72	Deleterious	0.910	Possibly Damaging	0.578	Possibly Damaging	3.47	Benign	0.00	Affected	3.61	5	0.2063	0.4426		0	-2	2.9	-59.07
c.425A>C	K142T 2D AIThe SynGAP1 missense variant K142T 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, 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; Foldetta results are unavailable. Based on the collective evidence, 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.013	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.251	Likely Benign	-3.77	Deleterious	0.247	Benign	0.166	Benign	3.47	Benign	0.00	Affected			0.2034	0.2708		0	-1	3.2	-27.07
c.426A>C	K142N 2D AIThe SynGAP1 missense variant K142N 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.169	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.097	Likely Benign	-3.13	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.47	Benign	0.00	Affected			0.3586	0.1437		1	0	0.4	-14.07
c.426A>T	K142N 2D AIThe SynGAP1 missense variant K142N 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.169	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.096	Likely Benign	-3.13	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.47	Benign	0.00	Affected			0.3586	0.1437		1	0	0.4	-14.07
c.550G>C	E184Q 2D AIThe SynGAP1 missense variant E184Q 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, 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 none is assigned. 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											-11.927	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-2.55	Deleterious	0.990	Probably Damaging	0.815	Possibly Damaging	3.47	Benign	0.00	Affected			0.1688	0.7914		2	2	0.0	-0.98
c.67G>C	D23H 2D AIThe SynGAP1 D23H missense 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, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). 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.	Likely Benign		0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-3.801	Likely Benign	0.867	Likely Pathogenic	Ambiguous										0.103	Likely Benign	-2.46	Neutral	0.972	Probably Damaging	0.861	Possibly Damaging	3.47	Benign	0.00	Affected			0.2644	0.9017		1	-1	0.3	22.05
c.1282T>A	Y428N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428N 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, which classifies the change as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports 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 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 (none is available). 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											-12.164	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	2.34	Destabilizing	0.0	3.81	Destabilizing	3.08	Destabilizing	1.85	Destabilizing	0.533	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.03	Affected			0.2607	0.0971		-2	-2	-2.2	-49.07
c.1289T>C	M430T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430T is reported in gnomAD (6‑33438194‑T‑C) and has no ClinVar entry. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, FoldX (uncertain), Rosetta, Foldetta (uncertain), premPS, 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 classify it as benign or likely benign. No tool predicts pathogenicity. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign, the SGM Consensus is likely benign, and Foldetta is uncertain. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Thus, the variant is most likely benign, and this is not contradictory to ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000								6-33438194-T-C	1	6.19e-7	-3.430	Likely Benign	0.107	Likely Benign	Likely Benign	1.89	Ambiguous	0.1	0.01	Likely Benign	0.95	Ambiguous	0.43	Likely Benign	0.103	Likely Benign	-1.48	Neutral	0.016	Benign	0.010	Benign	3.48	Benign	0.40	Tolerated	3.37	29	0.2002	0.3184		-1	-1	-2.6	-30.09
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.1319A>C	N440T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly favor a benign effect: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, REVEL, premPS, Rosetta, Foldetta, and the SGM‑Consensus (majority vote) all predict benign or likely benign. No tool predicts pathogenicity; the only inconclusive result is from FoldX, which is listed as uncertain. High‑accuracy methods corroborate the benign assessment: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Therefore, based on the available predictions, 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.	Likely Benign	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000											-5.371	Likely Benign	0.143	Likely Benign	Likely Benign	0.58	Ambiguous	0.0	0.16	Likely Benign	0.37	Likely Benign	0.11	Likely Benign	0.079	Likely Benign	-1.27	Neutral	0.007	Benign	0.005	Benign	3.48	Benign	0.14	Tolerated			0.0969	0.3341		0	0	2.8	-13.00
c.1357C>A	H453N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H453N is not reported in ClinVar and is absent from gnomAD. 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, ESM1b, and AlphaMissense‑Default. A third set of methods (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) yield 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, predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. Overall, the majority of evidence points toward a pathogenic effect for H453N. 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	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-8.416	Likely Pathogenic	0.789	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.1	0.97	Ambiguous	0.95	Ambiguous	0.78	Ambiguous	0.347	Likely Benign	-6.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.48	Benign	0.09	Tolerated			0.1435	0.2548		2	1	-0.3	-23.04
c.1357C>G	H453D 2D 3DClick to see structure in 3D Viewer AISynGAP1 H453D 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, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods reinforce a pathogenic interpretation: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenicity. premPS remains uncertain. Overall, the majority of evidence points to a pathogenic effect for H453D, 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	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-15.256	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.0	2.68	Destabilizing	3.01	Destabilizing	0.97	Ambiguous	0.443	Likely Benign	-8.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.48	Benign	0.09	Tolerated			0.2225	0.1815		1	-1	-0.3	-22.05
c.1372A>T	T458S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T458S missense variant has no ClinVar entry and is not present in gnomAD. Functional prediction tools cluster into two groups: benign calls from REVEL, FoldX, Rosetta, SIFT, and FATHMM; pathogenic calls from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments further split the signal: AlphaMissense‑Optimized remains uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Because the majority of standard predictors are evenly divided and the high‑accuracy methods disagree, the variant’s effect cannot be confidently classified as benign or pathogenic. Thus, the variant is of uncertain significance, and this uncertainty 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	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-8.465	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.1	0.35	Likely Benign	0.40	Likely Benign	0.55	Ambiguous	0.260	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.48	Benign	0.13	Tolerated			0.3525	0.4349		1	1	-0.1	-14.03
c.1441C>G	H481D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H481D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, FoldX, SIFT, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic signal: the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Uncertain results from AlphaMissense‑Optimized, Foldetta, premPS, and Rosetta are treated as unavailable. Overall, the preponderance of evidence points to a pathogenic effect for H481D, 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	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-11.822	Likely Pathogenic	0.812	Likely Pathogenic	Ambiguous	-0.09	Likely Benign	0.1	0.54	Ambiguous	0.23	Likely Benign	0.70	Ambiguous	0.273	Likely Benign	-5.41	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.50	Tolerated			0.2109	0.1058		1	-1	-0.3	-22.05
c.1552T>A	Y518N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Foldetta) uniformly predict a pathogenic impact. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show that 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. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is not contradicted by 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	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.036	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	2.99	Destabilizing	0.8	1.50	Ambiguous	2.25	Destabilizing	1.29	Destabilizing	0.506	Likely Pathogenic	-8.45	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.04	Affected			0.1791	0.0212		-2	-2	-2.2	-49.07
c.1675T>C	C559R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C559R 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, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and premPS. 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 (six pathogenic vs five benign) lean toward a pathogenic interpretation, and this does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Thus, the variant is most likely pathogenic based on current predictive evidence. 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											-9.509	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	-1.03	Ambiguous	0.1	-0.38	Likely Benign	-0.71	Ambiguous	0.79	Ambiguous	0.498	Likely Benign	-8.58	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.46	Tolerated			0.2498	0.1720		-4	-3	-7.0	53.05
c.1689G>C	R563S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R563S missense change is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) return uncertain or inconclusive results. High‑accuracy assessments are likewise ambiguous: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑to‑2 tie and therefore unavailable; Foldetta also reports an uncertain stability change. Consequently, the evidence does not strongly support either benign or pathogenic status. The variant’s classification is therefore inconclusive and does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-6.503	Likely Benign	0.949	Likely Pathogenic	Ambiguous	1.16	Ambiguous	0.1	1.46	Ambiguous	1.31	Ambiguous	0.69	Ambiguous	0.251	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.23	Tolerated			0.3031	0.2534		0	-1	3.7	-69.11
c.1689G>T	R563S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R563S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, Foldetta, premPS, 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 of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑to‑2 tie, and Foldetta is uncertain. Consequently, the evidence does not strongly favor either outcome. Based on the current predictions, 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.		GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-6.503	Likely Benign	0.949	Likely Pathogenic	Ambiguous	1.16	Ambiguous	0.1	1.46	Ambiguous	1.31	Ambiguous	0.69	Ambiguous	0.251	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.23	Tolerated			0.3031	0.2534		0	-1	3.7	-69.11
c.1700A>T	E567V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E567V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Rosetta alone is inconclusive and treated as unavailable. Overall, the majority of evidence points to a pathogenic effect for E567V, 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	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-15.638	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.1	0.59	Ambiguous	0.43	Likely Benign	0.38	Likely Benign	0.440	Likely Benign	-6.77	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.06	Tolerated			0.0573	0.6175		-2	-2	7.7	-29.98
c.1771G>A	A591T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591T is listed in ClinVar with an uncertain significance designation and is observed in gnomAD (variant ID 6‑33440823‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic outcome. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability metrics are available. Overall, the balance of evidence favors a pathogenic interpretation, 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	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000					Conflicting		3	6-33440823-G-A	18	1.12e-5	-9.572	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	1.61	Ambiguous	0.2	1.00	Ambiguous	1.31	Ambiguous	1.19	Destabilizing	0.270	Likely Benign	-3.40	Deleterious	0.955	Possibly Damaging	0.209	Benign	3.48	Benign	0.01	Affected	3.37	35	0.1225	0.4155		1	0	-2.5	30.03	202.9	-43.4	0.2	0.0	0.7	0.1						X		Potentially Benign	The methyl group of the Ala591 side chain, located in the middle of an α helix (res. Glu582-Met603), packs against hydrophobic residues (e.g., Ile483, Phe484) of an opposing partially helical loop (res. Phe476-Asn487).In the variant simulations, the hydroxyl group of Thr591 can form hydrogen bonds with the backbone carbonyl of Ile843 in the opposing loop or the backbone carbonyl group of Arg587. These interactions could either reinforce the tertiary assembly or weaken the α helix unity. Additionally, the Thr591 side chain can hydrogen bond with the guanidinium group of the Arg587 side chain, potentially strengthening the α helix unity.Overall, the residue swap does not seem to cause any major negative effects on the protein structure.
c.1841A>C	Y614S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y614S is not reported in ClinVar and is present in gnomAD (ID 6‑33440893‑A‑C). Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas the majority of algorithms—AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), premPS, Rosetta, Foldetta, and the SGM Consensus—indicate pathogenicity; FoldX remains uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification, 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	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000								6-33440893-A-C	1	6.20e-7	-12.709	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.4	3.25	Destabilizing	2.50	Destabilizing	2.05	Destabilizing	0.482	Likely Benign	-8.83	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.09	Tolerated	3.37	35	0.4155	0.1220		-2	-3	0.5	-76.10
c.1939G>A	G647S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from Rosetta and premPS, which are treated as unavailable. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the evidence strongly favors a benign classification, and this is consistent with its absence from ClinVar. The variant is most likely benign, and this is consistent with its absence from ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-2.175	Likely Benign	0.082	Likely Benign	Likely Benign	0.05	Likely Benign	0.1	-0.75	Ambiguous	-0.35	Likely Benign	-0.56	Ambiguous	0.037	Likely Benign	0.65	Neutral	0.002	Benign	0.004	Benign	3.48	Benign	0.89	Tolerated			0.2409	0.3959		1	0	-0.4	30.03
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.1953G>C	E651D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E651D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen2_HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign prediction. No prediction tool or stability analysis is inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-3.220	Likely Benign	0.231	Likely Benign	Likely Benign	0.16	Likely Benign	0.1	0.33	Likely Benign	0.25	Likely Benign	-0.29	Likely Benign	0.153	Likely Benign	-0.13	Neutral	0.906	Possibly Damaging	0.429	Benign	3.48	Benign	0.53	Tolerated			0.1813	0.3762		3	2	0.0	-14.03
c.1953G>T	E651D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E651D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only polyPhen2_HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign prediction. No prediction tool or stability analysis is inconclusive or missing. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-3.220	Likely Benign	0.231	Likely Benign	Likely Benign	0.16	Likely Benign	0.1	0.33	Likely Benign	0.25	Likely Benign	-0.29	Likely Benign	0.153	Likely Benign	-0.13	Neutral	0.906	Possibly Damaging	0.429	Benign	3.48	Benign	0.53	Tolerated			0.1813	0.3762		3	2	0.0	-14.03
c.1969T>A	W657R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score, which is labeled Likely Pathogenic. 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, and the Foldetta stability analysis is inconclusive. Overall, the majority of evidence points to a pathogenic impact for W657R, 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	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-13.391	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.2	1.64	Ambiguous	1.60	Ambiguous	1.29	Destabilizing	0.461	Likely Benign	-11.96	Deleterious	0.999	Probably Damaging	0.964	Probably Damaging	3.48	Benign	0.07	Tolerated			0.4684	0.0000		2	-3	-3.6	-30.03
c.1969T>C	W657R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority of the four high‑accuracy tools) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. FoldX and Rosetta individually report uncertain effects on protein stability. 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 (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-13.391	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.2	1.64	Ambiguous	1.60	Ambiguous	1.29	Destabilizing	0.461	Likely Benign	-11.96	Deleterious	0.999	Probably Damaging	0.964	Probably Damaging	3.48	Benign	0.07	Tolerated			0.4684	0.0000		2	-3	-3.6	-30.03
c.1985A>G	Q662R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess sequence conservation, structural impact, or functional effect all converge on a benign outcome: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, FATHMM, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, FoldX, and Rosetta all predict benign. No tool in the dataset indicates pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Thus, based on the available predictions, the variant is most likely benign, 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 Benign	GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-6.678	Likely Benign	0.300	Likely Benign	Likely Benign	-0.41	Likely Benign	0.0	0.10	Likely Benign	-0.16	Likely Benign	-0.42	Likely Benign	0.159	Likely Benign	0.49	Neutral	0.428	Benign	0.095	Benign	3.48	Benign	1.00	Tolerated			0.2023	0.1391		1	1	-1.0	28.06
c.2072C>G	T691R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from 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, labels the variant 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 Uncertain. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-12.228	Likely Pathogenic	0.621	Likely Pathogenic	Likely Benign	-1.27	Ambiguous	0.3	-0.94	Ambiguous	-1.11	Ambiguous	1.35	Destabilizing	0.180	Likely Benign	-3.66	Deleterious	0.993	Probably Damaging	0.566	Possibly Damaging	3.48	Benign	0.02	Affected			0.0729	0.2478		-1	-1	-3.8	55.08
c.2081C>A	A694D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A694D 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, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, SIFT, 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 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the variant’s functional impact remains ambiguous. The predictions do not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-9.542	Likely Pathogenic	0.841	Likely Pathogenic	Ambiguous	0.35	Likely Benign	0.1	1.04	Ambiguous	0.70	Ambiguous	1.01	Destabilizing	0.163	Likely Benign	-2.47	Neutral	0.918	Possibly Damaging	0.375	Benign	3.48	Benign	0.05	Affected			0.2085	0.2216		0	-2	-5.3	44.01
c.2091G>C	W697C 2D 3DClick to see structure in 3D Viewer AISynGAP1 W697C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments are likewise ambiguous: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the evidence does not favor either outcome; the variant’s impact remains indeterminate. This lack of consensus does not contradict ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-5.683	Likely Benign	0.811	Likely Pathogenic	Ambiguous	1.84	Ambiguous	0.1	1.01	Ambiguous	1.43	Ambiguous	0.98	Ambiguous	0.318	Likely Benign	-8.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.48	Benign	0.10	Tolerated			0.3575	0.1015		-8	-2	3.4	-83.07
c.2091G>T	W697C 2D 3DClick to see structure in 3D Viewer AISynGAP1 W697C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) yield uncertain or missing results. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie; and Foldetta is uncertain. Consequently, the evidence does not strongly favor either outcome. The variant is therefore best classified as of uncertain significance; 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	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-5.683	Likely Benign	0.811	Likely Pathogenic	Ambiguous	1.84	Ambiguous	0.1	1.01	Ambiguous	1.43	Ambiguous	0.98	Ambiguous	0.318	Likely Benign	-8.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.48	Benign	0.10	Tolerated			0.3575	0.1015		-8	-2	3.4	-83.07
c.2095G>C	V699L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V699L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome, while FoldX, premPS, and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority; and Foldetta also predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the variant is most likely benign based on the preponderance of evidence, and this assessment does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000											-8.301	Likely Pathogenic	0.558	Ambiguous	Likely Benign	-0.58	Ambiguous	0.1	-0.36	Likely Benign	-0.47	Likely Benign	0.69	Ambiguous	0.150	Likely Benign	-2.14	Neutral	0.448	Benign	0.153	Benign	3.48	Benign	0.10	Tolerated			0.0900	0.3289		2	1	-0.4	14.03
c.2095G>T	V699L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V699L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome, while FoldX, premPS, and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority; and Foldetta also predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the variant is most likely benign based on the consensus of the available tools, and this benign prediction 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.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000											-8.301	Likely Pathogenic	0.558	Ambiguous	Likely Benign	-0.58	Ambiguous	0.1	-0.36	Likely Benign	-0.47	Likely Benign	0.69	Ambiguous	0.150	Likely Benign	-2.14	Neutral	0.448	Benign	0.153	Benign	3.48	Benign	0.10	Tolerated			0.0900	0.3289		2	1	-0.4	14.03
c.2101C>T	P701S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P701S (ClinVar ID 2995856.0) is listed as “Uncertain” in ClinVar and is present in gnomAD (ID 6‑33441360‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). No tool in the dataset predicts a pathogenic outcome; all remaining predictions are either benign or uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000					Uncertain		1	6-33441360-C-T	3	1.86e-6	-4.375	Likely Benign	0.221	Likely Benign	Likely Benign	1.33	Ambiguous	0.0	0.12	Likely Benign	0.73	Ambiguous	-0.36	Likely Benign	0.132	Likely Benign	0.78	Neutral	0.044	Benign	0.025	Benign	3.48	Benign	1.00	Tolerated	3.47	10	0.3149	0.3782		-1	1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2188A>G	I730V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730V is reported as “Likely Benign” in ClinVar and is not present in gnomAD. All available in‑silico predictors classify the change as benign: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Consequently, 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		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-3.960	Likely Benign	0.091	Likely Benign	Likely Benign	0.25	Likely Benign	0.1	0.04	Likely Benign	0.15	Likely Benign	0.03	Likely Benign	0.028	Likely Benign	-0.14	Neutral	0.112	Benign	0.033	Benign	3.48	Benign	0.39	Tolerated			0.1010	0.2303		4	3	-0.3	-14.03
c.325A>C	S109R 2D AIThe SynGAP1 missense variant S109R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM, whereas pathogenic calls come from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments highlight that AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts benign impact; Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign effect for S109R, 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 Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-4.830	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.225	Likely Benign	-1.80	Neutral	0.002	Benign	0.001	Benign	3.48	Benign	0.00	Affected			0.0884	0.2700		0	-1	-3.7	69.11
c.327T>A	S109R 2D AIThe SynGAP1 missense variant S109R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains benign; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, and this is not contradicted by any 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.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-4.830	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-1.80	Neutral	0.002	Benign	0.001	Benign	3.48	Benign	0.00	Affected			0.0884	0.2700		0	-1	-3.7	69.11
c.327T>G	S109R 2D AIThe SynGAP1 missense variant S109R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give mixed results: AlphaMissense‑Optimized reports a pathogenic effect, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, with one high‑accuracy tool suggesting pathogenicity, and there is no ClinVar status to contradict these findings. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-4.830	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-1.80	Neutral	0.002	Benign	0.001	Benign	3.48	Benign	0.00	Affected			0.0884	0.2700		0	-1	-3.7	69.11
c.407G>T	R136L 2D AIThe SynGAP1 missense variant R136L is catalogued in gnomAD (ID 6‑33432704‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions arise from PROVEAN, 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 Pathogenic, and the SGM‑Consensus (majority vote) 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, and this assessment does not conflict with ClinVar, which currently has no classification for R136L. 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								6-33432704-G-T	1	7.05e-7	-11.512	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.347	Likely Benign	-4.19	Deleterious	0.190	Benign	0.037	Benign	3.48	Benign	0.01	Affected	3.61	5	0.1718	0.4475		-2	-3	8.3	-43.03
c.419C>A	S140Y 2D AIThe SynGAP1 missense variant S140Y 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, and AlphaMissense‑Default—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. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the S140Y 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											-13.071	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.252	Likely Benign	-3.88	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	3.48	Benign	0.00	Affected			0.0597	0.5849		-3	-2	-0.5	76.10
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.551A>C	E184A 2D AIThe SynGAP1 missense variant E184A has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (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 supports a pathogenic effect for E184A. 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		0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-11.486	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.338	Likely Benign	-4.98	Deleterious	0.868	Possibly Damaging	0.344	Benign	3.48	Benign	0.00	Affected			0.4419	0.7381		0	-1	5.3	-58.04
c.68A>T	D23V 2D AIThe SynGAP1 D23V 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, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. 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 and thus unavailable; Foldetta predictions are not provided. Overall, more tools (five) 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.			0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-3.244	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.137	Likely Benign	-2.72	Deleterious	0.972	Probably Damaging	0.804	Possibly Damaging	3.48	Benign	0.00	Affected			0.1515	0.8367		-2	-3	7.7	-15.96
c.1309C>T	P437S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437S is not reported in ClinVar (ClinVar ID: None) but is present in gnomAD (ID 6‑33438214‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome; the remaining methods (FoldX, Foldetta, premPS, AlphaMissense‑Default) are uncertain 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 balance of evidence favors a pathogenic interpretation. 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.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000								6-33438214-C-T	2	1.24e-6	-11.964	Likely Pathogenic	0.518	Ambiguous	Likely Benign	1.14	Ambiguous	0.0	-3.31	Stabilizing	-1.09	Ambiguous	0.60	Ambiguous	0.226	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.49	Benign	0.01	Affected	3.38	26	0.3548	0.4843		-1	1	0.8	-10.04
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.1384A>G	K462E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462E 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. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta is uncertain. Overall, the majority of predictions (7 pathogenic vs. 5 benign) and the high‑accuracy tools support a pathogenic classification. Thus, 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	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-14.696	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.34	Likely Benign	0.0	1.56	Ambiguous	0.95	Ambiguous	0.33	Likely Benign	0.433	Likely Benign	-3.88	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.49	Benign	0.15	Tolerated			0.4145	0.1022		0	1	0.4	0.94
c.1426T>G	F476V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F476V 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 agree on a pathogenic effect are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and Foldetta. Tools with uncertain or mixed outputs are Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a pathogenic impact. Overall, the majority of evidence points toward a pathogenic effect. The variant is most likely pathogenic 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.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-12.329	Likely Pathogenic	0.918	Likely Pathogenic	Ambiguous	3.01	Destabilizing	0.2	1.90	Ambiguous	2.46	Destabilizing	0.64	Ambiguous	0.353	Likely Benign	-1.63	Neutral	0.996	Probably Damaging	0.993	Probably Damaging	3.49	Benign	0.53	Tolerated			0.1478	0.2251		-1	-1	1.4	-48.04
c.1432G>A	E478K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478K 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, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as benign. Overall, the majority of evidence (eight benign versus five pathogenic predictions) 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.	Likely Pathogenic	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-12.654	Likely Pathogenic	0.899	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.0	0.12	Likely Benign	0.18	Likely Benign	-0.02	Likely Benign	0.309	Likely Benign	-3.45	Deleterious	0.320	Benign	0.117	Benign	3.49	Benign	0.05	Affected			0.2066	0.6192		0	1	-0.4	-0.94
c.1660G>C	V554L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V554L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome, while FoldX, premPS, and ESM1b are uncertain. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the variant is most likely benign based on the available computational evidence, 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	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000											-7.884	In-Between	0.645	Likely Pathogenic	Likely Benign	-1.14	Ambiguous	0.0	0.29	Likely Benign	-0.43	Likely Benign	0.56	Ambiguous	0.162	Likely Benign	-1.54	Neutral	0.204	Benign	0.053	Benign	3.49	Benign	0.08	Tolerated			0.0991	0.2998		2	1	-0.4	14.03
c.1660G>T	V554L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V554L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome, while FoldX, premPS, and ESM1b are uncertain. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the variant is most likely benign based on the available computational evidence, 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	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000											-7.884	In-Between	0.645	Likely Pathogenic	Likely Benign	-1.14	Ambiguous	0.0	0.29	Likely Benign	-0.43	Likely Benign	0.56	Ambiguous	0.162	Likely Benign	-1.54	Neutral	0.204	Benign	0.053	Benign	3.49	Benign	0.08	Tolerated			0.0991	0.2998		2	1	-0.4	14.03
c.1688G>C	R563T 2D 3DClick to see structure in 3D Viewer AISynGAP1 R563T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, ESM1b, AlphaMissense‑Optimized, and Foldetta—give uncertain or inconclusive results. High‑accuracy methods provide the following: AlphaMissense‑Optimized is unavailable; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic; Foldetta is unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-7.088	In-Between	0.913	Likely Pathogenic	Ambiguous	1.13	Ambiguous	0.1	0.77	Ambiguous	0.95	Ambiguous	0.18	Likely Benign	0.307	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.49	Benign	0.23	Tolerated			0.2115	0.3148		-1	-1	3.8	-55.08
c.1931A>T	D644V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D644V 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, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN 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) is inconclusive because it yields a 2‑to‑2 split. Overall, the majority of evidence points to 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	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-6.230	Likely Benign	0.636	Likely Pathogenic	Likely Benign	0.50	Ambiguous	0.0	-0.35	Likely Benign	0.08	Likely Benign	-0.03	Likely Benign	0.347	Likely Benign	-4.96	Deleterious	0.198	Benign	0.052	Benign	3.49	Benign	0.11	Tolerated			0.0951	0.6267		-2	-3	7.7	-15.96
c.1939G>C	G647R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G647R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. In contrast, AlphaMissense‑Default and polyPhen‑2 HumDiv predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. No evidence from FoldX or Rosetta alone is available. Overall, the preponderance of evidence supports a benign classification, and this is consistent with the lack of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-6.590	Likely Benign	0.636	Likely Pathogenic	Likely Benign	-0.51	Ambiguous	0.1	-0.97	Ambiguous	-0.74	Ambiguous	0.29	Likely Benign	0.097	Likely Benign	-1.81	Neutral	0.787	Possibly Damaging	0.349	Benign	3.49	Benign	0.17	Tolerated			0.1020	0.3712		-3	-2	-4.1	99.14
c.1942T>G	F648V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include SIFT and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—predict it to be pathogenic. High‑accuracy methods give consistent results: AlphaMissense‑Optimized indicates pathogenicity; 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 outputs, also predicts a destabilizing, pathogenic effect. No prediction is missing or inconclusive. Overall, the evidence overwhelmingly supports a pathogenic classification, 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	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-11.574	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.1	2.80	Destabilizing	2.96	Destabilizing	1.14	Destabilizing	0.514	Likely Pathogenic	-6.98	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	3.49	Benign	0.06	Tolerated			0.1848	0.1983		-1	-1	1.4	-48.04
c.1982A>T	Q661L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, 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, so it is not used as evidence. Overall, the majority of predictions support a pathogenic impact, and this is consistent with the lack of ClinVar annotation. Therefore, 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	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-9.003	Likely Pathogenic	0.613	Likely Pathogenic	Likely Benign	-0.19	Likely Benign	0.1	-1.12	Ambiguous	-0.66	Ambiguous	0.36	Likely Benign	0.391	Likely Benign	-5.11	Deleterious	0.976	Probably Damaging	0.567	Possibly Damaging	3.49	Benign	0.02	Affected			0.0834	0.4675		-2	-2	7.3	-14.97
c.1984C>A	Q662K 2D AIThe SynGAP1 missense variant Q662K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while only ESM1b predicts pathogenicity. When high‑accuracy methods are considered separately, AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a Likely Benign verdict, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a benign effect. No conflicting evidence is present. Therefore, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-8.892	Likely Pathogenic	0.309	Likely Benign	Likely Benign	-0.02	Likely Benign	0.2	0.03	Likely Benign	0.01	Likely Benign	-0.04	Likely Benign	0.108	Likely Benign	-0.80	Neutral	0.321	Benign	0.030	Benign	3.49	Benign	0.37	Tolerated			0.2391	0.3198		1	1	-0.4	0.04
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.2038G>A	E680K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E680K 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 HumVar, and FATHMM. Those that predict a pathogenic effect are SIFT, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. 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. With a majority of individual tools and the SGM‑Consensus indicating pathogenicity, 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	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-12.728	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous	-0.10	Likely Benign	0.4	-0.15	Likely Benign	-0.13	Likely Benign	0.33	Likely Benign	0.417	Likely Benign	-3.54	Deleterious	0.959	Probably Damaging	0.411	Benign	3.49	Benign	0.02	Affected			0.3048	0.7553		0	1	-0.4	-0.94
c.2071A>G	T691A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while premPS and ESM1b are uncertain. The SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction contradicts the ClinVar status, which is currently unreported. Based on the preponderance of evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-7.840	In-Between	0.086	Likely Benign	Likely Benign	-0.11	Likely Benign	0.0	0.22	Likely Benign	0.06	Likely Benign	0.69	Ambiguous	0.063	Likely Benign	-1.84	Neutral	0.751	Possibly Damaging	0.131	Benign	3.49	Benign	0.33	Tolerated			0.2819	0.3251		1	0	2.5	-30.03
c.2071A>T	T691S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, 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; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, 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 Benign	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-9.274	Likely Pathogenic	0.123	Likely Benign	Likely Benign	0.44	Likely Benign	0.1	0.23	Likely Benign	0.34	Likely Benign	0.88	Ambiguous	0.041	Likely Benign	-1.67	Neutral	0.860	Possibly Damaging	0.584	Possibly Damaging	3.49	Benign	0.61	Tolerated			0.2213	0.3343		1	1	-0.1	-14.03
c.2072C>T	T691I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691I is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (gnomAD ID: 6‑33441331‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from FoldX, Foldetta, and premPS. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta remains uncertain. Overall, the evidence overwhelmingly indicates that T691I is most likely benign, 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 Benign	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000								6-33441331-C-T	1	6.20e-7	-5.857	Likely Benign	0.202	Likely Benign	Likely Benign	-1.08	Ambiguous	0.1	-2.12	Stabilizing	-1.60	Ambiguous	-0.61	Ambiguous	0.052	Likely Benign	-1.19	Neutral	0.040	Benign	0.003	Benign	3.49	Benign	0.34	Tolerated	3.43	14	0.0644	0.5397		-1	0	5.2	12.05
c.2111G>T	S704I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704I lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) report a pathogenic or likely pathogenic outcome. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy methods specifically give AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall consensus, 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	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-14.222	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.1	1.32	Ambiguous	1.48	Ambiguous	0.29	Likely Benign	0.232	Likely Benign	-4.05	Deleterious	0.997	Probably Damaging	0.758	Possibly Damaging	3.49	Benign	0.02	Affected			0.0727	0.4798		-1	-2	5.3	26.08
c.2167A>C	T723P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723P is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The 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 pathogenic. premPS is uncertain and does not influence the overall assessment. Overall, the majority of tools and the high‑accuracy methods support a pathogenic effect. Thus, 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	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-9.231	Likely Pathogenic	0.741	Likely Pathogenic	Likely Benign	3.98	Destabilizing	0.1	6.10	Destabilizing	5.04	Destabilizing	0.54	Ambiguous	0.085	Likely Benign	-2.51	Deleterious	0.995	Probably Damaging	0.929	Probably Damaging	3.49	Benign	0.04	Affected			0.1826	0.4406		0	-1	-0.9	-3.99
c.2189T>C	I730T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant I730T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive are premPS and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign classification, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a benign effect. Overall, the consensus of both general and high‑accuracy predictors points to a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-5.641	Likely Benign	0.404	Ambiguous	Likely Benign	0.18	Likely Benign	0.2	0.12	Likely Benign	0.15	Likely Benign	0.54	Ambiguous	0.103	Likely Benign	-0.83	Neutral	0.995	Probably Damaging	0.934	Probably Damaging	3.49	Benign	0.08	Tolerated			0.1074	0.0885		0	-1	-5.2	-12.05
c.326G>A	S109N 2D AIThe SynGAP1 missense variant S109N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict. High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign 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 Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-5.509	Likely Benign	0.863	Likely Pathogenic	Ambiguous										0.116	Likely Benign	-1.45	Neutral	0.596	Possibly Damaging	0.074	Benign	3.49	Benign	0.00	Affected			0.1350	0.3717		1	1	-2.7	27.03
c.4000A>T	N1334Y 2D AIThe SynGAP1 missense variant N1334Y 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, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, 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 results are unavailable. Overall, the majority of conventional tools predict a pathogenic impact, but the single high‑accuracy benign prediction and the inconclusive consensus suggest uncertainty. Consequently, the variant is most likely pathogenic based on the prevailing evidence, and this assessment does not contradict any ClinVar annotation because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-5.916	Likely Benign	0.770	Likely Pathogenic	Likely Benign										0.249	Likely Benign	-4.62	Deleterious	0.985	Probably Damaging	0.852	Possibly Damaging	3.49	Benign	0.00	Affected			0.0716	0.5447		-2	-2	2.2	49.07
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.424A>G	K142E 2D AIThe SynGAP1 missense variant K142E is not reported in ClinVar (no ClinVar entry) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus (majority vote) 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 predictions point to a pathogenic effect, 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-14.450	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.249	Likely Benign	-2.59	Deleterious	0.247	Benign	0.125	Benign	3.49	Benign	0.00	Affected			0.3644	0.0952		0	1	0.4	0.94
c.428G>C	R143P 2D AIThe SynGAP1 missense variant R143P is listed in ClinVar with an “Uncertain” status (ClinVar ID 4632511) and is present in gnomAD (6‑33432725‑G‑C). 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 (which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this is not in conflict with the ClinVar “Uncertain” classification. 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		0.575842	Disordered	0.538584	Binding	0.338	0.838	0.625					Uncertain		1	6-33432725-G-C	2	1.35e-6	-14.564	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-3.74	Deleterious	0.001	Benign	0.000	Benign	3.49	Benign	0.00	Affected	3.61	5	0.2063	0.4457		-2	0	2.9	-59.07
c.1262C>T	A421V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A421V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) also predicts pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, predicts benign. Rosetta alone is uncertain and is treated as unavailable. Overall, the majority of high‑confidence tools favor a pathogenic effect, so A421V is most likely pathogenic, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000											-8.167	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	-0.05	Likely Benign	0.1	-0.82	Ambiguous	-0.44	Likely Benign	-0.06	Likely Benign	0.111	Likely Benign	-3.15	Deleterious	0.538	Possibly Damaging	0.113	Benign	3.50	Benign	0.14	Tolerated			0.1055	0.3738		0	0	2.4	28.05
c.1270G>A	V424I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V424I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. The only inconclusive results come from FoldX (uncertain) and Foldetta (uncertain). When high‑accuracy methods are considered separately, AlphaMissense‑Optimized predicts benign, the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also predicts benign, while Foldetta remains uncertain. No tool predicts pathogenicity. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-3.814	Likely Benign	0.095	Likely Benign	Likely Benign	-1.04	Ambiguous	0.1	-0.48	Likely Benign	-0.76	Ambiguous	0.02	Likely Benign	0.084	Likely Benign	-0.15	Neutral	0.013	Benign	0.006	Benign	3.50	Benign	0.63	Tolerated			0.0874	0.2609		4	3	0.3	14.03
c.1282T>G	Y428D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y428D is not reported in ClinVar and is absent from gnomAD. Across a broad panel of in silico predictors, 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a deleterious effect, whereas only FATHMM classifies it as benign. 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: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic effect. 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	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-13.473	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.24	Destabilizing	0.0	4.19	Destabilizing	3.72	Destabilizing	1.64	Destabilizing	0.554	Likely Pathogenic	-9.55	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.50	Benign	0.01	Affected			0.4458	0.1003		-4	-3	-2.2	-48.09
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.1426T>A	F476I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F476I has no ClinVar entry and is not reported in gnomAD. Functional prediction tools fall into two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, and FATHMM; pathogenic predictions come from FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive and is treated as unavailable. With seven tools indicating pathogenicity versus five indicating benign, and two high‑accuracy tools supporting pathogenicity, the evidence points to a likely pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no record for this variant. 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											-12.617	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.90	Destabilizing	0.1	3.09	Destabilizing	3.50	Destabilizing	0.39	Likely Benign	0.239	Likely Benign	-1.23	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.50	Benign	0.37	Tolerated			0.1383	0.2202		1	0	1.7	-34.02
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.1675T>G	C559G 2D 3DClick to see structure in 3D Viewer AISynGAP1 C559G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Foldetta, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain calls from Rosetta and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (seven pathogenic vs five benign) and the high‑accuracy consensus lean toward a pathogenic effect. 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	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-12.342	Likely Pathogenic	0.581	Likely Pathogenic	Likely Benign	0.12	Likely Benign	0.1	0.53	Ambiguous	0.33	Likely Benign	0.76	Ambiguous	0.547	Likely Pathogenic	-8.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.50	Benign	0.37	Tolerated			0.2454	0.2001		-3	-3	-2.9	-46.09
c.1912A>G	K638E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638E 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, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are uncertain or unavailable. 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 contains 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	0.098064	Uncertain	0.937	0.260	0.000											-13.390	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.0	1.00	Ambiguous	0.79	Ambiguous	0.32	Likely Benign	0.363	Likely Benign	-3.70	Deleterious	0.995	Probably Damaging	0.947	Probably Damaging	3.50	Benign	0.12	Tolerated			0.3036	0.0790		0	1	0.4	0.94
c.1964T>G	L655R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a benign effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, and the majority of consensus methods (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all score the variant as benign. The only inconclusive result comes from Rosetta, which is treated as unavailable. High‑accuracy assessments reinforce this benign prediction: AlphaMissense‑Optimized reports benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Thus, based on the available predictions, the variant is most likely benign, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000											-4.848	Likely Benign	0.284	Likely Benign	Likely Benign	-0.40	Likely Benign	0.0	0.54	Ambiguous	0.07	Likely Benign	-0.09	Likely Benign	0.160	Likely Benign	0.46	Neutral	0.006	Benign	0.001	Benign	3.50	Benign	0.60	Tolerated			0.1589	0.0615		-3	-2	-8.3	43.03
c.1975T>G	S659A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while ESM1b remains uncertain. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-7.066	In-Between	0.117	Likely Benign	Likely Benign	-0.31	Likely Benign	0.0	0.02	Likely Benign	-0.15	Likely Benign	0.14	Likely Benign	0.088	Likely Benign	-2.22	Neutral	0.097	Benign	0.114	Benign	3.50	Benign	0.64	Tolerated			0.4842	0.3813		1	1	2.6	-16.00
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.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.2006A>C	N669T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy methods give a split verdict: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts it to be pathogenic; Foldetta remains inconclusive. Overall, the majority of tools favor a pathogenic interpretation, and this assessment 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	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-9.875	Likely Pathogenic	0.565	Likely Pathogenic	Likely Benign	0.74	Ambiguous	0.1	0.68	Ambiguous	0.71	Ambiguous	0.49	Likely Benign	0.292	Likely Benign	-5.25	Deleterious	0.991	Probably Damaging	0.962	Probably Damaging	3.50	Benign	0.17	Tolerated			0.1504	0.4803		0	0	2.8	-13.00
c.2020A>C	T674P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T674P missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The high‑accuracy AlphaMissense‑Optimized predicts benign, while Foldetta predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. No other high‑accuracy tool provides a definitive call. Consequently, the evidence is evenly split between benign and pathogenic, leaving the variant’s clinical significance uncertain. This uncertainty does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-8.661	Likely Pathogenic	0.109	Likely Benign	Likely Benign	0.91	Ambiguous	0.6	4.12	Destabilizing	2.52	Destabilizing	0.12	Likely Benign	0.143	Likely Benign	-2.69	Deleterious	0.995	Probably Damaging	0.891	Possibly Damaging	3.50	Benign	0.16	Tolerated			0.2039	0.6103		0	-1	-0.9	-3.99
c.2024A>G	N675S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675S 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, FATHMM, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools (premPS and ESM1b) return uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign consensus; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Taken together, the preponderance of evidence indicates that the variant is most likely benign, 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	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-7.871	In-Between	0.081	Likely Benign	Likely Benign	0.37	Likely Benign	0.0	-0.43	Likely Benign	-0.03	Likely Benign	0.61	Ambiguous	0.157	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.606	Possibly Damaging	3.50	Benign	0.11	Tolerated			0.3462	0.7587		1	1	2.7	-27.03
c.2035T>G	F679V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679V 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, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta provide inconclusive results and are treated as unavailable. Overall, the balance of evidence favors a pathogenic classification, 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	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.868	Likely Pathogenic	0.900	Likely Pathogenic	Ambiguous	1.92	Ambiguous	0.5	0.29	Likely Benign	1.11	Ambiguous	0.89	Ambiguous	0.497	Likely Benign	-6.86	Deleterious	0.993	Probably Damaging	0.968	Probably Damaging	3.50	Benign	0.01	Affected			0.1830	0.2349		-1	-1	1.4	-48.04
c.2036T>C	F679S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining 12 tools (SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the variant as pathogenic. FoldX reports an uncertain outcome and is therefore not counted as evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. 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 (none available). 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											-12.159	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	1.86	Ambiguous	0.4	2.20	Destabilizing	2.03	Destabilizing	1.28	Destabilizing	0.575	Likely Pathogenic	-7.86	Deleterious	0.998	Probably Damaging	0.986	Probably Damaging	3.50	Benign	0.04	Affected			0.4276	0.0200		-3	-2	-3.6	-60.10
c.2081C>G	A694G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-3.420	Likely Benign	0.144	Likely Benign	Likely Benign	0.86	Ambiguous	0.0	1.16	Ambiguous	1.01	Ambiguous	0.86	Ambiguous	0.093	Likely Benign	-1.90	Neutral	0.866	Possibly Damaging	0.171	Benign	3.50	Benign	0.05	Affected			0.2015	0.3387		1	0	-2.2	-14.03
c.2101C>G	P701A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P701A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; all of these classify the substitution as benign. No tool predicts a pathogenic outcome. Predictions that are inconclusive are FoldX (uncertain) and Foldetta (uncertain). High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta remains uncertain. Based on the collective evidence, the variant is most likely benign, 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 Benign	GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000											-6.836	Likely Benign	0.217	Likely Benign	Likely Benign	1.35	Ambiguous	0.0	0.23	Likely Benign	0.79	Ambiguous	-0.16	Likely Benign	0.058	Likely Benign	-0.55	Neutral	0.002	Benign	0.011	Benign	3.50	Benign	0.82	Tolerated			0.3143	0.3765		1	-1	3.4	-26.04
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.2126T>G	L709R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709R 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, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. Tools with uncertain or inconclusive results are Rosetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Overall, the majority of evidence indicates a benign impact for the variant, 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	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-8.636	Likely Pathogenic	0.482	Ambiguous	Likely Benign	0.22	Likely Benign	0.0	0.68	Ambiguous	0.45	Likely Benign	0.62	Ambiguous	0.061	Likely Benign	-1.56	Neutral	0.906	Possibly Damaging	0.314	Benign	3.50	Benign	0.44	Tolerated			0.1127	0.0488		-3	-2	-8.3	43.03
c.4000A>C	N1334H 2D AIThe SynGAP1 missense variant N1334H 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of reliable tools and the high‑accuracy consensus predict a benign impact. 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.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-4.954	Likely Benign	0.496	Ambiguous	Likely Benign										0.164	Likely Benign	-2.99	Deleterious	0.985	Probably Damaging	0.927	Probably Damaging	3.50	Benign	0.00	Affected			0.1963	0.6246		2	1	0.3	23.04
c.4001A>T	N1334I 2D AIThe SynGAP1 missense variant N1334I 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, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the balance of evidence (seven pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-5.880	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-5.06	Deleterious	0.985	Probably Damaging	0.721	Possibly Damaging	3.50	Benign	0.00	Affected			0.0861	0.5491		-2	-3	8.0	-0.94
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.550G>A	E184K 2D AIThe SynGAP1 missense variant E184K 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 majority of computational evidence indicates that E184K 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		0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-14.037	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.289	Likely Benign	-3.31	Deleterious	0.970	Probably Damaging	0.681	Possibly Damaging	3.50	Benign	0.00	Affected			0.2890	0.8227		0	1	-0.4	-0.94
c.556T>A	L186M 2D AIThe SynGAP1 missense variant L186M 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 are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, while 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 predictions (5 pathogenic vs. 3 benign) suggest a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-11.783	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous										0.146	Likely Benign	-1.58	Neutral	0.952	Possibly Damaging	0.694	Possibly Damaging	3.50	Benign	0.00	Affected			0.0671	0.3396		4	2	-1.9	18.03
c.558G>C	L186F 2D AIThe SynGAP1 missense variant L186F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, 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 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 available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500					Uncertain		1				-11.861	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.132	Likely Benign	-3.03	Deleterious	0.009	Benign	0.012	Benign	3.50	Benign	0.00	Affected			0.0524	0.3177		2	0	-1.0	34.02
c.558G>T	L186F 2D AIThe SynGAP1 missense variant L186F has no ClinVar entry (ClinVar status: not reported) and is absent from 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 PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “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 indicates 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.	Likely Pathogenic		0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-11.861	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.132	Likely Benign	-3.03	Deleterious	0.009	Benign	0.012	Benign	3.50	Benign	0.00	Affected			0.0524	0.3177		2	0	-1.0	34.02
c.68A>G	D23G 2D AIThe SynGAP1 missense variant D23G is listed in ClinVar (ID 3644551.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of 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; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” classification but leans toward a benign interpretation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375					Uncertain		1				-2.622	Likely Benign	0.684	Likely Pathogenic	Likely Benign										0.100	Likely Benign	-2.45	Neutral	0.805	Possibly Damaging	0.539	Possibly Damaging	3.50	Benign	0.00	Affected			0.4682	0.7632		1	-1	3.1	-58.04
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.1280A>G	H427R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427R is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438185‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT, while premPS and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign stability change. No predictions or folding results are missing or inconclusive. Overall, the majority of evidence indicates the variant is most likely benign, 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	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000								6-33438185-A-G			-3.259	Likely Benign	0.439	Ambiguous	Likely Benign	-0.04	Likely Benign	0.1	0.48	Likely Benign	0.22	Likely Benign	0.72	Ambiguous	0.168	Likely Benign	-2.61	Deleterious	0.174	Benign	0.018	Benign	3.51	Benign	0.03	Affected	3.38	25	0.2108	0.2121		0	2	-1.3	19.05
c.1309C>G	P437A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P437A 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 REVEL, Rosetta, FATHMM, AlphaMissense‑Optimized, and premPS. Those that predict pathogenicity are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Tools with uncertain or inconclusive results are AlphaMissense‑Default, FoldX, and Foldetta. High‑accuracy assessments give AlphaMissense‑Optimized a benign prediction. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (pathogenic), FATHMM (benign), and PROVEAN (pathogenic), yields a pathogenic consensus. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the balance of evidence leans toward a pathogenic effect for P437A, and this conclusion 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.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-12.059	Likely Pathogenic	0.392	Ambiguous	Likely Benign	1.23	Ambiguous	0.0	-3.14	Stabilizing	-0.96	Ambiguous	0.50	Likely Benign	0.266	Likely Benign	-6.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.51	Benign	0.03	Affected			0.3489	0.4775		1	-1	3.4	-26.04
c.1310C>G	P437R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P437R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, and FATHMM, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. 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 uncertain. With the majority of tools indicating pathogenicity and the high‑accuracy consensus leaning toward pathogenic, the variant is most likely pathogenic. This assessment 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	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.094	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	-3.52	Stabilizing	-1.59	Ambiguous	0.61	Ambiguous	0.461	Likely Benign	-7.72	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.51	Benign	0.03	Affected			0.1448	0.2846		0	-2	-2.9	59.07
c.1327G>A	G443S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the substitution is benign: REVEL, FoldX, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as benign. Only Rosetta and premPS yield uncertain results, which are treated as unavailable. Grouping by consensus, the benign‑predicting tools outnumber any pathogenic calls (none). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. Therefore, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000											-1.258	Likely Benign	0.086	Likely Benign	Likely Benign	0.25	Likely Benign	0.1	-0.72	Ambiguous	-0.24	Likely Benign	-0.65	Ambiguous	0.087	Likely Benign	0.40	Neutral	0.000	Benign	0.001	Benign	3.51	Benign	0.34	Tolerated			0.2409	0.3416		1	0	-0.4	30.03
c.1360A>C	I454L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I454L 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, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic impact. The remaining tools—FoldX, Rosetta, Foldetta, premPS, ESM1b, and AlphaMissense‑Optimized—yield uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward benign, and Foldetta also uncertain. Overall, the majority of reliable predictors and the SGM Consensus favor 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	0.254060	Structured	0.312811	Uncertain	0.965	0.182	0.000											-7.852	In-Between	0.786	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.1	1.36	Ambiguous	0.97	Ambiguous	0.80	Ambiguous	0.246	Likely Benign	-1.98	Neutral	0.908	Possibly Damaging	0.943	Probably Damaging	3.51	Benign	0.26	Tolerated			0.0653	0.2857		2	2	-0.7	0.00
c.1501A>C	I501L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, Rosetta, Foldetta, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. Uncertain or inconclusive results are reported for FoldX, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Benign, all supporting a non‑deleterious effect. Based on the preponderance of benign predictions and the concordant high‑accuracy tools, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-7.348	In-Between	0.282	Likely Benign	Likely Benign	0.78	Ambiguous	0.2	-0.34	Likely Benign	0.22	Likely Benign	0.86	Ambiguous	0.219	Likely Benign	-1.92	Neutral	0.930	Possibly Damaging	0.985	Probably Damaging	3.51	Benign	0.05	Affected			0.0817	0.2261		2	2	-0.7	0.00
c.1644G>C	E548D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548D variant 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, premPS, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict (2 pathogenic, 1 benign, 1 uncertain). Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic effect, 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.		GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-7.359	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.29	Ambiguous	1.02	Ambiguous	0.32	Likely Benign	0.254	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	3.51	Benign	0.09	Tolerated			0.1374	0.2524		3	2	0.0	-14.03
c.1644G>T	E548D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548D variant 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, premPS, SIFT, and FATHMM, whereas a separate group predicts a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict (2 pathogenic, 1 benign, 1 uncertain). Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic impact for E548D, 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	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-7.359	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.29	Ambiguous	1.02	Ambiguous	0.32	Likely Benign	0.254	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	3.51	Benign	0.09	Tolerated			0.1374	0.2524		3	2	0.0	-14.03
c.1918A>G	T640A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN, REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), and SIFT all score the substitution as benign. No tool predicts pathogenicity; only Rosetta yields an uncertain result. High‑accuracy assessments corroborate this benign trend: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Taken together, the evidence overwhelmingly supports a benign classification for T640A, and this conclusion does not contradict any ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-3.068	Likely Benign	0.074	Likely Benign	Likely Benign	0.14	Likely Benign	0.1	0.93	Ambiguous	0.54	Ambiguous	-0.17	Likely Benign	0.078	Likely Benign	0.51	Neutral	0.009	Benign	0.001	Benign	3.51	Benign	0.42	Tolerated			0.3834	0.3202		1	0	2.5	-30.03
c.1931A>C	D644A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D644A 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 REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, Foldetta, and premPS. Only PROVEAN predicts it as pathogenic, while Rosetta and AlphaMissense‑Default are 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 also predicts benign stability. Based on the aggregate evidence, 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	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-3.358	Likely Benign	0.502	Ambiguous	Likely Benign	-0.14	Likely Benign	0.1	-0.83	Ambiguous	-0.49	Likely Benign	-0.18	Likely Benign	0.274	Likely Benign	-3.90	Deleterious	0.311	Benign	0.032	Benign	3.51	Benign	0.39	Tolerated			0.3883	0.5481		0	-2	5.3	-44.01
c.2167A>G	T723A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess sequence conservation, structural impact, or functional effect all converge on a benign outcome: SIFT, PolyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, REVEL, and the protein‑stability predictors FoldX, Rosetta, premPS, and Foldetta all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Based on the uniform predictions, the variant is most likely benign, 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.	Likely Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-4.572	Likely Benign	0.064	Likely Benign	Likely Benign	-0.47	Likely Benign	0.0	0.16	Likely Benign	-0.16	Likely Benign	0.25	Likely Benign	0.053	Likely Benign	-0.91	Neutral	0.161	Benign	0.045	Benign	3.51	Benign	0.06	Tolerated			0.3902	0.3639		1	0	2.5	-30.03
c.2168C>G	T723R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify it as benign. Two tools (polyPhen‑2 HumDiv and HumVar) predict it to be pathogenic, while FoldX, Foldetta, and AlphaMissense‑Default are uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign impact for T723R, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-3.654	Likely Benign	0.408	Ambiguous	Likely Benign	-0.90	Ambiguous	0.1	-0.13	Likely Benign	-0.52	Ambiguous	0.44	Likely Benign	0.146	Likely Benign	-1.50	Neutral	0.931	Possibly Damaging	0.458	Possibly Damaging	3.51	Benign	0.29	Tolerated			0.0794	0.2437		-1	-1	-3.8	55.08
c.2187C>A	N729K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729K has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus call (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. Tools with uncertain or mixed results are Foldetta (protein‑folding stability) and Rosetta. High‑accuracy assessments: AlphaMissense‑Optimized reports a benign effect; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign; Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not contradict the current ClinVar status, which contains no report for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625											-5.101	Likely Benign	0.648	Likely Pathogenic	Likely Benign	-0.03	Likely Benign	0.1	1.92	Ambiguous	0.95	Ambiguous	0.12	Likely Benign	0.036	Likely Benign	-1.39	Neutral	0.109	Benign	0.033	Benign	3.51	Benign	0.47	Tolerated			0.1948	0.3612		1	0	-0.4	14.07
c.2187C>G	N729K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729K has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus call (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. Tools with uncertain or mixed results are Foldetta (protein‑folding stability) and Rosetta. High‑accuracy assessments: AlphaMissense‑Optimized reports a benign effect; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign; Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not contradict the current ClinVar status, which contains no report for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625											-5.101	Likely Benign	0.648	Likely Pathogenic	Likely Benign	-0.03	Likely Benign	0.1	1.92	Ambiguous	0.95	Ambiguous	0.12	Likely Benign	0.036	Likely Benign	-1.39	Neutral	0.109	Benign	0.033	Benign	3.51	Benign	0.47	Tolerated			0.1948	0.3612		1	0	-0.4	14.07
c.325A>G	S109G 2D AIThe SynGAP1 missense variant S109G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates Likely Benign. 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 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 Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-3.918	Likely Benign	0.549	Ambiguous	Likely Benign										0.132	Likely Benign	-1.95	Neutral	0.378	Benign	0.067	Benign	3.51	Benign	0.00	Affected			0.2686	0.3779		1	0	0.4	-30.03
c.427C>G	R143G 2D AIThe SynGAP1 missense variant R143G is not reported in ClinVar and is absent from gnomAD. In silico predictors that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Predictors that agree on a pathogenic effect include PROVEAN, 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 impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from multiple independent tools points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar annotation exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.575842	Disordered	0.538584	Binding	0.338	0.838	0.625											-12.686	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.151	Likely Benign	-3.86	Deleterious	0.319	Benign	0.124	Benign	3.51	Benign	0.00	Affected			0.3502	0.3547		-3	-2	4.1	-99.14
c.557T>C	L186S 2D AIThe SynGAP1 missense variant L186S 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 (majority vote). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a deleterious effect, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels 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 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		0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-13.906	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.250	Likely Benign	-4.73	Deleterious	0.952	Possibly Damaging	0.601	Possibly Damaging	3.51	Benign	0.00	Affected			0.3214	0.0808		-3	-2	-4.6	-26.08
c.1281T>A	H427Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H427Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, 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 SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect for H427Q. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-5.858	Likely Benign	0.367	Ambiguous	Likely Benign	0.77	Ambiguous	0.1	0.62	Ambiguous	0.70	Ambiguous	0.73	Ambiguous	0.142	Likely Benign	-2.41	Neutral	0.864	Possibly Damaging	0.088	Benign	3.52	Benign	0.02	Affected			0.1556	0.3382		3	0	-0.3	-9.01
c.1281T>G	H427Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 H427Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, 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 SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect for H427Q. This conclusion is consistent with the absence of a ClinVar classification, 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	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-5.858	Likely Benign	0.367	Ambiguous	Likely Benign	0.77	Ambiguous	0.1	0.62	Ambiguous	0.70	Ambiguous	0.73	Ambiguous	0.142	Likely Benign	-2.41	Neutral	0.864	Possibly Damaging	0.088	Benign	3.52	Benign	0.02	Affected			0.1556	0.3382		3	0	-0.3	-9.01
c.1373C>G	T458R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T458R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, and FATHMM, whereas a larger set—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. Uncertain results come from FoldX and premPS. 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) as benign. Overall, the majority of evidence points to a pathogenic effect, 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	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-12.984	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	-0.81	Ambiguous	0.1	-0.11	Likely Benign	-0.46	Likely Benign	0.61	Ambiguous	0.390	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.52	Benign	0.20	Tolerated			0.1016	0.3013		-1	-1	-3.8	55.08
c.1501A>G	I501V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions from FoldX, Rosetta, and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for I501V, 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	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-2.326	Likely Benign	0.083	Likely Benign	Likely Benign	0.94	Ambiguous	0.0	0.56	Ambiguous	0.75	Ambiguous	0.06	Likely Benign	0.200	Likely Benign	0.20	Neutral	0.951	Possibly Damaging	0.960	Probably Damaging	3.52	Benign	1.00	Tolerated			0.0985	0.2491		4	3	-0.3	-14.03
c.1771G>T	A591S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect, and the Foldetta stability analysis is inconclusive (unavailable). Consequently, the variant is most likely benign based on the available 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 Benign	GAP	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000											-7.535	In-Between	0.126	Likely Benign	Likely Benign	0.58	Ambiguous	0.1	1.21	Ambiguous	0.90	Ambiguous	0.49	Likely Benign	0.083	Likely Benign	-2.11	Neutral	0.034	Benign	0.082	Benign	3.52	Benign	0.19	Tolerated			0.2405	0.3304		1	1	-2.6	16.00
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.1913A>C	K638T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638T is not reported in ClinVar and is absent from gnomAD. Consensus from standard in silico predictors shows a split: benign calls come from REVEL, Rosetta, premPS, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; FoldX and Foldetta are inconclusive. High‑accuracy assessments give AlphaMissense‑Optimized a benign score, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence favors a pathogenic effect for K638T. This prediction 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	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-8.856	Likely Pathogenic	0.775	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.0	0.23	Likely Benign	0.55	Ambiguous	0.07	Likely Benign	0.404	Likely Benign	-5.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.52	Benign	0.03	Affected			0.1632	0.2619		0	-1	3.2	-27.07
c.1940G>T	G647V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess sequence conservation and structural impact uniformly classify the substitution as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a tolerated change. No tool predicts pathogenicity; only FoldX and Rosetta report uncertain stability effects, which are treated as unavailable evidence. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a benign effect. Therefore, 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.	Likely Benign	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000											-4.713	Likely Benign	0.126	Likely Benign	Likely Benign	0.85	Ambiguous	0.1	-0.59	Ambiguous	0.13	Likely Benign	-0.13	Likely Benign	0.115	Likely Benign	-1.77	Neutral	0.178	Benign	0.073	Benign	3.52	Benign	0.12	Tolerated			0.1318	0.3946		-1	-3	4.6	42.08
c.1970G>C	W657S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657S 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 (SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta) predict a pathogenic impact; Rosetta remains uncertain. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic, 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 pathogenic. Based on the collective evidence, the variant 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	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-11.817	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	2.27	Destabilizing	0.2	1.87	Ambiguous	2.07	Destabilizing	1.26	Destabilizing	0.334	Likely Benign	-11.82	Deleterious	0.999	Probably Damaging	0.947	Probably Damaging	3.52	Benign	0.09	Tolerated			0.4299	0.0489		-2	-3	0.1	-99.14
c.1970G>T	W657L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant W657L is listed in ClinVar with an uncertain significance (ClinVar ID 2767440.0) and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta predicts a benign folding‑stability change. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the ClinVar uncertain status but leans toward pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000					Uncertain		1				-14.411	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.14	Likely Benign	0.1	0.73	Ambiguous	0.44	Likely Benign	0.87	Ambiguous	0.213	Likely Benign	-10.86	Deleterious	0.277	Benign	0.078	Benign	3.52	Benign	0.14	Tolerated	3.39	24	0.2302	0.2049		-2	-2	4.7	-73.05
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.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.1984C>G	Q662E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662E 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 SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. High‑accuracy methods all support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta is benign. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, 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	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-12.750	Likely Pathogenic	0.191	Likely Benign	Likely Benign	0.32	Likely Benign	0.0	0.64	Ambiguous	0.48	Likely Benign	0.24	Likely Benign	0.083	Likely Benign	-1.25	Neutral	0.876	Possibly Damaging	0.147	Benign	3.52	Benign	0.27	Tolerated			0.1660	0.1823		2	2	0.0	0.98
c.2006A>G	N669S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669S is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33441265‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. 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 (combining FoldX‑MD and Rosetta) is also inconclusive. No folding‑stability metrics (FoldX, Rosetta, Foldetta) provide definitive evidence. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, 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.		GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000								6-33441265-A-G	3	1.86e-6	-8.369	Likely Pathogenic	0.187	Likely Benign	Likely Benign	0.55	Ambiguous	0.1	1.88	Ambiguous	1.22	Ambiguous	0.35	Likely Benign	0.210	Likely Benign	-4.02	Deleterious	0.999	Probably Damaging	0.960	Probably Damaging	3.52	Benign	0.14	Tolerated	3.39	27	0.3521	0.4480		1	1	2.7	-27.03
c.2027G>C	S676T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and Rosetta. No tool predicts a pathogenic outcome; the only inconclusive results are from FoldX (Uncertain) and Foldetta (Uncertain). High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta remains Uncertain. Overall, the consensus of available 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.	Likely Benign	GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-5.621	Likely Benign	0.092	Likely Benign	Likely Benign	0.79	Ambiguous	0.1	0.34	Likely Benign	0.57	Ambiguous	-0.36	Likely Benign	0.098	Likely Benign	0.91	Neutral	0.050	Benign	0.017	Benign	3.52	Benign	1.00	Tolerated			0.1575	0.6286		1	1	0.1	14.03
c.2119G>A	A707T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A707T is reported in gnomAD (ID 6‑33441584‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. The Foldetta stability prediction is inconclusive and therefore not considered evidence. Overall, the consensus of available predictions indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000								6-33441584-G-A	1	6.20e-7	-0.836	Likely Benign	0.175	Likely Benign	Likely Benign	0.50	Ambiguous	0.0	2.36	Destabilizing	1.43	Ambiguous	0.10	Likely Benign	0.252	Likely Benign	-0.57	Neutral	0.980	Probably Damaging	0.947	Probably Damaging	3.52	Benign	0.44	Tolerated	3.50	9	0.0880	0.4330		0	1	-2.5	30.03
c.2126T>A	L709Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Thus, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-5.758	Likely Benign	0.179	Likely Benign	Likely Benign	0.13	Likely Benign	0.0	0.40	Likely Benign	0.27	Likely Benign	0.18	Likely Benign	0.033	Likely Benign	-0.78	Neutral	0.998	Probably Damaging	0.923	Probably Damaging	3.52	Benign	0.48	Tolerated			0.0838	0.0488		-2	-2	-7.3	14.97
c.398T>C	L133P 2D AIThe SynGAP1 missense variant L133P 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 REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), yields a pathogenic consensus. Foldetta, a protein‑folding stability method, 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 existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-7.744	In-Between	0.982	Likely Pathogenic	Likely Pathogenic										0.342	Likely Benign	-3.16	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.52	Benign	0.00	Affected			0.3270	0.1048		-3	-3	-5.4	-16.04
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.418T>C	S140P 2D AIThe SynGAP1 missense variant S140P 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, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates 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. High‑accuracy tools specifically show AlphaMissense‑Optimized as pathogenic, while SGM Consensus and Foldetta are unavailable. Overall, the majority of evidence points to a pathogenic impact for S140P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-4.089	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-2.59	Deleterious	0.995	Probably Damaging	0.979	Probably Damaging	3.52	Benign	0.08	Tolerated			0.1726	0.5117		1	-1	-0.8	10.04
c.428G>T	R143L 2D AIThe SynGAP1 missense variant R143L is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33432725‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic; the Foldetta stability analysis is unavailable. 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		0.575842	Disordered	0.538584	Binding	0.338	0.838	0.625								6-33432725-G-T	1	6.77e-7	-14.250	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.316	Likely Benign	-4.37	Deleterious	0.319	Benign	0.124	Benign	3.52	Benign	0.00	Affected	3.61	5	0.1758	0.4886		-2	-3	8.3	-43.03
c.552G>C	E184D 2D AIThe SynGAP1 E184D 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, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) 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.			0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-6.753	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-2.55	Deleterious	0.930	Possibly Damaging	0.584	Possibly Damaging	3.52	Benign	0.00	Affected			0.2249	0.5394		3	2	0.0	-14.03
c.552G>T	E184D 2D AIThe SynGAP1 E184D 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, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) 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.			0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-6.753	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-2.55	Deleterious	0.930	Possibly Damaging	0.584	Possibly Damaging	3.52	Benign	0.00	Affected			0.2249	0.5394		3	2	0.0	-14.03
c.67G>A	D23N 2D AIThe SynGAP1 D23N missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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 Benign		0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-3.918	Likely Benign	0.719	Likely Pathogenic	Likely Benign										0.077	Likely Benign	-1.88	Neutral	0.805	Possibly Damaging	0.539	Possibly Damaging	3.52	Benign	0.00	Affected			0.2236	0.8784		2	1	0.0	-0.98
c.68A>C	D23A 2D AIThe SynGAP1 D23A 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, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic versus four benign) suggest a pathogenic impact. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-2.732	Likely Benign	0.777	Likely Pathogenic	Likely Benign										0.112	Likely Benign	-2.57	Deleterious	0.909	Possibly Damaging	0.539	Possibly Damaging	3.52	Benign	0.00	Affected			0.4613	0.8203		0	-2	5.3	-44.01
c.1252A>G	K418E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418E 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, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evaluated tools (seven 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 for K418E. 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											-12.443	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.80	Ambiguous	0.72	Ambiguous	0.47	Likely Benign	0.367	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.53	Benign	0.07	Tolerated			0.3578	0.0471		0	1	0.4	0.94