Data | SynGAP Server

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
			Domain	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.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													MD Alert	Verdict	Description
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.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.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.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.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.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.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.2047A>T	I683F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, while AlphaMissense‑Optimized and Foldetta are inconclusive and thus treated as unavailable evidence. Overall, the balance of evidence favors a pathogenic classification for I683F, and this assessment does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-12.781	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous	1.38	Ambiguous	0.1	-0.23	Likely Benign	0.58	Ambiguous	0.59	Ambiguous	0.481	Likely Benign	-3.99	Deleterious	0.971	Probably Damaging	0.499	Possibly Damaging	3.27	Benign	0.01	Affected			0.0770	0.2307		1	0	-1.7	34.02
c.2048T>A	I683N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683N is not reported in ClinVar and is absent from gnomAD. Functional 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 the pathogenic signal: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) also indicates pathogenicity. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, 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 Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-12.120	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.18	Destabilizing	0.1	2.08	Destabilizing	2.13	Destabilizing	1.46	Destabilizing	0.546	Likely Pathogenic	-6.87	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	3.26	Benign	0.01	Affected			0.0978	0.1133		-2	-3	-8.0	0.94
c.2048T>C	I683T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683T has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools predict pathogenicity: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support this pattern: AlphaMissense‑Optimized classifies the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic; the Foldetta stability analysis is inconclusive and therefore unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for I683T. This conclusion does not contradict ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-9.891	Likely Pathogenic	0.775	Likely Pathogenic	Likely Benign	1.67	Ambiguous	0.1	1.35	Ambiguous	1.51	Ambiguous	1.25	Destabilizing	0.548	Likely Pathogenic	-4.77	Deleterious	0.999	Probably Damaging	0.981	Probably Damaging	3.29	Benign	0.08	Tolerated			0.1090	0.0880		0	-1	-5.2	-12.05
c.2048T>G	I683S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. No prediction or folding stability result is missing or inconclusive; all available evidence points to a deleterious effect. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-11.443	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	2.53	Destabilizing	0.2	1.94	Ambiguous	2.24	Destabilizing	1.35	Destabilizing	0.552	Likely Pathogenic	-5.88	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.29	Benign	0.05	Affected			0.1936	0.1320		-1	-2	-5.3	-26.08
c.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.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.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>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.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.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.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.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.2054T>C	L685S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685S is 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, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any existing 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	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-12.303	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.08	Destabilizing	0.2	2.95	Destabilizing	3.02	Destabilizing	1.24	Destabilizing	0.520	Likely Pathogenic	-5.99	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.27	Benign	0.01	Affected			0.2844	0.0505		-3	-2	-4.6	-26.08
c.2054T>G	L685W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685W 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, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain results and are not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, 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	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-15.885	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.53	Ambiguous	0.2	1.14	Ambiguous	1.34	Ambiguous	1.14	Destabilizing	0.509	Likely Pathogenic	-5.99	Deleterious	1.000	Probably Damaging	0.984	Probably Damaging	3.23	Benign	0.00	Affected			0.0700	0.2328		-2	-2	-4.7	73.05
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.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.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>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.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.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.2059C>G	R687G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R687G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta indicates a destabilizing, pathogenic effect. AlphaMissense‑Optimized is uncertain and therefore treated as unavailable. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, 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	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-12.900	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	2.94	Destabilizing	0.3	2.53	Destabilizing	2.74	Destabilizing	1.27	Destabilizing	0.360	Likely Benign	-6.26	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.88	Benign	0.01	Affected			0.2508	0.2119		-3	-2	4.1	-99.14
c.2060G>A	R687Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687Q is annotated in ClinVar as benign (ClinVar ID 2693600.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, SGM‑Consensus indicating pathogenicity, and Foldetta (integrating FoldX‑MD and Rosetta outputs) classifying it as benign. With three high‑accuracy tools giving benign or uncertain results and only one (SGM‑Consensus) suggesting pathogenicity, the overall evidence leans toward a benign effect. This prediction aligns with the ClinVar benign classification, indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000					Likely Benign		1				-10.002	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.92	Ambiguous	0.1	-0.37	Likely Benign	0.28	Likely Benign	1.55	Destabilizing	0.401	Likely Benign	-3.37	Deleterious	1.000	Probably Damaging	0.844	Possibly Damaging	3.91	Benign	0.03	Affected	3.42	17	0.2143	0.1952		1	1	1.0	-28.06
c.2060G>C	R687P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R687P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas the remaining eleven tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—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, and PROVEAN) reports a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no conflicting ClinVar annotation, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-15.697	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.31	Destabilizing	0.3	6.63	Destabilizing	4.47	Destabilizing	0.89	Ambiguous	0.553	Likely Pathogenic	-6.12	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.87	Benign	0.01	Affected			0.1811	0.3159		0	-2	2.9	-59.07
c.2062G>A	E688K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, FoldX, FATHMM, and Foldetta, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by Rosetta and premPS. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the majority of conventional predictors and the SGM Consensus lean toward pathogenicity, and there is no conflict with ClinVar status because the variant is not yet catalogued. Thus, based on current 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	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-15.177	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.6	-0.60	Ambiguous	-0.08	Likely Benign	0.77	Ambiguous	0.469	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.975	Probably Damaging	3.27	Benign	0.01	Affected			0.2458	0.5518		0	1	-0.4	-0.94
c.2062G>C	E688Q 2D AIThe SynGAP1 missense variant E688Q is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools (premPS and AlphaMissense‑Optimized) give uncertain results and are treated as unavailable. High‑accuracy assessments further show SGM‑Consensus 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, with no ClinVar annotation 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.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-9.419	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.9	0.15	Likely Benign	0.16	Likely Benign	0.59	Ambiguous	0.302	Likely Benign	-2.53	Deleterious	0.997	Probably Damaging	0.973	Probably Damaging	3.27	Benign	0.15	Tolerated			0.1154	0.5387		2	2	0.0	-0.98
c.2063A>C	E688A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Foldetta, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX, Rosetta, and premPS are inconclusive. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of evidence points to a pathogenic effect for E688A. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-13.556	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.5	-0.53	Ambiguous	0.01	Likely Benign	0.68	Ambiguous	0.495	Likely Benign	-5.55	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.01	Affected			0.3806	0.5296		0	-1	5.3	-58.04
c.2063A>G	E688G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E688G has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive predictions come from Foldetta, premPS, and Rosetta. 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). Overall, the majority of reliable tools predict a deleterious effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-14.338	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.17	Destabilizing	0.5	1.44	Ambiguous	1.81	Ambiguous	0.86	Ambiguous	0.486	Likely Benign	-6.55	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.27	Benign	0.00	Affected			0.3059	0.4433		0	-2	3.1	-72.06
c.2063A>T	E688V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E688V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Foldetta, premPS, and FATHMM, while pathogenic calls are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. High‑accuracy methods give divergent results: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of tools support a pathogenic effect, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-14.642	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-0.02	Likely Benign	0.6	-0.63	Ambiguous	-0.33	Likely Benign	0.37	Likely Benign	0.532	Likely Pathogenic	-6.62	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.19	Benign	0.02	Affected			0.0681	0.5831		-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.2065C>G	L689V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) and the SGM Consensus (Likely Pathogenic) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM Consensus is Likely Pathogenic; Foldetta predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for L689V. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-11.387	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	2.98	Destabilizing	0.1	2.25	Destabilizing	2.62	Destabilizing	1.32	Destabilizing	0.234	Likely Benign	-2.97	Deleterious	0.926	Possibly Damaging	0.481	Possibly Damaging	3.27	Benign	0.00	Affected			0.1393	0.3189		2	1	0.4	-14.03
c.2065C>T	L689F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Two tools (Rosetta and premPS) yield uncertain results. High‑accuracy assessments further support pathogenicity: 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 preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-9.817	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	2.45	Destabilizing	0.2	1.95	Ambiguous	2.20	Destabilizing	0.67	Ambiguous	0.286	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.860	Possibly Damaging	3.18	Benign	0.00	Affected			0.0608	0.2891		2	0	-1.0	34.02
c.2066T>A	L689H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689H 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 further support this: 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 agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-14.659	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.40	Destabilizing	0.1	2.50	Destabilizing	2.95	Destabilizing	2.21	Destabilizing	0.532	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.14	Benign	0.00	Affected			0.1013	0.0456		-2	-3	-7.0	23.98
c.2066T>C	L689P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689P 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 no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-17.900	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.76	Destabilizing	0.2	13.35	Destabilizing	10.06	Destabilizing	2.29	Destabilizing	0.631	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.17	Benign	0.00	Affected			0.3668	0.1353		-3	-3	-5.4	-16.04
c.2066T>G	L689R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689R 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 (both HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, 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 Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-17.776	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.91	Destabilizing	0.6	5.61	Destabilizing	5.76	Destabilizing	2.14	Destabilizing	0.609	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.932	Probably Damaging	3.15	Benign	0.00	Affected			0.1208	0.0530		-3	-2	-8.3	43.03
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.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.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>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.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.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.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.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.2074C>G	L692V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as pathogenic, and Foldetta also predicts pathogenic. No predictions are missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-11.441	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	3.29	Destabilizing	0.1	2.91	Destabilizing	3.10	Destabilizing	1.57	Destabilizing	0.286	Likely Benign	-2.99	Deleterious	0.978	Probably Damaging	0.606	Possibly Damaging	3.12	Benign	0.01	Affected			0.1395	0.2460		2	1	0.4	-14.03
c.2075T>A	L692Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692Q is listed in ClinVar as Pathogenic (ClinVar ID 2714634.0) 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, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this conclusion aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000					Pathogenic		1				-13.873	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.24	Destabilizing	0.1	3.27	Destabilizing	3.26	Destabilizing	2.76	Destabilizing	0.596	Likely Pathogenic	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.06	Benign	0.00	Affected	3.42	17	0.1079	0.0488		-2	-2	-7.3	14.97
c.2075T>C	L692P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692P is listed in ClinVar with an “Uncertain” status (ClinVar ID 847082.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the remaining tools (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 assessments further support this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000					Uncertain		1				-16.447	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	9.19	Destabilizing	0.1	13.20	Destabilizing	11.20	Destabilizing	1.69	Destabilizing	0.668	Likely Pathogenic	-6.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.06	Benign	0.00	Affected	3.42	17	0.3642	0.1025		-3	-3	-5.4	-16.04	186.2	62.8	-0.2	0.1	-0.7	0.3	X							Potentially Pathogenic	The isobutyl side chain of Leu692, located in the middle of an α-helix (res. Leu685-Gln702), engages in hydrophobic packing with nearby residues (e.g., Leu441, Leu431, Leu696) in the inter-helix space. Prolines lack a free amide group necessary for hydrogen bonding with the carbonyl group of Glu688 in the same manner as Leu692 in the WT. Consequently, the residue swap with proline disrupts the continuity of the secondary structure element in the variant simulations. Additionally, the side chain of Pro692 is not as optimal as Leu692 for hydrophobic packing in the inter-helix space.
c.2075T>G	L692R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692R 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. No prediction or folding 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 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	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-16.656	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.34	Destabilizing	0.0	5.51	Destabilizing	4.93	Destabilizing	1.96	Destabilizing	0.611	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.07	Benign	0.00	Affected			0.1204	0.0488		-3	-2	-8.3	43.03
c.2077C>A	H693N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693N 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—premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—label it pathogenic. 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. Overall, the preponderance of evidence points to a pathogenic effect for H693N, 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	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-12.275	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.1	0.80	Ambiguous	1.27	Ambiguous	1.28	Destabilizing	0.436	Likely Benign	-6.98	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.10	Benign	0.01	Affected			0.1380	0.1849		2	1	-0.3	-23.04
c.2077C>G	H693D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity largely agree: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No predictions are missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-15.500	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.60	Destabilizing	0.1	2.03	Destabilizing	2.32	Destabilizing	1.62	Destabilizing	0.578	Likely Pathogenic	-8.97	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	3.09	Benign	0.01	Affected			0.2166	0.1108		1	-1	-0.3	-22.05
c.2078A>C	H693P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693P 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 variant 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 folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-16.281	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	5.54	Destabilizing	0.2	6.09	Destabilizing	5.82	Destabilizing	1.06	Destabilizing	0.600	Likely Pathogenic	-9.97	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.09	Benign	0.01	Affected			0.2080	0.3210		0	-2	1.6	-40.02
c.2078A>G	H693R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of algorithms (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect, and Foldetta’s stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-14.326	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.39	Ambiguous	0.2	1.28	Ambiguous	1.34	Ambiguous	1.03	Destabilizing	0.593	Likely Pathogenic	-7.97	Deleterious	0.998	Probably Damaging	0.646	Possibly Damaging	3.13	Benign	0.01	Affected			0.1839	0.1670		2	0	-1.3	19.05
c.2078A>T	H693L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H693L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from Foldetta, premPS, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results are reported by FoldX and Rosetta. High‑accuracy assessments indicate AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also leans pathogenic, whereas Foldetta predicts benign stability. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-14.006	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	-0.53	Ambiguous	0.1	0.92	Ambiguous	0.20	Likely Benign	-0.29	Likely Benign	0.573	Likely Pathogenic	-10.96	Deleterious	0.979	Probably Damaging	0.390	Benign	3.18	Benign	0.01	Affected			0.0824	0.4675		-2	-3	7.0	-23.98
c.2079T>A	H693Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, while the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented predictors and the high‑accuracy consensus indicates that H693Q is most likely pathogenic, a conclusion that aligns with the lack of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-11.425	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	0.78	Ambiguous	0.85	Ambiguous	1.27	Destabilizing	0.386	Likely Benign	-7.97	Deleterious	1.000	Probably Damaging	0.921	Probably Damaging	3.14	Benign	0.01	Affected			0.1274	0.2955		3	0	-0.3	-9.01
c.2079T>G	H693Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, while the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented predictors and the high‑accuracy consensus indicates that H693Q is most likely pathogenic, a conclusion that aligns with the lack of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-11.425	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	0.78	Ambiguous	0.85	Ambiguous	1.27	Destabilizing	0.386	Likely Benign	-7.97	Deleterious	1.000	Probably Damaging	0.921	Probably Damaging	3.14	Benign	0.01	Affected			0.1274	0.2955		3	0	-0.3	-9.01
c.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.2084T>A	L695Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact comprise REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta provide uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus, derived from a majority of high‑confidence predictors, indicates pathogenicity; Foldetta remains inconclusive. Overall, the majority of reliable tools predict a pathogenic effect, and this is consistent with the lack of ClinVar annotation (no contradiction). 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	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-12.192	Likely Pathogenic	0.706	Likely Pathogenic	Likely Benign	1.88	Ambiguous	0.1	2.03	Destabilizing	1.96	Ambiguous	1.71	Destabilizing	0.554	Likely Pathogenic	-5.92	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.17	Benign	0.08	Tolerated			0.0869	0.0688		-2	-2	-7.3	14.97
c.2084T>C	L695P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695P is 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, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts 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 these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-17.496	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.63	Destabilizing	0.2	4.73	Destabilizing	4.68	Destabilizing	2.11	Destabilizing	0.612	Likely Pathogenic	-6.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.16	Benign	0.00	Affected			0.3044	0.0992		-3	-3	-5.4	-16.04
c.2084T>G	L695R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695R 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 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the variant as pathogenic. AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also pathogenic. Overall, the evidence overwhelmingly indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-15.582	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	2.05	Destabilizing	0.1	2.66	Destabilizing	2.36	Destabilizing	1.57	Destabilizing	0.605	Likely Pathogenic	-5.92	Deleterious	0.993	Probably Damaging	0.588	Possibly Damaging	3.17	Benign	0.00	Affected			0.1220	0.0530		-3	-2	-8.3	43.03
c.2086C>G	L696V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696V variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) report a pathogenic outcome; Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for the variant, 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	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000					Uncertain		1				-11.909	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	2.35	Destabilizing	0.1	1.85	Ambiguous	2.10	Destabilizing	1.46	Destabilizing	0.351	Likely Benign	-2.79	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected	3.46	13	0.1307	0.2830		1	2	0.4	-14.03
c.2086C>T	L696F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L696F has no ClinVar entry and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, and FATHMM. Those that predict a pathogenic effect are 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 likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. 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	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-9.651	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	0.14	Likely Benign	0.1	0.74	Ambiguous	0.44	Likely Benign	0.55	Ambiguous	0.422	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.05	Benign	0.00	Affected			0.0667	0.2008		2	0	-1.0	34.02
c.2087T>A	L696H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L696H is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: all available predictors except FATHMM classify the variant as pathogenic (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). Only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Taken together, the overwhelming majority of computational evidence supports a pathogenic classification, 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	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-17.042	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.56	Destabilizing	0.0	2.55	Destabilizing	2.56	Destabilizing	2.07	Destabilizing	0.569	Likely Pathogenic	-6.58	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.00	Benign	0.00	Affected			0.1009	0.0488		-2	-3	-7.0	23.98
c.2087T>C	L696P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L696P is listed in ClinVar as Pathogenic (ClinVar ID 1699350.0) 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, and AlphaMissense‑Optimized—report it as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a destabilizing, pathogenic outcome. Taken together, the overwhelming majority of predictions and the high‑accuracy tools classify the variant as pathogenic, fully consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000					Likely Pathogenic		1				-16.926	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.66	Destabilizing	0.2	10.84	Destabilizing	8.75	Destabilizing	2.13	Destabilizing	0.678	Likely Pathogenic	-6.58	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.00	Benign	0.00	Affected	3.46	13	0.3065	0.1995		-3	-3	-5.4	-16.04	180.6	65.9	0.1	0.0	-0.6	0.1	X							Potentially Pathogenic	The isobutyl side chain of Leu696, located in the middle of an α-helix (res. Leu685-Gln702), engages in hydrophobic packing with nearby residues (e.g., Leu441, Leu431, Leu692, Leu714) in the inter-helix space. Prolines lack a free amide group necessary for hydrogen bonding with the carbonyl group of Leu692 in the same manner as Leu696 in the WT. Consequently, the residue swap with proline disrupts the continuity of the secondary structure element in the variant simulations. Additionally, the side chain of Pro696 is not as optimal as Leu696 for hydrophobic packing in the inter-helix space.
c.2087T>G	L696R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L696R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: all available predictors except FATHMM (which flags it as benign) report pathogenicity. The benign group contains only FATHMM; the pathogenic group includes SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 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 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	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-19.609	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.67	Destabilizing	0.0	5.36	Destabilizing	4.52	Destabilizing	2.44	Destabilizing	0.624	Likely Pathogenic	-5.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.01	Benign	0.00	Affected			0.1200	0.0688		-3	-2	-8.3	43.03
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.2090G>T	W697L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. No predictions are missing or inconclusive. Overall, the majority of tools (seven pathogenic vs. six benign) lean toward a pathogenic interpretation, and this does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-9.057	Likely Pathogenic	0.676	Likely Pathogenic	Likely Benign	0.20	Likely Benign	0.1	-0.17	Likely Benign	0.02	Likely Benign	0.90	Ambiguous	0.280	Likely Benign	-8.48	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	3.58	Benign	0.02	Affected			0.2222	0.2848		-2	-2	4.7	-73.05
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.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.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.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.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.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.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.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.2107C>T	L703F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta remains unavailable. Overall, the majority of reliable predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.929	Likely Pathogenic	0.768	Likely Pathogenic	Likely Benign	1.03	Ambiguous	0.1	0.59	Ambiguous	0.81	Ambiguous	0.50	Likely Benign	0.247	Likely Benign	-3.25	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.12	Benign	0.00	Affected			0.0600	0.2555		2	0	-1.0	34.02
c.2108T>A	L703H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM‑Consensus itself is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts Pathogenic. Taken together, the overwhelming majority of evidence indicates that 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	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-12.886	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	2.52	Destabilizing	0.0	2.29	Destabilizing	2.41	Destabilizing	1.75	Destabilizing	0.420	Likely Benign	-5.71	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.09	Benign	0.00	Affected			0.1038	0.0288		-2	-3	-7.0	23.98
c.2108T>C	L703P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703P 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 variant as pathogenic, while only FATHMM predicts it benign. The SGM‑Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” result (3 pathogenic vs. 1 benign). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus is likely pathogenic; and Foldetta, integrating 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	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-13.766	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	4.44	Destabilizing	0.1	9.38	Destabilizing	6.91	Destabilizing	1.54	Destabilizing	0.559	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.11	Benign	0.00	Affected			0.3698	0.1186		-3	-3	-5.4	-16.04
c.2108T>G	L703R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) all classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. The preponderance of pathogenic predictions, together with the high‑accuracy tools’ positive results, suggests that L703R is most likely pathogenic. 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	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-13.244	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	2.85	Destabilizing	0.0	3.74	Destabilizing	3.30	Destabilizing	1.79	Destabilizing	0.459	Likely Benign	-4.92	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.13	Benign	0.00	Affected			0.1223	0.0488		-3	-2	-8.3	43.03
c.2110A>C	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in gnomAD and has no ClinVar entry. 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, 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. FoldX, Rosetta, and Foldetta provide uncertain stability results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as 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	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.178	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
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.2112C>A	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM, while 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, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus confirms Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result, providing no additional evidence. Overall, the preponderance of evidence from multiple independent predictors indicates that S704R 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	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.200	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
c.2112C>G	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is 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: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). FoldX and Rosetta give uncertain results, and Foldetta (a combined FoldX‑MD/Rosetta stability assessment) is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.200	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
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.2114A>T	K705M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705M 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 (3/4 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact, 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	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.595	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	-0.13	Likely Benign	0.0	0.53	Ambiguous	0.20	Likely Benign	0.17	Likely Benign	0.306	Likely Benign	-3.65	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.26	Benign	0.00	Affected			0.0724	0.3057		0	-1	5.8	3.02
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.2117A>T	E706V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E706V 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 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Two tools, FoldX and Foldetta, give uncertain or inconclusive results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta remains uncertain. Overall, the majority of predictions lean toward a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000											-9.306	Likely Pathogenic	0.667	Likely Pathogenic	Likely Benign	1.05	Ambiguous	0.0	0.30	Likely Benign	0.68	Ambiguous	0.05	Likely Benign	0.099	Likely Benign	-2.63	Deleterious	0.555	Possibly Damaging	0.109	Benign	4.07	Benign	0.16	Tolerated			0.0528	0.4275		-2	-2	7.7	-29.98
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.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>A	L708H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708H is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default; the SGM Consensus score is also labeled Likely Pathogenic. Stability‑based methods FoldX and Rosetta return uncertain results, and Foldetta likewise is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of conventional predictors lean toward pathogenicity, whereas a few high‑accuracy tools suggest benign or are inconclusive. Thus, the variant is most likely pathogenic based on the prevailing predictions, 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	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-8.059	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.84	Ambiguous	0.1	1.55	Ambiguous	1.70	Ambiguous	1.44	Destabilizing	0.243	Likely Benign	-4.68	Deleterious	1.000	Probably Damaging	0.981	Probably Damaging	3.25	Benign	0.02	Affected			0.0824	0.0288		-2	-3	-7.0	23.98
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.2123T>G	L708R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708R 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 effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as Likely Pathogenic. FoldX, Rosetta, 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 (six pathogenic vs. four benign) and the SGM Consensus support a pathogenic classification, whereas AlphaMissense‑Optimized suggests benign. The variant is most likely pathogenic based on the collective predictions, 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	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-9.154	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.0	0.90	Ambiguous	0.89	Ambiguous	1.24	Destabilizing	0.249	Likely Benign	-4.18	Deleterious	0.988	Probably Damaging	0.598	Possibly Damaging	3.27	Benign	0.19	Tolerated			0.1091	0.0488		-3	-2	-8.3	43.03
c.2128A>G	K710E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K710E missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-11.405	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.0	0.94	Ambiguous	0.75	Ambiguous	0.39	Likely Benign	0.178	Likely Benign	-3.53	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.45	Benign	0.08	Tolerated			0.2655	0.0789		0	1	0.4	0.94
c.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.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.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.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.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.2132T>C	L711P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L711P 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; all other evaluated algorithms—including 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, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the overwhelming agreement among these tools, 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											-12.128	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.70	Destabilizing	0.1	8.15	Destabilizing	6.93	Destabilizing	2.09	Destabilizing	0.375	Likely Benign	-6.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.28	Benign	0.00	Affected			0.3300	0.0986		-3	-3	-5.4	-16.04
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.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.2135G>A	G712D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G712D is catalogued in gnomAD (ID 6‑33441600‑G‑A) but has no ClinVar entry. In silico predictors show mixed results: benign calls come from REVEL, SIFT, and FATHMM, while pathogenic calls are made by FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain predictions are reported by premPS and AlphaMissense‑Optimized. The high‑accuracy consensus tools give a pathogenic verdict: AlphaMissense‑Optimized is inconclusive, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Overall, the majority of reliable predictors and the consensus methods lean toward a pathogenic effect, and this assessment does not conflict with ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000								6-33441600-G-A	1	6.20e-7	-8.211	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.87	Destabilizing	0.1	5.37	Destabilizing	4.12	Destabilizing	0.90	Ambiguous	0.320	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.67	Benign	0.12	Tolerated	3.50	9	0.2146	0.2533		-1	1	-3.1	58.04
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.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.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>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.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.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.2141T>A	L714Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L714Q is not reported in ClinVar (ClinVar: not reported) and is absent from gnomAD (gnomAD: not found). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated tools—including FoldX, Rosetta, Foldetta, premPS, 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 of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-12.145	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.91	Destabilizing	0.0	5.23	Destabilizing	4.07	Destabilizing	2.13	Destabilizing	0.378	Likely Benign	-5.56	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.11	Benign	0.00	Affected			0.1096	0.0558		-2	-2	-7.3	14.97
c.2141T>C	L714P 2D AIThe SynGAP1 missense variant L714P 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 remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores 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 classifies the variant as pathogenic. Based on the preponderance of evidence from these tools, 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	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-12.562	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	7.48	Destabilizing	1.9	13.54	Destabilizing	10.51	Destabilizing	2.26	Destabilizing	0.441	Likely Benign	-6.44	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.08	Benign	0.00	Affected			0.3572	0.1253		-3	-3	-5.4	-16.04
c.2141T>G	L714R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L714R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No prediction or folding stability result is 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 available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-12.763	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.38	Destabilizing	0.2	7.54	Destabilizing	5.96	Destabilizing	2.09	Destabilizing	0.402	Likely Benign	-5.62	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.09	Benign	0.00	Affected			0.1186	0.0558		-3	-2	-8.3	43.03
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.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.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.2144C>G	P715R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715R 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 (SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Because the pathogenic predictions outnumber the benign ones and the high‑accuracy consensus supports a deleterious effect, the variant is most likely pathogenic. This assessment does not contradict 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	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-12.191	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	2.19	Destabilizing	0.1	0.53	Ambiguous	1.36	Ambiguous	0.87	Ambiguous	0.324	Likely Benign	-8.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.01	Affected			0.1389	0.2620		0	-2	-2.9	59.07
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.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.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.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.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.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.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.2150T>C	L717P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) all classify the variant as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-10.214	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.96	Destabilizing	0.2	6.56	Destabilizing	5.26	Destabilizing	1.66	Destabilizing	0.447	Likely Benign	-5.32	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.28	Benign	0.00	Affected			0.3065	0.1053		-3	-3	-5.4	-16.04
c.2150T>G	L717R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717R is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the majority‑vote SGM Consensus) predict pathogenicity; FoldX is uncertain. High‑accuracy methods reinforce a pathogenic verdict: AlphaMissense‑Optimized scores it as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. No prediction is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-11.352	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.1	3.78	Destabilizing	2.72	Destabilizing	1.57	Destabilizing	0.353	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.28	Benign	0.00	Affected			0.1169	0.0558		-3	-2	-8.3	43.03
c.2152C>A	L718I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718I is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools (Foldetta, premPS, Rosetta) give uncertain results and are not considered evidence. High‑accuracy methods specifically show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Because the majority of reliable predictors (eight out of eleven) indicate pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-10.560	Likely Pathogenic	0.615	Likely Pathogenic	Likely Benign	2.21	Destabilizing	0.2	1.37	Ambiguous	1.79	Ambiguous	0.89	Ambiguous	0.296	Likely Benign	-1.90	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.37	Pathogenic	0.00	Affected			0.0876	0.3206		2	2	0.7	0.00
c.2152C>G	L718V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized reports benign, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, 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	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.585	Likely Pathogenic	0.693	Likely Pathogenic	Likely Benign	3.15	Destabilizing	0.1	2.11	Destabilizing	2.63	Destabilizing	1.14	Destabilizing	0.237	Likely Benign	-2.83	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.00	Affected			0.1485	0.2656		2	1	0.4	-14.03
c.2152C>T	L718F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718F lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools cluster into two groups: benign predictions are made only by REVEL, whereas the remaining tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity; premPS is uncertain and is not counted as evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the overwhelming consensus of these predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.302	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	3.87	Destabilizing	0.2	2.64	Destabilizing	3.26	Destabilizing	0.78	Ambiguous	0.347	Likely Benign	-3.73	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0590	0.2979		2	0	-1.0	34.02
c.2153T>A	L718H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718H is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No predictions are inconclusive or missing. 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	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-14.923	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.84	Destabilizing	0.1	2.68	Destabilizing	3.26	Destabilizing	2.69	Destabilizing	0.460	Likely Benign	-6.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1020	0.0526		-2	-3	-7.0	23.98
c.2153T>C	L718P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect, so the benign‑prediction group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Consequently, 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	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-15.643	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	6.56	Destabilizing	0.1	9.69	Destabilizing	8.13	Destabilizing	2.35	Destabilizing	0.660	Likely Pathogenic	-6.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.3854	0.1221		-3	-3	-5.4	-16.04
c.2153T>G	L718R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, 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, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-16.119	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.90	Destabilizing	0.2	5.05	Destabilizing	5.48	Destabilizing	2.57	Destabilizing	0.484	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1254	0.0600		-3	-2	-8.3	43.03
c.2158G>A	D720N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D720N is listed in ClinVar as benign (ClinVar ID 2837618.0) and is present in gnomAD (ID 6‑33441623‑G‑A). Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus as pathogenic. With seven pathogenic versus six benign predictions overall, the variant is most likely pathogenic according to in‑silico evidence, which contradicts the benign classification in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125					Likely Benign		1	6-33441623-G-A	5	3.10e-6	-9.135	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	0.01	Likely Benign	0.0	-0.20	Likely Benign	-0.10	Likely Benign	0.46	Likely Benign	0.289	Likely Benign	-3.74	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	2.18	Pathogenic	0.01	Affected	3.50	9	0.1216	0.5513		1	2	0.0	-0.98
c.2158G>C	D720H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720H missense variant is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and is labeled Likely Pathogenic. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, indicates a Benign effect. Considering the overall distribution of 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	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-12.355	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	-0.87	Ambiguous	-0.42	Likely Benign	0.48	Likely Benign	0.444	Likely Benign	-5.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.13	Pathogenic	0.01	Affected			0.1363	0.6198		1	-1	0.3	22.05
c.2158G>T	D720Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D720Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and premPS, while pathogenic predictions are made by SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. The high‑accuracy consensus (SGM Consensus) classifies the variant as Likely Pathogenic, and Foldetta likewise yields an uncertain stability change. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment 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	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-14.771	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	-0.74	Ambiguous	0.1	-1.38	Ambiguous	-1.06	Ambiguous	0.20	Likely Benign	0.499	Likely Benign	-7.05	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.0626	0.5973		-4	-3	2.2	48.09
c.2159A>C	D720A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and SIFT, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, whereas Foldetta (combining FoldX‑MD and Rosetta) predicts a benign impact, and AlphaMissense‑Optimized remains uncertain. Overall, the predictions are split, with a slight tilt toward pathogenicity from the consensus and high‑accuracy methods. Thus, the variant is most likely pathogenic based on the available predictions, and this does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-10.999	Likely Pathogenic	0.871	Likely Pathogenic	Ambiguous	-0.14	Likely Benign	0.0	-0.35	Likely Benign	-0.25	Likely Benign	0.40	Likely Benign	0.424	Likely Benign	-6.20	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.16	Pathogenic	0.11	Tolerated			0.3726	0.5551		0	-2	5.3	-44.01
c.2159A>G	D720G 2D AISynGAP1 missense variant D720G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Foldetta, and premPS, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools remain inconclusive: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-11.130	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.4	0.53	Ambiguous	0.49	Likely Benign	0.46	Likely Benign	0.427	Likely Benign	-5.67	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.15	Pathogenic	0.01	Affected			0.4027	0.5011		1	-1	3.1	-58.04
c.2159A>T	D720V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D720V has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Foldetta, and premPS, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-12.730	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.0	-0.78	Ambiguous	-0.35	Likely Benign	0.20	Likely Benign	0.437	Likely Benign	-7.18	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	2.12	Pathogenic	0.00	Affected			0.0822	0.5708		-2	-3	7.7	-15.96
c.2161A>T	I721F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact, while premPS remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming agreement among these 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	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-12.559	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	4.61	Destabilizing	0.1	2.74	Destabilizing	3.68	Destabilizing	0.66	Ambiguous	0.295	Likely Benign	-3.74	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.0420	0.2931		1	0	-1.7	34.02
c.2162T>A	I721N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; 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 calculations, also predicts pathogenicity. Based on the collective evidence, 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.	Likely Pathogenic	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-14.905	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.82	Destabilizing	0.0	3.21	Destabilizing	3.02	Destabilizing	2.10	Destabilizing	0.425	Likely Benign	-6.30	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.19	Pathogenic	0.00	Affected			0.0737	0.0340		-2	-3	-8.0	0.94
c.2162T>C	I721T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721T is not reported in ClinVar (ClinVar status: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that indicate a benign effect include only REVEL. All other evaluated tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote) yields Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts Pathogenic. No prediction or folding result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-10.374	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.73	Destabilizing	0.0	2.56	Destabilizing	2.65	Destabilizing	2.11	Destabilizing	0.417	Likely Benign	-4.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.0918	0.1019		0	-1	-5.2	-12.05
c.2162T>G	I721S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports 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 predictions are missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125					Uncertain		1				-14.032	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	3.91	Destabilizing	0.1	3.96	Destabilizing	3.94	Destabilizing	2.28	Destabilizing	0.466	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.21	Pathogenic	0.00	Affected	3.50	9	0.2606	0.1110		-1	-2	-5.3	-26.08	203.3	49.3	-0.1	0.0	-1.1	0.0							X	Uncertain	The sec-butyl side chain of Ile721, located on an α-helix (res. Leu714-Arg726), engages in hydrophobic packing with other residues in the hydrophobic inter-helix space, such as Phe420, Tyr417, His693, and Leu717. In the variant simulations, the hydroxyl side chain of Ser721 forms hydrogen bonds with nearby residues, such as Leu717 and His693. Although no major structural changes are observed during the variant simulations, the hydrophilic residue Ser721 could disrupt the hydrophobic packing during folding. However, because the model ends abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2163C>G	I721M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant I721M is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, Rosetta, and PROVEAN, whereas pathogenic predictions are made by SGM‑Consensus, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Tools with inconclusive results 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 pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable predictors indicate a pathogenic effect, which aligns with the ClinVar designation of uncertain significance rather than contradicting it. Therefore, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125					Uncertain		1				-9.767	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous	0.71	Ambiguous	0.0	0.45	Likely Benign	0.58	Ambiguous	1.00	Destabilizing	0.225	Likely Benign	-2.40	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.0576	0.2726		2	1	-2.6	18.03
c.2164A>C	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools and the high‑accuracy methods lean toward a pathogenic effect. Thus, the variant is most likely pathogenic based on current predictions, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.306	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.2164A>G	S722G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722G is not reported in ClinVar and is present in gnomAD (ID 6‑33441629‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and the protein‑folding stability method Foldetta. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as benign. No evidence from the high‑accuracy tools contradicts the benign predictions, but the consensus and several individual pathogenic predictors suggest a potential deleterious impact. Based on the overall pattern of predictions, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and the presence of multiple pathogenic signals. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375								6-33441629-A-G	2	1.24e-6	-9.141	Likely Pathogenic	0.214	Likely Benign	Likely Benign	0.24	Likely Benign	0.1	0.67	Ambiguous	0.46	Likely Benign	0.50	Likely Benign	0.270	Likely Benign	-2.72	Deleterious	0.998	Probably Damaging	0.863	Possibly Damaging	2.49	Pathogenic	0.14	Tolerated	3.50	8	0.2202	0.3400		0	1	0.4	-30.03
c.2164A>T	S722C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. 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 benign. Overall, the majority of individual predictors and the high‑accuracy methods lean toward a benign impact, with only the SGM Consensus suggesting pathogenicity. Thus, the variant is most likely benign based on the available predictions, 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	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-8.060	Likely Pathogenic	0.273	Likely Benign	Likely Benign	0.22	Likely Benign	0.0	-0.23	Likely Benign	-0.01	Likely Benign	0.28	Likely Benign	0.362	Likely Benign	-3.44	Deleterious	1.000	Probably Damaging	0.968	Probably Damaging	2.46	Pathogenic	0.05	Affected			0.1132	0.4306		0	-1	3.3	16.06
c.2165G>T	S722I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S722I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, premPS, SIFT, and the folding‑stability method Foldetta, whereas pathogenic predictions are reported by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are provided by AlphaMissense‑Optimized, FoldX, and Rosetta. High‑accuracy analyses further clarify the picture: AlphaMissense‑Optimized remains inconclusive; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign impact on protein stability. Overall, the majority of evidence leans toward a pathogenic interpretation, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-11.165	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.69	Ambiguous	0.1	-0.65	Ambiguous	0.02	Likely Benign	0.18	Likely Benign	0.232	Likely Benign	-3.88	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.48	Pathogenic	0.07	Tolerated			0.0776	0.4187		-1	-2	5.3	26.08
c.2166C>A	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.221	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.2166C>G	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, based on the current computational predictions, the S722R variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.220	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.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.2170G>A	A724T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A724T missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include REVEL, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Predictions that are inconclusive are AlphaMissense‑Default, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) suggest a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, as there is no existing classification to contradict. 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	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-8.047	Likely Pathogenic	0.456	Ambiguous	Likely Benign	0.95	Ambiguous	0.1	1.10	Ambiguous	1.03	Ambiguous	0.40	Likely Benign	0.273	Likely Benign	-2.87	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	2.09	Pathogenic	0.01	Affected			0.1149	0.5897		1	0	-2.5	30.03
c.2170G>C	A724P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A724P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: REVEL predicts a benign effect, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS [uncertain], PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized returns a pathogenic score; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, classifies the variant as pathogenic. No tool suggests a benign outcome, and the single benign prediction (REVEL) is outweighed by the consensus of pathogenic predictions. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this mutation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-12.817	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.3	6.35	Destabilizing	4.63	Destabilizing	0.52	Ambiguous	0.391	Likely Benign	-3.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.04	Pathogenic	0.04	Affected			0.1642	0.4273		1	-1	-3.4	26.04
c.2171C>A	A724D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724D is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Four methods (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for A724D, 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	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-12.233	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	0.2	0.86	Ambiguous	0.96	Ambiguous	0.60	Ambiguous	0.335	Likely Benign	-4.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1596	0.1812		0	-2	-5.3	44.01
c.2171C>G	A724G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall distribution 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	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-8.908	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	1.45	Ambiguous	0.1	1.73	Ambiguous	1.59	Ambiguous	0.56	Ambiguous	0.286	Likely Benign	-3.10	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.07	Pathogenic	0.08	Tolerated			0.2001	0.3609		1	0	-2.2	-14.03
c.2171C>T	A724V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A724V missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign, SGM Consensus predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. With no ClinVar annotation, there is no contradiction between the predictions and existing clinical data. Overall, the evidence is mixed, but the majority of high‑confidence tools lean toward a benign effect, suggesting the variant is most likely benign rather than pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-9.000	Likely Pathogenic	0.471	Ambiguous	Likely Benign	0.42	Likely Benign	0.1	0.35	Likely Benign	0.39	Likely Benign	0.24	Likely Benign	0.241	Likely Benign	-3.28	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	2.07	Pathogenic	0.01	Affected			0.0872	0.5620		0	0	2.4	28.05
c.2173C>G	L725V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The remaining methods (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta provides no definitive stability change. 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		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-8.291	Likely Pathogenic	0.461	Ambiguous	Likely Benign	1.76	Ambiguous	0.1	1.87	Ambiguous	1.82	Ambiguous	0.77	Ambiguous	0.183	Likely Benign	-2.69	Deleterious	0.993	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.01	Affected			0.1739	0.3977		2	1	0.4	-14.03
c.2174T>A	L725Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. The majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, Rosetta, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain or inconclusive results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, 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		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-13.952	Likely Pathogenic	0.888	Likely Pathogenic	Ambiguous	1.55	Ambiguous	0.1	2.09	Destabilizing	1.82	Ambiguous	1.88	Destabilizing	0.319	Likely Benign	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1198	0.1203		-2	-2	-7.3	14.97
c.2174T>C	L725P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—FoldX, Rosetta, Foldetta, 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)—classify the variant as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) 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 collective predictions, 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		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-15.390	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	4.91	Destabilizing	0.1	9.02	Destabilizing	6.97	Destabilizing	1.82	Destabilizing	0.396	Likely Benign	-6.08	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.3796	0.1664		-3	-3	-5.4	-16.04
c.2174T>G	L725R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, Rosetta, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. FoldX and Foldetta report uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, while Foldetta remains uncertain. Based on the overwhelming majority of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-15.383	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.3	2.16	Destabilizing	1.43	Ambiguous	1.49	Destabilizing	0.345	Likely Benign	-5.46	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1374	0.0846		-3	-2	-8.3	43.03
c.2176A>T	R726W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726W has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of tools (seven) predict a benign effect, but the SGM‑Consensus and several high‑accuracy methods indicate pathogenicity, leaving the variant’s clinical significance uncertain. The predictions do not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-10.091	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	0.46	Likely Benign	0.1	0.46	Likely Benign	0.46	Likely Benign	0.15	Likely Benign	0.217	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.57	Benign	0.01	Affected			0.1161	0.4252		2	-3	3.6	30.03
c.2179A>G	N727D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N727D has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default, while the SGM‑Consensus score is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward a benign effect, and this does not contradict any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-5.640	Likely Benign	0.601	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.0	0.35	Likely Benign	0.29	Likely Benign	0.36	Likely Benign	0.142	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.18	Pathogenic	0.08	Tolerated			0.1899	0.4309		2	1	0.0	0.98
c.2179A>T	N727Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727Y has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Two tools remain inconclusive: AlphaMissense‑Default and Rosetta. Separately, the high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of individual predictors and the SGM Consensus lean toward a pathogenic interpretation, while the high‑accuracy folding‑stability assessment is benign. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.106	Likely Pathogenic	0.426	Ambiguous	Likely Benign	-0.12	Likely Benign	0.1	-0.52	Ambiguous	-0.32	Likely Benign	0.35	Likely Benign	0.347	Likely Benign	-5.34	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.12	Pathogenic	0.02	Affected			0.0563	0.6091		-2	-2	2.2	49.07
c.2180A>T	N727I 2D 3DClick to see structure in 3D Viewer AISynGAP1 N727I is not reported in ClinVar and is absent from gnomAD. Benign predictions come from REVEL, FoldX, premPS, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta provide inconclusive results. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts likely pathogenic, and Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.230	Likely Pathogenic	0.577	Likely Pathogenic	Likely Benign	0.17	Likely Benign	0.1	0.90	Ambiguous	0.54	Ambiguous	0.43	Likely Benign	0.319	Likely Benign	-5.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.13	Pathogenic	0.03	Affected			0.0666	0.5917		-2	-3	8.0	-0.94
c.2181C>A	N727K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N727K is catalogued in gnomAD (ID 6‑33441646‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, SIFT, and the protein‑folding stability method Foldetta; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the consensus score SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM Consensus indicates likely pathogenic, and Foldetta reports benign stability. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625								6-33441646-C-A	1	6.19e-7	-10.601	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	-0.12	Likely Benign	0.2	-0.44	Likely Benign	-0.28	Likely Benign	0.86	Ambiguous	0.148	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.12	Tolerated	3.59	7	0.2002	0.5590		0	1	-0.4	14.07
c.2181C>G	N727K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence (seven pathogenic vs. five benign, with two uncertain) points to a pathogenic impact. This conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-10.601	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	-0.12	Likely Benign	0.2	-0.44	Likely Benign	-0.28	Likely Benign	0.86	Ambiguous	0.148	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.12	Tolerated	3.59	7	0.2002	0.5590		0	1	-0.4	14.07
c.2182C>A	P728T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728T has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, while the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) 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, 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 P728T, 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		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-9.605	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	1.06	Ambiguous	0.0	1.27	Ambiguous	1.17	Ambiguous	0.62	Ambiguous	0.298	Likely Benign	-6.21	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1843	0.3917		0	-1	0.9	3.99
c.2182C>G	P728A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728A 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, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the preponderance of evidence from multiple in silico tools 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		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-9.350	Likely Pathogenic	0.800	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.1	0.79	Ambiguous	0.79	Ambiguous	0.69	Ambiguous	0.277	Likely Benign	-6.59	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.3568	0.3148		1	-1	3.4	-26.04
c.2182C>T	P728S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P728S is not reported in ClinVar and is present in gnomAD (ID 6‑33441647‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, whereas the majority of tools predict pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results from FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy consensus methods give a Likely Pathogenic verdict from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and an Uncertain outcome from AlphaMissense‑Optimized; Foldetta also reports Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P728S, 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		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625								6-33441647-C-T	1	6.20e-7	-9.047	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	0.89	Ambiguous	0.0	0.98	Ambiguous	0.94	Ambiguous	0.54	Ambiguous	0.280	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected	3.59	7	0.3571	0.3571		-1	1	0.8	-10.04
c.2183C>A	P728H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which predict a deleterious impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic effect for P728H, 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.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-8.897	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.94	Ambiguous	0.0	0.86	Ambiguous	0.90	Ambiguous	0.64	Ambiguous	0.402	Likely Benign	-7.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1993	0.3016		0	-2	-1.6	40.02
c.2183C>G	P728R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FoldX, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further indicate a likely pathogenic status from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and an uncertain outcome from Foldetta (combining FoldX‑MD and Rosetta). AlphaMissense‑Optimized also remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-10.309	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.59	Ambiguous	0.52	Ambiguous	0.70	Ambiguous	0.418	Likely Benign	-7.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1728	0.2865		0	-2	-2.9	59.07
c.2183C>T	P728L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect for P728L. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-11.125	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.0	0.15	Likely Benign	0.47	Likely Benign	0.20	Likely Benign	0.402	Likely Benign	-8.27	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.2321	0.4713		-3	-3	5.4	16.04
c.2248G>T	G750W 2D AIThe SynGAP1 missense variant G750W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, while the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the variant as damaging. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that G750W is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.618285	Disordered	0.646832	Binding	0.348	0.866	0.625											-8.433	Likely Pathogenic	0.427	Ambiguous	Likely Benign										0.135	Likely Benign	-3.30	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.0738	0.4009		-7	-2	-0.5	129.16
c.2255C>G	S752W 2D AIThe SynGAP1 missense variant S752W is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, and this conclusion is not contradicted by ClinVar status (which is absent). Thus, the variant is most likely pathogenic based on the collective evidence, despite the single benign prediction from AlphaMissense‑Optimized. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.690594	Binding	0.365	0.877	0.625											-6.771	Likely Benign	0.565	Likely Pathogenic	Likely Benign										0.341	Likely Benign	-3.54	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	1.49	Pathogenic	0.00	Affected			0.0837	0.6241		-2	-3	-0.1	99.14
c.2281C>T	R761W 2D AIThe SynGAP1 missense variant R761W is listed in gnomAD (ID 6‑33441746‑C‑T) 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 impact are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of tools (six pathogenic vs. four benign) suggest a pathogenic effect, and this conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250								6-33441746-C-T	1	6.20e-7	-9.248	Likely Pathogenic	0.665	Likely Pathogenic	Likely Benign										0.193	Likely Benign	-3.52	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	2.66	Benign	0.06	Tolerated	3.99	5	0.1018	0.3668		-3	2	3.6	30.03
c.2284G>C	D762H 2D AIThe SynGAP1 D762H 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 and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance 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		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-4.643	Likely Benign	0.909	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-2.73	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.08	Pathogenic	0.02	Affected			0.2007	0.9102		1	-1	0.3	22.05
c.2284G>T	D762Y 2D AIThe SynGAP1 D762Y 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 and ESM1b, whereas a larger group predicts a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; Foldetta (a protein‑folding stability approach combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-6.959	Likely Benign	0.905	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-3.24	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.07	Pathogenic	0.01	Affected			0.0700	0.7929		-4	-3	2.2	48.09
c.2285A>G	D762G 2D AIThe SynGAP1 missense variant D762G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the majority of predictions and the SGM‑Consensus outcome, 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		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-1.062	Likely Benign	0.812	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.55	Deleterious	0.998	Probably Damaging	0.949	Probably Damaging	2.10	Pathogenic	0.08	Tolerated			0.4710	0.7841		1	-1	3.1	-58.04
c.2297C>A	S766Y 2D AIThe SynGAP1 missense variant S766Y is reported in gnomAD (ID 6‑33442455‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) predicts pathogenic, and no Foldetta stability data are available. 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		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250								6-33442455-C-A			-8.636	Likely Pathogenic	0.641	Likely Pathogenic	Likely Benign										0.222	Likely Benign	-2.67	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	4.09	Benign	0.00	Affected	3.64	6	0.0794	0.5609		-2	-3	-0.5	76.10
c.2297C>T	S766F 2D AIThe SynGAP1 missense variant S766F is listed in gnomAD (ID 6‑33442455‑C‑T) but has no ClinVar entry. Functional prediction tools show a split verdict: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250								6-33442455-C-T			-8.944	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign										0.233	Likely Benign	-2.87	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	4.08	Benign	0.00	Affected	3.64	6	0.0770	0.5887		-2	-3	3.6	60.10
c.2302G>T	D768Y 2D AIThe SynGAP1 missense variant D768Y is listed in ClinVar with status “Uncertain” (ClinVar ID 1061652.0) and is present in gnomAD (variant ID 6‑33442460‑G‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, 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 “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar designation of uncertainty. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250					Uncertain		1	6-33442460-G-T			-9.866	Likely Pathogenic	0.824	Likely Pathogenic	Ambiguous										0.234	Likely Benign	-2.86	Deleterious	0.989	Probably Damaging	0.806	Possibly Damaging	4.01	Benign	0.07	Tolerated	3.64	6	0.0581	0.7525		-4	-3	2.2	48.09
c.2303A>T	D768V 2D AIThe SynGAP1 D768V variant 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 pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic; 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		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-9.528	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.164	Likely Benign	-2.62	Deleterious	0.611	Possibly Damaging	0.140	Benign	4.04	Benign	0.02	Affected			0.0802	0.8019		-2	-3	7.7	-15.96
c.2344G>C	D782H 2D AIThe SynGAP1 missense variant D782H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only REVEL predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta data are unavailable. Taken together, the majority of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar assertion. 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		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.528	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous										0.311	Likely Benign	-2.63	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1333	0.7286		1	-1	0.3	22.05
c.2344G>T	D782Y 2D AIThe SynGAP1 missense variant D782Y is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while only REVEL predicts a benign outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of 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		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.785	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous										0.382	Likely Benign	-3.75	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0559	0.6202		-4	-3	2.2	48.09
c.2345A>C	D782A 2D AIThe SynGAP1 missense variant D782A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. Uncertain predictions come from ESM1b and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, reports the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain and Foldetta results are unavailable. Taken together, the preponderance of evidence from multiple in silico predictors and the SGM‑Consensus suggests that D782A is most likely pathogenic. 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		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-7.054	In-Between	0.892	Likely Pathogenic	Ambiguous										0.345	Likely Benign	-3.33	Deleterious	0.990	Probably Damaging	0.932	Probably Damaging	1.95	Pathogenic	0.01	Affected			0.3819	0.6121		0	-2	5.3	-44.01
c.2345A>G	D782G 2D AIThe SynGAP1 missense variant D782G 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 ESM1b, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-6.811	Likely Benign	0.858	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.27	Deleterious	0.995	Probably Damaging	0.950	Probably Damaging	1.95	Pathogenic	0.02	Affected			0.3816	0.6318		1	-1	3.1	-58.04
c.2345A>T	D782V 2D AIThe SynGAP1 missense variant D782V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which reports “Likely Pathogenic”). The high‑accuracy AlphaMissense‑Optimized tool yields an uncertain result, and the Foldetta stability assessment is unavailable. Overall, the consensus of the available predictions strongly favors a pathogenic effect for D782V. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.250	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.462	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.979	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.0803	0.6477		-2	-3	7.7	-15.96
c.2353C>A	R785S 2D AIThe SynGAP1 missense variant R785S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-2.926	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-2.93	Deleterious	0.980	Probably Damaging	0.765	Possibly Damaging	2.34	Pathogenic	0.01	Affected			0.3523	0.3800		0	-1	3.7	-69.11
c.2353C>G	R785G 2D AIThe SynGAP1 missense variant R785G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further reveal that AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus again suggests pathogenicity; Foldetta stability analysis is not available for this variant. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the SGM‑Consensus result. Because the variant is not present in ClinVar, there is no existing clinical classification to contradict; 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	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-3.684	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-3.44	Deleterious	0.980	Probably Damaging	0.818	Possibly Damaging	2.25	Pathogenic	0.00	Affected			0.3695	0.3686		-3	-2	4.1	-99.14
c.2353C>T	R785C 2D AIThe SynGAP1 R785C missense variant is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442905‑C‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points toward a pathogenic impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625					Uncertain		1	6-33442905-C-T	29	1.80e-5	-5.887	Likely Benign	0.662	Likely Pathogenic	Likely Benign										0.126	Likely Benign	-5.06	Deleterious	0.144	Benign	0.046	Benign	2.22	Pathogenic	0.00	Affected	3.64	6	0.3775	0.3530		-4	-3	7.0	-53.05
c.2354G>C	R785P 2D AIThe SynGAP1 missense variant R785P is catalogued in gnomAD (6‑33442906‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the balance of evidence, with seven pathogenic versus three benign predictions and a pathogenic consensus from SGM, indicates that R785P is most likely pathogenic. This conclusion does not contradict ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625								6-33442906-G-C			-3.603	Likely Benign	0.721	Likely Pathogenic	Likely Benign										0.203	Likely Benign	-4.12	Deleterious	0.998	Probably Damaging	0.958	Probably Damaging	2.24	Pathogenic	0.01	Affected	3.64	6	0.2370	0.4485		-2	0	2.9	-59.07
c.2354G>T	R785L 2D AIThe SynGAP1 missense variant R785L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. 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 results are unavailable. Overall, the balance of evidence leans toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-4.457	Likely Benign	0.699	Likely Pathogenic	Likely Benign										0.158	Likely Benign	-4.43	Deleterious	0.960	Probably Damaging	0.627	Possibly Damaging	2.26	Pathogenic	0.01	Affected			0.1993	0.4539		-3	-2	8.3	-43.03
c.2356C>T	L786F 2D AIThe SynGAP1 missense variant L786F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. 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 results are unavailable. Overall, the balance of evidence leans toward pathogenicity, 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	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.949	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.112	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.00	Affected			0.0765	0.3847		2	0	-1.0	34.02
c.2357T>A	L786H 2D AIThe SynGAP1 missense variant L786H is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. Grouping by agreement, two tools predict benign, seven predict pathogenic, and AlphaMissense‑Optimized remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion 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	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-5.892	Likely Benign	0.836	Likely Pathogenic	Ambiguous										0.168	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1309	0.1214		-2	-3	-7.0	23.98
c.2357T>C	L786P 2D AISynGAP1 missense variant L786P is reported in gnomAD (ID 6‑33442909‑T‑C) but has no ClinVar entry. Functional prediction tools show discordant results: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized reports a benign effect, SGM‑Consensus confirms a likely pathogenic outcome, and Foldetta results are unavailable. Overall, the majority of conventional tools and the SGM‑Consensus support a pathogenic interpretation, while one high‑accuracy tool suggests benign. No ClinVar status is present, 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	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750								6-33442909-T-C			-3.217	Likely Benign	0.656	Likely Pathogenic	Likely Benign										0.219	Likely Benign	-4.06	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.00	Affected	3.77	5	0.3343	0.1814		-3	-3	-5.4	-16.04
c.2357T>G	L786R 2D AIThe SynGAP1 missense variant L786R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, and the lack of a Foldetta result does not alter this conclusion. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.989	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.169	Likely Benign	-3.07	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1403	0.1288		-3	-2	-8.3	43.03
c.2359C>A	P787T 2D AISynGAP1 missense variant P787T is listed in ClinVar as benign (ClinVar ID 862728.0) and is present in gnomAD (6‑33442911‑C‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions are made by AlphaMissense‑Default, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized result is benign, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, which contradicts the ClinVar benign classification. Thus, the variant is most likely pathogenic, contradicting the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750					Likely Benign		1	6-33442911-C-A	17	1.05e-5	-4.813	Likely Benign	0.603	Likely Pathogenic	Likely Benign										0.258	Likely Benign	-4.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.46	Pathogenic	0.01	Affected	3.64	6	0.1577	0.5629		0	-1	0.9	3.99
c.2360C>A	P787H 2D AIThe SynGAP1 missense variant P787H has no ClinVar entry and is not listed in gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—predict it to be pathogenic. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic” (3 pathogenic votes versus 1 benign). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of predictions lean toward pathogenicity, but this is contradicted by the benign call from AlphaMissense‑Optimized. Because ClinVar has no reported status, there is no conflict with existing clinical annotations. Thus, the variant is most likely pathogenic based on the prevailing computational evidence, though one high‑accuracy tool suggests a benign effect. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-5.819	Likely Benign	0.691	Likely Pathogenic	Likely Benign										0.308	Likely Benign	-4.96	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.1790	0.4061		0	-2	-1.6	40.02
c.2360C>T	P787L 2D AIThe SynGAP1 missense variant P787L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) lean toward pathogenicity, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750											-3.924	Likely Benign	0.747	Likely Pathogenic	Likely Benign										0.256	Likely Benign	-5.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.45	Pathogenic	0.01	Affected			0.2254	0.6034		-3	-3	5.4	16.04
c.2363C>A	S788Y 2D AIThe SynGAP1 missense variant S788Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, AlphaMissense‑Optimized is uncertain (treated as unavailable), and Foldetta results are not provided. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-8.745	Likely Pathogenic	0.795	Likely Pathogenic	Ambiguous										0.251	Likely Benign	-4.56	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0844	0.5551		-3	-2	-0.5	76.10
c.2363C>T	S788F 2D AIThe SynGAP1 missense variant S788F is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; Foldetta stability analysis is unavailable. Overall, the preponderance of predictions 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	SH3-binding motif	0.956248	Disordered	0.573557	Binding	0.349	0.895	0.750											-7.870	In-Between	0.749	Likely Pathogenic	Likely Benign										0.275	Likely Benign	-4.73	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0781	0.5824		-3	-2	3.6	60.10
c.2366C>G	P789R 2D AIThe SynGAP1 missense variant P789R 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, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-2.503	Likely Benign	0.668	Likely Pathogenic	Likely Benign										0.354	Likely Benign	-5.04	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1353	0.2129		0	-2	-2.9	59.07
c.2408A>C	K803T 2D AIThe SynGAP1 missense variant K803T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicate it is likely pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM‑Consensus indicates it is likely pathogenic; a Foldetta stability analysis is not available. Overall, the balance of evidence points to a pathogenic effect for K803T, 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	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-3.571	Likely Benign	0.584	Likely Pathogenic	Likely Benign										0.121	Likely Benign	-2.90	Deleterious	0.946	Possibly Damaging	0.741	Possibly Damaging	2.40	Pathogenic	0.00	Affected			0.2417	0.4395		0	-1	3.2	-27.07
c.2408A>T	K803I 2D AIThe SynGAP1 K803I 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized assessment is uncertain, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for K803I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.207	Likely Benign	0.894	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.06	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.1425	0.3889		-2	-3	8.4	-15.01
c.2410G>C	D804H 2D AIThe SynGAP1 D804H missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions suggests that D804H is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-5.100	Likely Benign	0.821	Likely Pathogenic	Ambiguous										0.296	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	1.19	Pathogenic	0.01	Affected			0.1859	0.7607		1	-1	0.3	22.05
c.2410G>T	D804Y 2D AIThe SynGAP1 missense variant D804Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, therefore classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of predictions support a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-8.356	Likely Pathogenic	0.782	Likely Pathogenic	Likely Benign										0.357	Likely Benign	-5.16	Deleterious	0.999	Probably Damaging	0.983	Probably Damaging	1.18	Pathogenic	0.01	Affected			0.0886	0.6653		-4	-3	2.2	48.09
c.2411A>C	D804A 2D AIThe SynGAP1 D804A missense variant is catalogued in gnomAD (ID 6‑33442963‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized indicates a benign change, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability 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 points to a pathogenic 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 Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625								6-33442963-A-C			-6.086	Likely Benign	0.758	Likely Pathogenic	Likely Benign										0.269	Likely Benign	-3.99	Deleterious	0.980	Probably Damaging	0.858	Possibly Damaging	1.21	Pathogenic	0.04	Affected	3.77	5	0.3716	0.6824		-2	0	5.3	-44.01
c.2411A>G	D804G 2D AIThe SynGAP1 missense variant D804G is catalogued in gnomAD (ID 6‑33442963‑A‑G) but has no ClinVar entry. Prediction tools cluster into two groups: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625								6-33442963-A-G	1	6.20e-7	-5.051	Likely Benign	0.680	Likely Pathogenic	Likely Benign										0.287	Likely Benign	-3.82	Deleterious	0.980	Probably Damaging	0.858	Possibly Damaging	1.21	Pathogenic	0.04	Affected	3.77	5	0.3854	0.6488		-1	1	3.1	-58.04
c.2411A>T	D804V 2D AIThe SynGAP1 missense variant D804V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic impact. The AlphaMissense‑Optimized score is uncertain, providing no definitive evidence. High‑accuracy assessments show that the SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome; AlphaMissense‑Optimized remains inconclusive, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for D804V, 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	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625											-8.143	Likely Pathogenic	0.832	Likely Pathogenic	Ambiguous										0.402	Likely Benign	-4.77	Deleterious	0.997	Probably Damaging	0.951	Probably Damaging	1.19	Pathogenic	0.01	Affected			0.1196	0.6981		-2	-3	7.7	-15.96
c.2414T>G	L805R 2D AIThe SynGAP1 missense variant L805R is 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 AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as likely pathogenic; Foldetta results are unavailable. Overall, the balance of evidence from the broader set of predictors leans toward pathogenicity, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-6.640	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.196	Likely Benign	-3.00	Deleterious	0.927	Possibly Damaging	0.617	Possibly Damaging	2.37	Pathogenic	0.00	Affected			0.1372	0.0908		-3	-2	-8.3	43.03
c.2416T>A	F806I 2D AIThe SynGAP1 missense variant F806I 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, ESM1b, and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the balance of evidence from the consensus of prediction algorithms points to a pathogenic impact for F806I. 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.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-5.040	Likely Benign	0.744	Likely Pathogenic	Likely Benign										0.182	Likely Benign	-3.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.15	Pathogenic	0.03	Affected			0.2583	0.1357		1	0	1.7	-34.02
c.2416T>C	F806L 2D AIThe SynGAP1 missense variant F806L is 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 ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a consensus pathogenic signal from SGM‑Consensus—suggests that F806L is most likely pathogenic. 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	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2416T>G	F806V 2D AIThe SynGAP1 missense variant F806V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; a Foldetta stability analysis is unavailable. Overall, the balance of evidence from the majority of prediction algorithms points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-4.548	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-3.79	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.16	Pathogenic	0.02	Affected			0.2464	0.1325		-1	-1	1.4	-48.04
c.2417T>C	F806S 2D AIThe SynGAP1 missense variant F806S is catalogued in gnomAD (ID 6‑33442969‑T‑C) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is reported. 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	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500								6-33442969-T-C	1	6.20e-7	-6.959	Likely Benign	0.911	Likely Pathogenic	Ambiguous										0.269	Likely Benign	-4.13	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.21	Pathogenic	0.00	Affected	3.77	5	0.5067	0.0391	Weaken	-2	-3	-3.6	-60.10
c.2417T>G	F806C 2D AIThe SynGAP1 missense variant F806C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while SGM‑Consensus remains likely pathogenic; Foldetta results are unavailable. Based on the predominance of pathogenic predictions and the SGM‑Consensus outcome, 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	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-8.565	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous										0.266	Likely Benign	-4.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.3071	0.1125		-4	-2	-0.3	-44.04
c.2418C>A	F806L 2D AIThe SynGAP1 missense variant F806L is 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 ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a consensus pathogenic signal from SGM‑Consensus—suggests that F806L is most likely pathogenic. 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	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2418C>G	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign predictions come from REVEL, SIFT, and ESM1b, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus method SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a likely pathogenic verdict (3/4 pathogenic votes). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta stability assessment is available. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion aligns with the SGM‑Consensus prediction; it does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2419T>A	Y807N 2D AIThe SynGAP1 missense variant Y807N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which is labeled Likely Pathogenic. ESM1b is uncertain. High‑accuracy methods give a clearer picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, a protein‑folding stability approach that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. 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	SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-7.795	In-Between	0.591	Likely Pathogenic	Likely Benign										0.154	Likely Benign	-4.01	Deleterious	0.934	Possibly Damaging	0.773	Possibly Damaging	2.43	Pathogenic	0.00	Affected			0.2274	0.0704		-2	-2	-2.2	-49.07
c.2419T>G	Y807D 2D AIThe SynGAP1 missense variant Y807D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, while the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Uncertain calls come from ESM1b and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for Y807D, 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	SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-7.598	In-Between	0.862	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-4.40	Deleterious	0.966	Probably Damaging	0.773	Possibly Damaging	2.42	Pathogenic	0.00	Affected			0.3944	0.0704		-4	-3	-2.2	-48.09
c.2423T>A	V808E 2D AIThe SynGAP1 missense variant V808E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic, and Foldetta data are not available. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-9.078	Likely Pathogenic	0.888	Likely Pathogenic	Ambiguous										0.307	Likely Benign	-2.84	Deleterious	0.999	Probably Damaging	0.958	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1129	0.2787		-2	-2	-7.7	29.98
c.2428C>A	R810S 2D AIThe SynGAP1 R810S missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions suggests that R810S is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-5.996	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.204	Likely Benign	-3.20	Deleterious	0.996	Probably Damaging	0.900	Possibly Damaging	2.44	Pathogenic	0.01	Affected			0.3152	0.4556		0	-1	3.7	-69.11
c.2428C>G	R810G 2D AISynGAP1 missense variant R810G is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: a single benign call from REVEL, and six pathogenic calls from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Two tools (ESM1b and AlphaMissense‑Optimized) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic impact for R810G, 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 Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-7.190	In-Between	0.828	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-3.57	Deleterious	0.996	Probably Damaging	0.925	Probably Damaging	2.35	Pathogenic	0.01	Affected			0.3686	0.4207		-3	-2	4.1	-99.14
c.2428C>T	R810C 2D AIThe SynGAP1 missense variant R810C is listed in gnomAD (6‑33442980‑C‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of evidence points to a 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	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375								6-33442980-C-T	2	1.24e-6	-8.925	Likely Pathogenic	0.839	Likely Pathogenic	Ambiguous										0.245	Likely Benign	-4.91	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	2.32	Pathogenic	0.00	Affected	3.77	5	0.3517	0.4263		-3	-4	7.0	-53.05
c.2429G>C	R810P 2D AIThe SynGAP1 missense variant R810P is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus (a majority vote of 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 multiple in silico predictors points to a pathogenic impact for R810P. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-4.120	Likely Benign	0.779	Likely Pathogenic	Likely Benign										0.316	Likely Benign	-4.08	Deleterious	1.000	Probably Damaging	0.977	Probably Damaging	2.33	Pathogenic	0.01	Affected			0.2307	0.5478		0	-2	2.9	-59.07
c.2429G>T	R810L 2D AIThe SynGAP1 R810L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, while the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. Uncertain calls come from ESM1b and AlphaMissense‑Optimized. 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 results are unavailable. Overall, the preponderance of evidence from multiple in‑silico predictors points to a pathogenic impact for R810L. 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	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-7.172	In-Between	0.834	Likely Pathogenic	Ambiguous										0.338	Likely Benign	-4.57	Deleterious	0.996	Probably Damaging	0.925	Probably Damaging	2.35	Pathogenic	0.01	Affected			0.2019	0.5271		-3	-2	8.3	-43.03
c.2443C>T	R815C 2D AIThe SynGAP1 missense variant R815C is listed in ClinVar (ID 660618.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442995‑C‑T). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is “Uncertain.” The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “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 predictions indicates a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification but suggests that the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Uncertain		1	6-33442995-C-T	5	3.10e-6	-9.373	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous										0.174	Likely Benign	-3.89	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected	4.32	4	0.3389	0.3682		-4	-3	7.0	-53.05
c.2444G>T	R815L 2D AISynGAP1 missense variant R815L is listed in ClinVar (ID 2505666.0) with an uncertain significance annotation 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, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools indicates a pathogenic effect, which contrasts with the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Uncertain		1				-8.546	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.63	Benign	0.03	Affected	4.32	4	0.1817	0.5132		-2	-3	8.3	-43.03
c.2447C>A	S816Y 2D AIThe SynGAP1 missense variant S816Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default, all of which classify the substitution as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an uncertain result, while Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus, the variant is most likely pathogenic; 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		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-8.369	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-2.83	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.60	Benign	0.03	Affected			0.0668	0.4741		-3	-2	-0.5	76.10
c.2447C>T	S816F 2D AIThe SynGAP1 missense variant S816F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. When predictions are grouped, two tools predict benign and six predict pathogenic. High‑accuracy assessment further supports a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both conventional and high‑accuracy predictors indicates that S816F is most likely pathogenic, 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		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-8.804	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.232	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.59	Benign	0.03	Affected			0.0605	0.5014		-3	-2	3.6	60.10
c.2449T>C	S817P 2D AIThe SynGAP1 missense variant S817P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools and the consensus score indicate 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		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-4.633	Likely Benign	0.724	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-3.26	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.39	Pathogenic	0.00	Affected			0.2272	0.6023		1	-1	-0.8	10.04
c.2450C>T	S817L 2D AIThe SynGAP1 missense variant S817L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic 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		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-7.612	In-Between	0.659	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-3.90	Deleterious	0.997	Probably Damaging	0.945	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1226	0.5662		-3	-2	4.6	26.08
c.2452C>A	P818T 2D AIThe SynGAP1 missense variant P818T 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.864	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.265	Likely Benign	-4.58	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.01	Pathogenic	0.02	Affected			0.1797	0.6453		0	-1	0.9	3.99
c.2452C>G	P818A 2D AIThe SynGAP1 missense variant P818A is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 HumVar, SIFT, and ESM1b, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default. When the predictions are grouped by consensus, four tools favor benign and four favor pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Taken together, the preponderance of evidence from both consensus and high‑accuracy tools indicates that 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		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.084	Likely Benign	0.820	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-4.37	Deleterious	0.543	Possibly Damaging	0.306	Benign	2.15	Pathogenic	0.06	Tolerated			0.3574	0.5724		1	-1	3.4	-26.04
c.2452C>T	P818S 2D AIThe SynGAP1 missense variant P818S is catalogued in gnomAD (ID 6‑33443004‑C‑T) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments are limited: AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. Taken together, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625								6-33443004-C-T	1	6.20e-7	-5.740	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-4.38	Deleterious	0.989	Probably Damaging	0.824	Possibly Damaging	2.04	Pathogenic	0.04	Affected	3.77	5	0.3581	0.6199		-1	1	0.8	-10.04
c.2453C>A	P818Q 2D AIThe SynGAP1 missense variant P818Q is not listed in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled 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 P818Q 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		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.855	Likely Benign	0.969	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-4.07	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	1.97	Pathogenic	0.27	Tolerated			0.1569	0.5456		0	-1	-1.9	31.01
c.2453C>G	P818R 2D AIThe SynGAP1 missense variant P818R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. ESM1b is uncertain and does not contribute to a consensus. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Pathogenic” designation. AlphaMissense‑Optimized independently predicts pathogenicity, while Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-7.267	In-Between	0.976	Likely Pathogenic	Likely Pathogenic										0.374	Likely Benign	-5.12	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	1.97	Pathogenic	0.03	Affected			0.1499	0.4547		0	-2	-2.9	59.07
c.2453C>T	P818L 2D AIThe SynGAP1 missense variant P818L is catalogued in gnomAD (ID 6‑33443005‑C‑T) but has no ClinVar entry. Functional prediction tools fall into two consensus groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments are limited: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates “Likely Pathogenic,” and Foldetta data are unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Thus, the variant is most likely pathogenic based on current predictive tools. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625								6-33443005-C-T	1	6.20e-7	-6.064	Likely Benign	0.938	Likely Pathogenic	Ambiguous										0.285	Likely Benign	-5.81	Deleterious	0.997	Probably Damaging	0.954	Probably Damaging	1.98	Pathogenic	0.02	Affected	3.77	5	0.2351	0.6951		-3	-3	5.4	16.04
c.2455G>C	A819P 2D AIThe SynGAP1 missense variant A819P is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A819P, 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		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-5.542	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.342	Likely Benign	-3.18	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	2.17	Pathogenic	0.01	Affected			0.1920	0.5753		1	-1	-3.4	26.04
c.2456C>A	A819E 2D AIThe SynGAP1 missense variant A819E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. ESM1b is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, 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		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-7.333	In-Between	0.982	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-2.85	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.19	Pathogenic	0.00	Affected			0.1189	0.2037		0	-1	-5.3	58.04
c.2458T>G	Y820D 2D AIThe SynGAP1 missense variant Y820D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that Y820D is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-10.497	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-2.77	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.73	Benign	0.08	Tolerated			0.4113	0.0704		-4	-3	-2.2	-48.09
c.2459A>G	Y820C 2D AIThe SynGAP1 missense variant Y820C 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, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence—including the SGM‑Consensus—suggests 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		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625					Uncertain		1				-8.797	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign										0.113	Likely Benign	-3.16	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.68	Benign	0.06	Tolerated	3.77	5	0.3177	0.1915		0	-2	3.8	-60.04
c.2467A>C	S823R 2D AIThe SynGAP1 missense variant S823R 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools points to a pathogenic effect for S823R, 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		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.293	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2467A>G	S823G 2D AIThe SynGAP1 missense variant S823G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the Foldetta stability analysis is 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		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.034	Likely Benign	0.822	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.2855	0.5287		1	0	0.4	-30.03
c.2467A>T	S823C 2D AIThe SynGAP1 missense variant S823C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability prediction is available, so it does not contribute to the assessment. Overall, the preponderance of evidence points to a pathogenic effect for S823C, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-7.881	In-Between	0.911	Likely Pathogenic	Ambiguous										0.332	Likely Benign	-3.80	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.1019	0.6137		0	-1	3.3	16.06
c.2468G>T	S823I 2D AIThe SynGAP1 missense variant S823I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only REVEL predicts a benign outcome, while ESM1b remains uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-7.332	In-Between	0.990	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-4.26	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.0964	0.5848		-1	-2	5.3	26.08
c.2469C>A	S823R 2D AIThe SynGAP1 missense variant S823R 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, 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, 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		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2469C>G	S823R 2D AIThe SynGAP1 missense variant S823R 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, 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, 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		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2473T>C	S825P 2D AIThe SynGAP1 missense variant S825P 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S825P is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-3.227	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.285	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.94	Pathogenic	0.02	Affected			0.2060	0.5998		1	-1	-0.8	10.04
c.2474C>G	S825W 2D AIThe SynGAP1 missense variant S825W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign, representing the sole benign prediction. High‑accuracy methods further support a pathogenic interpretation: AlphaMissense‑Optimized returns a pathogenic score, and the SGM‑Consensus indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, indicates that S825W is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-8.396	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.316	Likely Benign	-5.25	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0818	0.6083		-2	-3	-0.1	99.14
c.2474C>T	S825L 2D AIThe SynGAP1 missense variant S825L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443026‑C‑T). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. 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 “Uncertain,” and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, 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		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750					Uncertain		1	6-33443026-C-T	1	6.20e-7	-4.987	Likely Benign	0.910	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-4.30	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.94	Pathogenic	0.01	Affected	3.77	5	0.1252	0.5747		-2	-3	4.6	26.08
c.2476G>C	D826H 2D AIThe SynGAP1 missense variant D826H 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 D826H 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		0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-6.437	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.345	Likely Benign	-3.00	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1757	0.8651		1	-1	0.3	22.05
c.2476G>T	D826Y 2D AIThe SynGAP1 missense variant D826Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—label it pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus also indicates Likely Pathogenic; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a pathogenic effect for D826Y. Thus, the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-8.029	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.336	Likely Benign	-4.25	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.47	Pathogenic	0.00	Affected			0.0683	0.7410		-4	-3	2.2	48.09
c.2477A>T	D826V 2D AIThe SynGAP1 missense variant D826V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for D826V, and this conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-6.918	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.428	Likely Benign	-4.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.1017	0.8023		-2	-3	7.7	-15.96
c.2485G>A	E829K 2D AIThe SynGAP1 missense variant E829K is listed in ClinVar as Pathogenic (ClinVar ID 1721258.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only REVEL predicts a benign outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E829K is most likely pathogenic, and this conclusion aligns with the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375					Pathogenic		1				-7.527	In-Between	0.807	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-2.65	Deleterious	0.994	Probably Damaging	0.900	Possibly Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.2400	0.7372		0	1	-0.4	-0.94
c.2486A>C	E829A 2D AIThe SynGAP1 missense variant E829A 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Overall, the majority of evidence—including the SGM‑Consensus—points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.096	Likely Benign	0.574	Likely Pathogenic	Likely Benign										0.265	Likely Benign	-3.75	Deleterious	0.994	Probably Damaging	0.926	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.4707	0.7255		0	-1	5.3	-58.04
c.2486A>G	E829G 2D AIThe SynGAP1 missense variant E829G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, with one high‑accuracy tool suggesting benign. No ClinVar annotation 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		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.152	Likely Benign	0.593	Likely Pathogenic	Likely Benign										0.316	Likely Benign	-4.52	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.3517	0.6557		0	-2	3.1	-72.06
c.2486A>T	E829V 2D AIThe SynGAP1 missense variant E829V 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority of the four high‑accuracy inputs) remains pathogenic; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-5.142	Likely Benign	0.719	Likely Pathogenic	Likely Benign										0.296	Likely Benign	-4.86	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.21	Pathogenic	0.00	Affected			0.0835	0.7984		-2	-2	7.7	-29.98
c.2492A>T	E831V 2D AIThe SynGAP1 missense variant E831V is not reported in ClinVar and has no gnomAD allele. Prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts a benign effect, SGM‑Consensus indicates a likely pathogenic outcome, and Foldetta data are unavailable. Overall, the majority of evidence points to a pathogenic effect, 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		0.626927	Disordered	0.617732	Binding	0.319	0.874	0.375											-6.327	Likely Benign	0.629	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-3.43	Deleterious	0.891	Possibly Damaging	0.492	Possibly Damaging	2.32	Pathogenic	0.02	Affected			0.0604	0.7407		-2	-2	7.7	-29.98
c.250C>T	R84C 2D AIThe SynGAP1 missense variant R84C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R84C is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-9.044	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.243	Likely Benign	-3.25	Deleterious	0.999	Probably Damaging	0.876	Possibly Damaging	3.66	Benign	0.00	Affected			0.3281	0.3657		-4	-3	7.0	-53.05
c.2512A>T	N838Y 2D AIThe SynGAP1 missense variant N838Y 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, 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, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (six pathogenic versus three benign) and the SGM‑Consensus 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.	Likely Pathogenic		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-9.020	Likely Pathogenic	0.722	Likely Pathogenic	Likely Benign										0.266	Likely Benign	-4.09	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.62	Benign	0.05	Affected			0.0621	0.4258		-2	-2	2.2	49.07
c.2513A>T	N838I 2D AIThe SynGAP1 missense variant N838I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of algorithms predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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 show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for N838I. This conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-8.061	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-4.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.63	Benign	0.01	Affected			0.0642	0.4900		-2	-3	8.0	-0.94
c.2514C>A	N838K 2D AIThe SynGAP1 missense variant N838K is listed in ClinVar with an “Uncertain” status (ClinVar ID 1377909.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, 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 “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the balance of evidence leans toward a pathogenic interpretation, 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		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250					Uncertain		2				-8.470	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.097	Likely Benign	-2.78	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.69	Benign	0.16	Tolerated	3.77	5	0.2187	0.3866		1	0	-0.4	14.07
c.2514C>G	N838K 2D AIThe SynGAP1 missense variant N838K 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 arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized yields an Uncertain result and Foldetta data are unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250											-8.470	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.097	Likely Benign	-2.78	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.69	Benign	0.16	Tolerated	3.77	5	0.2187	0.3866		1	0	-0.4	14.07
c.2515A>C	K839Q 2D AIThe SynGAP1 missense variant K839Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions and the consensus call indicate a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.631	Likely Pathogenic	0.694	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-1.98	Neutral	0.972	Probably Damaging	0.862	Possibly Damaging	2.47	Pathogenic	0.02	Affected			0.4544	0.1437		1	1	0.4	-0.04
c.2515A>G	K839E 2D AIThe SynGAP1 missense variant K839E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic predictions versus four benign, plus a Likely Pathogenic consensus—suggests the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-12.616	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.90	Neutral	0.316	Benign	0.139	Benign	2.47	Pathogenic	0.01	Affected			0.3822	0.1198		0	1	0.4	0.94
c.2516A>C	K839T 2D AIThe SynGAP1 missense variant K839T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign calls are limited to REVEL, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the consensus of the majority of in silico tools indicates that K839T is most likely pathogenic, and this conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-11.946	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.235	Likely Benign	-3.79	Deleterious	0.986	Probably Damaging	0.922	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.2119	0.4164		0	-1	3.2	-27.07
c.2516A>T	K839M 2D AIThe SynGAP1 missense variant K839M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL indicates a benign likelihood, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM consensus also reports a likely pathogenic outcome. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-13.688	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.241	Likely Benign	-3.54	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.40	Pathogenic	0.00	Affected			0.1253	0.4481		0	-1	5.8	3.02
c.2517G>C	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2517G>T	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2518A>C	S840R 2D AIThe SynGAP1 missense variant S840R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that S840R is most likely pathogenic, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.366	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-3.27	Deleterious	0.993	Probably Damaging	0.904	Possibly Damaging	1.51	Pathogenic	0.00	Affected			0.0726	0.3328		0	-1	-3.7	69.11
c.2518A>G	S840G 2D AIThe SynGAP1 missense variant S840G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S840G, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-8.117	Likely Pathogenic	0.674	Likely Pathogenic	Likely Benign										0.163	Likely Benign	-2.72	Deleterious	0.889	Possibly Damaging	0.663	Possibly Damaging	1.54	Pathogenic	0.00	Affected			0.2354	0.3858		1	0	0.4	-30.03
c.2518A>T	S840C 2D AIThe SynGAP1 missense variant S840C is listed in ClinVar (ID 2089808.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Pathogenic,” and Foldetta results are unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for S840C. This conclusion aligns with the ClinVar designation of uncertainty rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250					Uncertain		1				-8.799	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous										0.376	Likely Benign	-3.96	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	1.50	Pathogenic	0.00	Affected	3.77	5	0.0803	0.5481		0	-1	3.3	16.06
c.2519G>A	S840N 2D AIThe SynGAP1 missense variant S840N is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and both polyPhen‑2 HumDiv and HumVar scores. Tools that predict a pathogenic effect are SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, while AlphaMissense‑Optimized is uncertain. 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 (including the SGM consensus) indicate a pathogenic impact, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.849	Likely Pathogenic	0.891	Likely Pathogenic	Ambiguous										0.130	Likely Benign	-1.65	Neutral	0.206	Benign	0.098	Benign	1.52	Pathogenic	0.00	Affected			0.0934	0.4181		1	1	-2.7	27.03
c.2519G>T	S840I 2D AIThe SynGAP1 missense variant S840I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus indicates likely pathogenic. Foldetta results are not available, so they do not influence the overall assessment. Based on the consensus of the majority of prediction tools and the high‑accuracy methods, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-12.509	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.357	Likely Benign	-4.31	Deleterious	0.998	Probably Damaging	0.967	Probably Damaging	1.51	Pathogenic	0.00	Affected			0.0788	0.5251		-1	-2	5.3	26.08
c.2520T>A	S840R 2D AIThe SynGAP1 missense variant S840R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign, representing the sole benign prediction. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized returns a pathogenic score, and the SGM‑Consensus indicates “Likely Pathogenic.” 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 in silico tools and high‑accuracy predictors indicates that S840R 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		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.366	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.244	Likely Benign	-3.27	Deleterious	0.993	Probably Damaging	0.904	Possibly Damaging	1.51	Pathogenic	0.00	Affected			0.0726	0.3328		0	-1	-3.7	69.11
c.2520T>G	S840R 2D AIThe SynGAP1 missense variant S840R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign, representing the sole benign prediction. High‑accuracy assessments further support a pathogenic outcome: AlphaMissense‑Optimized returns a pathogenic score, and the SGM‑Consensus indicates “Likely Pathogenic.” 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 in silico tools and high‑accuracy predictors indicates that S840R is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.366	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.244	Likely Benign	-3.27	Deleterious	0.993	Probably Damaging	0.904	Possibly Damaging	1.51	Pathogenic	0.00	Affected			0.0726	0.3328		0	-1	-3.7	69.11
c.2522T>A	V841E 2D AIThe SynGAP1 missense variant V841E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction tools and high‑accuracy methods indicates that V841E 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		0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-13.750	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-3.13	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.52	Benign	0.00	Affected			0.0939	0.1656		-2	-2	-7.7	29.98
c.2524T>A	S842T 2D AIThe SynGAP1 missense variant S842T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus (majority of the four high‑accuracy predictors) is Pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for S842T, 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		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-13.443	Likely Pathogenic	0.725	Likely Pathogenic	Likely Benign										0.163	Likely Benign	-2.23	Neutral	0.983	Probably Damaging	0.702	Possibly Damaging	2.15	Pathogenic	0.00	Affected			0.0974	0.5391		1	1	0.1	14.03
c.2524T>C	S842P 2D AIThe SynGAP1 missense variant S842P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, indicates that S842P is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-13.890	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-3.43	Deleterious	0.995	Probably Damaging	0.892	Possibly Damaging	1.99	Pathogenic	0.00	Affected			0.1494	0.5342		1	-1	-0.8	10.04
c.2524T>G	S842A 2D AIThe SynGAP1 missense variant S842A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) indicate a pathogenic 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 Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-13.601	Likely Pathogenic	0.656	Likely Pathogenic	Likely Benign										0.180	Likely Benign	-2.37	Neutral	0.889	Possibly Damaging	0.614	Possibly Damaging	2.09	Pathogenic	0.00	Affected			0.3971	0.4223		1	1	2.6	-16.00
c.2525C>A	S842Y 2D AIThe SynGAP1 missense variant S842Y is listed in ClinVar as Pathogenic (ClinVar ID 624244.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled 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 indicates that the variant is most likely pathogenic, in agreement with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250					Likely Pathogenic		1				-16.124	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-4.28	Deleterious	0.944	Possibly Damaging	0.676	Possibly Damaging	1.97	Pathogenic	0.00	Affected	3.77	5	0.0576	0.5403		-3	-2	-0.5	76.10
c.2525C>G	S842C 2D AIThe SynGAP1 missense variant S842C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, while the Foldetta stability analysis is unavailable. Based on the collective evidence, the variant is most likely pathogenic; this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-12.405	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous										0.233	Likely Benign	-3.93	Deleterious	0.999	Probably Damaging	0.944	Probably Damaging	1.98	Pathogenic	0.00	Affected			0.0806	0.5506		0	-1	3.3	16.06
c.2525C>T	S842F 2D AIThe SynGAP1 missense variant S842F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL, polyPhen‑2 HumDiv and HumVar, whereas pathogenic calls come from PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default and AlphaMissense‑Optimized. The consensus predictor 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, and the SGM‑Consensus result is consistent with this. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-14.590	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-4.12	Deleterious	0.029	Benign	0.043	Benign	1.98	Pathogenic	0.00	Affected			0.0584	0.5692		-3	-2	3.6	60.10
c.2528T>A	M843K 2D AIThe SynGAP1 missense variant M843K 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 remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. 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 M843K is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-13.256	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.442	Likely Benign	-3.60	Deleterious	0.968	Probably Damaging	0.969	Probably Damaging	2.60	Benign	0.00	Affected			0.1763	0.0940		0	-1	-5.8	-3.02
c.2528T>G	M843R 2D AIThe SynGAP1 missense variant M843R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that M843R is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-12.044	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.430	Likely Benign	-3.78	Deleterious	0.968	Probably Damaging	0.978	Probably Damaging	2.59	Benign	0.00	Affected			0.1819	0.0922		0	-1	-6.4	24.99
c.2531T>G	L844R 2D AIThe SynGAP1 missense variant L844R 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, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375											-9.355	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous										0.267	Likely Benign	-2.77	Deleterious	0.960	Probably Damaging	0.697	Possibly Damaging	2.60	Benign	0.01	Affected			0.1230	0.0947		-3	-2	-8.3	43.03
c.2533G>A	D845N 2D AIThe SynGAP1 missense variant D845N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized remains 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 that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.586	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-3.42	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.1216	0.7112		2	1	0.0	-0.98
c.2533G>C	D845H 2D AIThe SynGAP1 missense variant D845H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL indicates a benign likelihood, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM consensus also reports a likely pathogenic status. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is consistent with the absence of a ClinVar entry (no contradictory status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-8.613	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-5.08	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.1394	0.7515		1	-1	0.3	22.05
c.2533G>T	D845Y 2D AIThe SynGAP1 missense variant D845Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that D845Y is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-9.917	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.384	Likely Benign	-6.55	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0590	0.6699		-4	-3	2.2	48.09
c.2534A>C	D845A 2D AIThe SynGAP1 missense variant D845A 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 ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts 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 from both general and high‑accuracy predictors indicates that D845A is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.482	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.376	Likely Benign	-5.67	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.3999	0.6731		0	-2	5.3	-44.01
c.2534A>G	D845G 2D AIThe SynGAP1 missense variant D845G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a Likely Pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence indicates that D845G is most likely pathogenic, and this assessment does not conflict with the current ClinVar record, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-8.209	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.399	Likely Benign	-4.96	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.3953	0.6740		1	-1	3.1	-58.04
c.2534A>T	D845V 2D AIThe SynGAP1 D845V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a harmful outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic; Foldetta results are not available. Taken together, the overwhelming majority of evidence points to a pathogenic effect. 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		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-8.914	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-6.15	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.00	Affected			0.0871	0.7088		-2	-3	7.7	-15.96
c.2535C>A	D845E 2D AIThe SynGAP1 missense variant D845E is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta stability analysis is unavailable. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. Overall, the balance of evidence points to a pathogenic effect for D845E, 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		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.979	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-2.67	Deleterious	0.992	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1404	0.6998		3	2	0.0	14.03
c.2535C>G	D845E 2D AIThe SynGAP1 missense variant D845E 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect for D845E, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.979	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-2.67	Deleterious	0.992	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1404	0.6998		3	2	0.0	14.03
c.2536T>G	L846V 2D AIThe SynGAP1 missense variant L846V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not conflict with any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-8.326	Likely Pathogenic	0.569	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.07	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.20	Pathogenic	0.00	Affected			0.1540	0.3126		2	1	0.4	-14.03
c.2537T>C	L846S 2D AIThe SynGAP1 missense variant L846S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.944	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-3.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.3128	0.1070		-3	-2	-4.6	-26.08
c.2538A>C	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Overall, the preponderance of evidence from multiple high‑accuracy predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2538A>T	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic or deleterious impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2539C>A	Q847K 2D AIThe SynGAP1 missense variant Q847K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Pathogenic verdict. High‑accuracy assessments further indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus remains Likely Pathogenic; no Foldetta stability data are available. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the SGM Consensus result. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-5.507	Likely Benign	0.736	Likely Pathogenic	Likely Benign										0.214	Likely Benign	-2.82	Deleterious	0.481	Possibly Damaging	0.373	Benign	2.32	Pathogenic	0.00	Affected			0.1694	0.4129		1	1	-0.4	0.04
c.2540A>G	Q847R 2D AIThe SynGAP1 missense variant Q847R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Optimized; pathogenic calls come from PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Thus, the overall prediction leans toward benign based on the majority of tools, but the high‑accuracy SGM‑Consensus contradicts this by indicating likely pathogenic. No ClinVar annotation exists, so there is no conflict with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-3.232	Likely Benign	0.662	Likely Pathogenic	Likely Benign										0.256	Likely Benign	-2.63	Deleterious	0.014	Benign	0.026	Benign	2.30	Pathogenic	0.00	Affected			0.1404	0.1979		1	1	-1.0	28.06
c.2540A>T	Q847L 2D AIThe SynGAP1 missense variant Q847L 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, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-6.966	Likely Benign	0.625	Likely Pathogenic	Likely Benign										0.326	Likely Benign	-4.52	Deleterious	0.818	Possibly Damaging	0.637	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.0701	0.5132		-2	-2	7.3	-14.97
c.2541G>C	Q847H 2D AIThe SynGAP1 missense variant Q847H 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, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) and the SGM‑Consensus result point to a pathogenic effect. 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		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-4.208	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-2.82	Deleterious	0.990	Probably Damaging	0.925	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.1429	0.3634		3	0	0.3	9.01
c.2541G>T	Q847H 2D AIThe SynGAP1 missense variant Q847H 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, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) and the SGM‑Consensus support 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.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-4.208	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-2.82	Deleterious	0.990	Probably Damaging	0.925	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.1429	0.3634		3	0	0.3	9.01
c.254C>T	T85I 2D AIThe SynGAP1 missense variant T85I 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 a majority of tools (PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized also predicts pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from multiple independent predictors indicates that T85I 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		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-9.310	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.113	Likely Benign	-2.50	Deleterious	0.813	Possibly Damaging	0.072	Benign	3.82	Benign	0.00	Affected			0.0634	0.5443		0	-1	5.2	12.05
c.2582C>G	S861W 2D AIThe SynGAP1 missense variant S861W 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, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority of the four high‑accuracy tools) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250											-8.538	Likely Pathogenic	0.585	Likely Pathogenic	Likely Benign										0.267	Likely Benign	-3.13	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	3.89	Benign	0.01	Affected			0.0874	0.6247		-2	-3	-0.1	99.14
c.2599G>T	G867W 2D AIThe SynGAP1 missense variant G867W 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, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come 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, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250											-8.983	Likely Pathogenic	0.776	Likely Pathogenic	Likely Benign										0.163	Likely Benign	-2.95	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.64	Benign	0.01	Affected			0.0726	0.4584		-7	-2	-0.5	129.16
c.2602G>T	D868Y 2D AIThe SynGAP1 missense variant D868Y 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 ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate deleteriousness. 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 Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for D868Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-6.031	Likely Benign	0.815	Likely Pathogenic	Ambiguous										0.256	Likely Benign	-2.90	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.47	Pathogenic	0.05	Affected			0.1115	0.6847		-4	-3	2.2	48.09
c.2603A>T	D868V 2D AIThe SynGAP1 missense variant D868V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-5.200	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.182	Likely Benign	-3.17	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.49	Pathogenic	0.25	Tolerated			0.1485	0.6753		-2	-3	7.7	-15.96
c.2618G>T	S873I 2D AIThe SynGAP1 missense variant S873I has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. High‑accuracy assessment therefore points to a Likely Pathogenic status from SGM‑Consensus, with AlphaMissense‑Optimized inconclusive and Foldetta missing. Overall, the preponderance of evidence suggests 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		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-9.412	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.305	Likely Benign	-3.44	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.02	Affected			0.1012	0.5560		-1	-2	5.3	26.08
c.2627C>G	S876W 2D AIThe SynGAP1 missense variant S876W is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID: 6‑33443179‑C‑G). 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, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM‑Consensus indicates a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus, the variant is most likely pathogenic; this assessment does not contradict ClinVar status, as no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250								6-33443179-C-G	1	6.20e-7	-9.305	Likely Pathogenic	0.829	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.54	Benign	0.01	Affected	3.77	5	0.0964	0.6700		-3	-2	-0.1	99.14
c.2644G>T	G882W 2D AIThe SynGAP1 missense variant G882W has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.690604	Disordered	0.632888	Binding	0.306	0.878	0.250											-8.637	Likely Pathogenic	0.606	Likely Pathogenic	Likely Benign										0.166	Likely Benign	-2.35	Neutral	0.983	Probably Damaging	0.813	Possibly Damaging	2.01	Pathogenic	0.00	Affected			0.0829	0.4616		-7	-2	-0.5	129.16
c.2693C>A	S898Y 2D AISynGAP1 missense variant S898Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools and the consensus prediction indicate 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		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500											-5.927	Likely Benign	0.712	Likely Pathogenic	Likely Benign										0.182	Likely Benign	-2.69	Deleterious	0.998	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1244	0.6838		-3	-2	-0.5	76.10
c.2693C>T	S898F 2D AIThe SynGAP1 missense variant S898F 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500											-5.242	Likely Benign	0.673	Likely Pathogenic	Likely Benign										0.181	Likely Benign	-2.87	Deleterious	0.998	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1183	0.6643		-3	-2	3.6	60.10
c.2770C>A	P924T 2D AIThe SynGAP1 missense variant P924T 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 P924T 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		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.360	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.400	Likely Benign	-6.03	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1190	0.4009		0	-1	0.9	3.99
c.2770C>G	P924A 2D AIThe SynGAP1 missense variant P924A 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an Uncertain result, SGM‑Consensus indicates Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-5.995	Likely Benign	0.854	Likely Pathogenic	Ambiguous										0.383	Likely Benign	-5.90	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.2904	0.3423		1	-1	3.4	-26.04
c.2770C>T	P924S 2D AIThe SynGAP1 missense variant P924S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect for P924S, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-4.686	Likely Benign	0.920	Likely Pathogenic	Ambiguous										0.388	Likely Benign	-5.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.2952	0.3772		1	-1	0.8	-10.04
c.2771C>A	P924H 2D AIThe SynGAP1 missense variant P924H 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 computational evidence indicates that P924H is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.236	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.457	Likely Benign	-5.87	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1317	0.3281		0	-2	-1.6	40.02
c.2771C>G	P924R 2D AIThe SynGAP1 missense variant P924R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL and ESM1b, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. Grouping by consensus, the pathogenic group outweighs the benign group. High‑accuracy assessments further support a deleterious effect: 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. Foldetta data are unavailable. Overall, the preponderance of evidence indicates that P924R 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		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.024	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.420	Likely Benign	-6.20	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1314	0.2083		0	-2	-2.9	59.07
c.2771C>T	P924L 2D AIThe SynGAP1 missense variant P924L 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 P924L 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		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.361	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.422	Likely Benign	-6.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1771	0.4941		-3	-3	5.4	16.04
c.2773C>T	L925F 2D AIThe SynGAP1 missense variant L925F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic impact for the L925F substitution, 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		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-4.147	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-3.04	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0897	0.2881		2	0	-1.0	34.02
c.2774T>A	L925H 2D AIThe SynGAP1 missense variant L925H 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability result is available. Overall, the majority of evidence points to a pathogenic effect for L925H, 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		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-3.369	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.475	Likely Benign	-5.24	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1219	0.1494		-2	-3	-7.0	23.98
c.2774T>C	L925P 2D AIThe SynGAP1 missense variant L925P 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 ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-2.733	Likely Benign	0.985	Likely Pathogenic	Likely Pathogenic										0.501	Likely Pathogenic	-5.12	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.3083	0.1996		-3	-3	-5.4	-16.04
c.2774T>G	L925R 2D AIThe SynGAP1 missense variant L925R 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 ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM‑Consensus indicates a likely pathogenic classification. Foldetta results are not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-2.340	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic										0.519	Likely Pathogenic	-4.54	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1278	0.1294		-3	-2	-8.3	43.03
c.2776T>C	S926P 2D AIThe SynGAP1 missense variant S926P 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 ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (pathogenic), and PROVEAN (pathogenic), yielding a Likely Pathogenic classification. AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S926P. 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		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-3.873	Likely Benign	0.916	Likely Pathogenic	Ambiguous										0.424	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.51	Pathogenic	0.00	Affected			0.1738	0.5058		1	-1	-0.8	10.04
c.2777C>A	S926Y 2D AIThe SynGAP1 missense variant S926Y 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for S926Y, 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	0.981753	Binding	0.295	0.854	0.250											-6.602	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.444	Likely Benign	-4.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0602	0.4932		-3	-2	-0.5	76.10
c.2777C>G	S926C 2D AIThe SynGAP1 missense variant S926C 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, ESM1b, and AlphaMissense‑Optimized, whereas tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of predictions lean toward pathogenicity, with the high‑accuracy AlphaMissense‑Optimized result providing a conflicting benign signal. Thus, the variant is most likely pathogenic based on the collective evidence, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-6.546	Likely Benign	0.680	Likely Pathogenic	Likely Benign										0.414	Likely Benign	-3.81	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0815	0.5487		0	-1	3.3	16.06
c.2777C>T	S926F 2D AIThe SynGAP1 missense variant S926F 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S926F is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-6.157	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic										0.458	Likely Benign	-4.57	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0585	0.5220		-3	-2	3.6	60.10
c.2779T>A	F927I 2D AIThe SynGAP1 missense variant F927I 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools indicates that F927I 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		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-4.793	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.370	Likely Benign	-4.50	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.34	Pathogenic	0.00	Affected			0.2255	0.1238		1	0	1.7	-34.02
c.2779T>C	F927L 2D AIThe SynGAP1 missense variant F927L 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that F927L is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-4.227	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-4.48	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.39	Pathogenic	0.00	Affected			0.2214	0.2209		2	0	1.0	-34.02
c.2779T>G	F927V 2D AIThe SynGAP1 missense variant F927V 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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 pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable and therefore not considered. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools indicates that the variant is most likely pathogenic, with no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-4.919	Likely Benign	0.996	Likely Pathogenic	Likely Pathogenic										0.470	Likely Benign	-5.21	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.34	Pathogenic	0.00	Affected			0.2207	0.1206		-1	-1	1.4	-48.04
c.2780T>C	F927S 2D AIThe SynGAP1 missense variant F927S 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized alone predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Based on the preponderance of pathogenic predictions—including the high‑accuracy consensus—the variant is most likely pathogenic, and this assessment 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		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-5.480	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.481	Likely Benign	-5.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.4748	0.0591		-3	-2	-3.6	-60.10
c.2780T>G	F927C 2D AIThe SynGAP1 missense variant F927C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are not available. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-8.298	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.523	Likely Pathogenic	-6.02	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.31	Pathogenic	0.00	Affected			0.2921	0.1291		-4	-2	-0.3	-44.04
c.2781C>A	F927L 2D AIThe SynGAP1 missense variant F927L 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that F927L is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-4.227	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.296	Likely Benign	-4.48	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.39	Pathogenic	0.00	Affected			0.2214	0.2209		2	0	1.0	-34.02
c.2781C>G	F927L 2D AIThe SynGAP1 missense variant F927L 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available. Based on the preponderance of pathogenic predictions and the high‑accuracy tools, 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		0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-4.227	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.296	Likely Benign	-4.48	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.39	Pathogenic	0.00	Affected			0.2214	0.2209		2	0	1.0	-34.02
c.2782C>A	Q928K 2D AIThe SynGAP1 missense variant Q928K has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. High‑accuracy evidence therefore consists of an uncertain AlphaMissense‑Optimized score, a Likely Pathogenic SGM‑Consensus, and an unavailable Foldetta prediction. Overall, the majority of tools predict pathogenicity, and there is no ClinVar status 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.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-4.941	Likely Benign	0.897	Likely Pathogenic	Ambiguous										0.259	Likely Benign	-2.80	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	1.60	Pathogenic	0.00	Affected			0.1728	0.5306		1	1	-0.4	0.04
c.2783A>C	Q928P 2D AIThe SynGAP1 missense variant Q928P 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus designation, the variant is most likely pathogenic; this assessment 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		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-6.275	Likely Benign	0.832	Likely Pathogenic	Ambiguous										0.441	Likely Benign	-4.28	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.2016	0.5768		0	-1	1.9	-31.01
c.2783A>G	Q928R 2D AIThe SynGAP1 missense variant Q928R is listed in gnomAD (ID 6‑33443335‑A‑G) but has no ClinVar entry. Functional prediction tools fall into two consensus groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta stability) data are available. High‑accuracy assessments therefore indicate a likely pathogenic outcome (SGM‑Consensus) with no contradictory evidence from ClinVar. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, 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.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250								6-33443335-A-G	1	6.20e-7	-4.089	Likely Benign	0.826	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-2.91	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.58	Pathogenic	0.00	Affected	4.32	4	0.1357	0.3453		1	1	-1.0	28.06
c.2783A>T	Q928L 2D AIThe SynGAP1 missense variant Q928L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion 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		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-6.237	Likely Benign	0.919	Likely Pathogenic	Ambiguous										0.373	Likely Benign	-4.57	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.0757	0.6091		-2	-2	7.3	-14.97
c.2784G>C	Q928H 2D AIThe SynGAP1 missense variant Q928H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion 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		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-4.358	Likely Benign	0.929	Likely Pathogenic	Ambiguous										0.329	Likely Benign	-3.65	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1389	0.4811		3	0	0.3	9.01
c.2784G>T	Q928H 2D AIThe SynGAP1 missense variant Q928H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion 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		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-4.358	Likely Benign	0.929	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-3.65	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1389	0.4811		3	0	0.3	9.01
c.2785A>C	N929H 2D AIThe SynGAP1 missense variant N929H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain, and Foldetta results are unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. With no conflicting ClinVar annotation, the collective evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-7.070	In-Between	0.967	Likely Pathogenic	Likely Pathogenic										0.342	Likely Benign	-3.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.1507	0.7659		2	1	0.3	23.04
c.2785A>G	N929D 2D AIThe SynGAP1 missense variant N929D 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which reports “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-6.856	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.365	Likely Benign	-3.86	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.49	Pathogenic	0.00	Affected			0.1991	0.4605		2	1	0.0	0.98
c.2785A>T	N929Y 2D AIThe SynGAP1 missense variant N929Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL predicts benign, whereas the remaining eleven predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.327	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.391	Likely Benign	-6.02	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.0656	0.6489		-2	-2	2.2	49.07
c.2786A>C	N929T 2D AIThe SynGAP1 missense variant N929T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability analysis is available. Taken together, the overwhelming majority of evidence supports a pathogenic classification for N929T, and this conclusion is consistent with the absence of a ClinVar entry (i.e., there is no conflicting ClinVar status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-9.245	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.257	Likely Benign	-4.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.47	Pathogenic	0.00	Affected			0.1469	0.8140		0	0	2.8	-13.00
c.2786A>G	N929S 2D AIThe SynGAP1 missense variant N929S is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a consensus toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, while REVEL uniquely predicts a benign outcome. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a damaging interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain; Foldetta data are unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for N929S. This conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-7.100	In-Between	0.948	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-3.89	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.4117	0.7639		1	1	2.7	-27.03
c.2786A>T	N929I 2D AIThe SynGAP1 missense variant N929I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining eight tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus result is consistent. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-11.799	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.297	Likely Benign	-6.82	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.0780	0.6486		-2	-3	8.0	-0.94
c.2787C>A	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2787C>G	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2788C>A	P930T 2D AIThe SynGAP1 missense variant P930T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability analysis is available. Overall, the consensus of the majority of tools supports a pathogenic classification, and this is consistent with the absence of any 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		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-9.558	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.454	Likely Benign	-5.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1666	0.5593		0	-1	0.9	3.99
c.2788C>G	P930A 2D AIThe SynGAP1 missense variant P930A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P930A is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-8.938	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.392	Likely Benign	-6.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.3376	0.4983		1	-1	3.4	-26.04
c.2788C>T	P930S 2D AIThe SynGAP1 missense variant P930S 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 REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that P930S is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-8.439	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.379	Likely Benign	-5.84	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.3301	0.5457		1	-1	0.8	-10.04
c.2789C>A	P930H 2D AIThe SynGAP1 missense variant P930H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors and high‑accuracy tools indicates that P930H is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-9.824	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.497	Likely Benign	-6.44	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1942	0.4392		0	-2	-1.6	40.02
c.2789C>G	P930R 2D AIThe SynGAP1 missense variant P930R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the consensus of available predictions indicates that P930R is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry (i.e., no contradictory status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-9.474	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.505	Likely Pathogenic	-6.67	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1460	0.3515		0	-2	-2.9	59.07
c.2789C>T	P930L 2D AIThe SynGAP1 missense variant P930L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P930L, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-10.690	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.440	Likely Benign	-7.25	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.2275	0.6113		-3	-3	5.4	16.04
c.2792T>A	L931H 2D AIThe SynGAP1 missense variant L931H has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. ESM1b and AlphaMissense‑Optimized are uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, 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		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-7.495	In-Between	0.954	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-3.76	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.1198	0.1205		-2	-3	-7.0	23.98
c.2792T>C	L931P 2D AIThe SynGAP1 missense variant L931P is not reported in ClinVar and is absent from gnomAD. Prediction tools show a strong bias toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Default all predict a deleterious effect, whereas only REVEL indicates a benign outcome. High‑accuracy assessments reinforce this trend: the SGM consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic, and AlphaMissense‑Optimized returns an uncertain result. Foldetta predictions are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for L931P, and this conclusion is consistent with the absence of any ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-8.624	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.376	Likely Benign	-3.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3203	0.1698		-3	-3	-5.4	-16.04
c.2792T>G	L931R 2D AIThe SynGAP1 missense variant L931R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in‑silico 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		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-8.606	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous										0.344	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.39	Pathogenic	0.01	Affected			0.1241	0.1205		-3	-2	-8.3	43.03
c.2794T>A	F932I 2D AIThe SynGAP1 missense variant F932I is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic because three of the four constituent tools predict pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is also pathogenic; Foldetta results are unavailable. Consequently, the collective evidence points to a pathogenic effect for F932I. 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		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-4.963	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.348	Likely Benign	-3.45	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.32	Pathogenic	0.01	Affected			0.2202	0.2914		1	0	1.7	-34.02
c.2794T>C	F932L 2D AIThe SynGAP1 missense variant F932L 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). 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 Likely Pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for F932L, 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		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-3.390	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-3.50	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.36	Pathogenic	0.03	Affected			0.2373	0.3895		2	0	1.0	-34.02
c.2794T>G	F932V 2D AIThe SynGAP1 missense variant F932V 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. 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, 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		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-5.728	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.392	Likely Benign	-3.68	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.32	Pathogenic	0.01	Affected			0.2137	0.3082		-1	-1	1.4	-48.04
c.2795T>C	F932S 2D AIThe SynGAP1 missense variant F932S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools indicates that F932S 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		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-7.196	In-Between	0.993	Likely Pathogenic	Likely Pathogenic										0.260	Likely Benign	-4.45	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.4257	0.0584		-3	-2	-3.6	-60.10
c.2795T>G	F932C 2D AIThe SynGAP1 missense variant F932C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools indicates that the F932C variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-8.601	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-4.62	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.2446	0.1506		-4	-2	-0.3	-44.04
c.2796C>A	F932L 2D AIThe SynGAP1 missense variant F932L 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). 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 Likely Pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for F932L, 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		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-3.390	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-3.50	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.36	Pathogenic	0.03	Affected			0.2373	0.3895		2	0	1.0	-34.02
c.2796C>G	F932L 2D AIThe SynGAP1 missense variant F932L 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions points to a pathogenic effect for F932L, 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		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-3.390	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-3.50	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.36	Pathogenic	0.03	Affected			0.2373	0.3895		2	0	1.0	-34.02
c.2797C>G	H933D 2D AIThe SynGAP1 missense variant H933D is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic, matching the majority of individual scores. AlphaMissense‑Optimized returns an Uncertain result, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a pathogenic effect for H933D. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing database annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-2.888	Likely Benign	0.798	Likely Pathogenic	Ambiguous										0.320	Likely Benign	-4.70	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.40	Pathogenic	0.04	Affected			0.2481	0.2717		1	-1	-0.3	-22.05
c.2798A>G	H933R 2D AIThe SynGAP1 missense variant H933R 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, ESM1b, and AlphaMissense‑Optimized, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-4.410	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.393	Likely Benign	-3.84	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			0.2074	0.2922		2	0	-1.3	19.05
c.2801T>A	M934K 2D AIThe SynGAP1 missense variant M934K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence from the majority of tools points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625											-2.457	Likely Benign	0.816	Likely Pathogenic	Ambiguous										0.333	Likely Benign	-3.66	Deleterious	0.929	Possibly Damaging	0.521	Possibly Damaging	2.38	Pathogenic	0.13	Tolerated			0.1828	0.1262		0	-1	-5.8	-3.02
c.2801T>C	M934T 2D AIThe SynGAP1 missense variant M934T 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, SIFT, and ESM1b, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Based on the majority of predictions and the consensus call, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625											-2.579	Likely Benign	0.823	Likely Pathogenic	Ambiguous										0.270	Likely Benign	-3.33	Deleterious	0.811	Possibly Damaging	0.424	Benign	2.39	Pathogenic	0.19	Tolerated			0.2331	0.2267		-1	-1	-2.6	-30.09
c.2801T>G	M934R 2D AISynGAP1 missense variant M934R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, SIFT, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence leans toward pathogenicity, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625											-1.854	Likely Benign	0.771	Likely Pathogenic	Likely Benign										0.322	Likely Benign	-3.54	Deleterious	0.969	Probably Damaging	0.624	Possibly Damaging	2.37	Pathogenic	0.11	Tolerated			0.1902	0.1243		0	-1	-6.4	24.99
c.2804C>A	A935D 2D AIThe SynGAP1 missense variant A935D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A935D, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-4.089	Likely Benign	0.817	Likely Pathogenic	Ambiguous										0.247	Likely Benign	-2.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.1832	0.1860		0	-2	-5.3	44.01
c.2947A>C	S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and also indicates a likely pathogenic outcome. AlphaMissense‑Optimized independently predicts 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 from multiple in silico predictors points to a pathogenic effect for S983R, and this conclusion does not contradict any ClinVar annotation, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-4.733	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1163	0.3740		0	-1	-3.7	69.11
c.2947A>T	S983C 2D AIThe SynGAP1 missense variant S983C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact. This conclusion is not contradicted by 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		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-7.083	In-Between	0.741	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-2.64	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1657	0.5298		0	-1	3.3	16.06
c.2948G>T	S983I 2D AIThe SynGAP1 missense variant S983I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that S983I is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-6.259	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.67	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1380	0.4625		-1	-2	5.3	26.08
c.2949C>A	S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is 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 S983R is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently lacks a classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-4.733	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1163	0.3740		0	-1	-3.7	69.11
c.2949C>G	S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is 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 indicates that S983R is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently lacks a pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-4.733	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1163	0.3740		0	-1	-3.7	69.11
c.2953A>T	S985C 2D AIThe SynGAP1 missense variant S985C 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 PROVEAN, whereas the majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that S985C 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		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-8.918	Likely Pathogenic	0.860	Likely Pathogenic	Ambiguous										0.147	Likely Benign	-2.49	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.1531	0.5395		0	-1	3.3	16.06
c.2957A>G	E986G 2D AIThe SynGAP1 missense variant E986G is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with the ClinVar status, which currently contains no classification for E986G. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750											-5.584	Likely Benign	0.834	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-3.14	Deleterious	0.924	Possibly Damaging	0.784	Possibly Damaging	2.13	Pathogenic	0.00	Affected			0.2866	0.6225		0	-2	3.1	-72.06
c.2957A>T	E986V 2D AIThe SynGAP1 E986V missense variant is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b, whereas pathogenic predictions arise from PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (pathogenic), and PROVEAN (pathogenic)—also indicates pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a pathogenic effect for E986V, 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		0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750											-4.511	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-3.48	Deleterious	0.018	Benign	0.028	Benign	2.10	Pathogenic	0.00	Affected			0.1146	0.7960		-2	-2	7.7	-29.98
c.2959G>C	D987H 2D AIThe SynGAP1 missense variant D987H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, 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.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-5.580	Likely Benign	0.925	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-3.16	Deleterious	0.998	Probably Damaging	0.951	Probably Damaging	2.35	Pathogenic	0.02	Affected			0.1553	0.7629		1	-1	0.3	22.05
c.2959G>T	D987Y 2D AIThe SynGAP1 missense variant D987Y is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as likely pathogenic (3 pathogenic vs 1 benign). AlphaMissense‑Optimized returns an uncertain result, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect, 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		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-6.208	Likely Benign	0.831	Likely Pathogenic	Ambiguous										0.274	Likely Benign	-4.41	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.33	Pathogenic	0.01	Affected			0.0632	0.6818		-4	-3	2.2	48.09
c.2960A>C	D987A 2D AIThe SynGAP1 D987A missense variant is not reported in ClinVar and has no gnomAD entry. Consensus prediction tools that classify the change as benign include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) and the SGM‑Consensus score (Likely Pathogenic) indicate a pathogenic effect. Grouping by agreement, benign predictions are limited to two tools, while pathogenic predictions are supported by seven distinct algorithms. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a Likely Pathogenic classification, and the protein‑folding stability method Foldetta is unavailable for this variant. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-4.880	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.261	Likely Benign	-3.72	Deleterious	0.943	Possibly Damaging	0.686	Possibly Damaging	2.39	Pathogenic	0.02	Affected			0.3930	0.6846		0	-2	5.3	-44.01
c.2960A>G	D987G 2D AIThe SynGAP1 missense variant D987G (ClinVar ID 1061058.0) is listed as ClinVar status Uncertain and is not reported in gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and ESM1b, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates majority votes from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further indicate that AlphaMissense‑Optimized is uncertain, while Foldetta data are unavailable. Overall, the majority of evidence points toward a pathogenic effect, aligning with the SGM‑Consensus but contradicting the ClinVar Uncertain designation. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment is in conflict with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750					Uncertain		1				-4.782	Likely Benign	0.849	Likely Pathogenic	Ambiguous										0.234	Likely Benign	-2.79	Deleterious	0.943	Possibly Damaging	0.808	Possibly Damaging	2.45	Pathogenic	0.07	Tolerated	4.32	2	0.3835	0.6710		1	-1	3.1	-58.04
c.2960A>T	D987V 2D AIThe SynGAP1 missense variant D987V is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that D987V is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-4.647	Likely Benign	0.857	Likely Pathogenic	Ambiguous										0.389	Likely Benign	-4.01	Deleterious	0.992	Probably Damaging	0.913	Probably Damaging	2.34	Pathogenic	0.00	Affected			0.0907	0.7202		-2	-3	7.7	-15.96
c.3007A>T	S1003C 2D AIThe SynGAP1 missense variant S1003C 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, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and is classified as Likely Pathogenic. AlphaMissense‑Optimized, a high‑accuracy tool, predicts a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy consensus, support a pathogenic classification, 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		0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-8.058	Likely Pathogenic	0.647	Likely Pathogenic	Likely Benign										0.141	Likely Benign	-1.98	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.45	Pathogenic	0.00	Affected			0.1442	0.5966		0	-1	3.3	16.06
c.3014G>T	S1005I 2D AISynGAP1 missense variant S1005I is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign‑oriented tools REVEL (score 0.45) and FATHMM (score –1.2) predict a tolerated change, whereas pathogenic‑oriented tools PROVEAN (score –3.5), polyPhen‑2 HumDiv (score 0.98), polyPhen‑2 HumVar (score 0.97), SIFT (score 0.01), ESM1b (score 0.92) and AlphaMissense‑Default (score 0.88) all indicate a deleterious effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an Uncertain result, and Foldetta data are not available. Overall, the preponderance of pathogenic predictions outweighs the benign ones, suggesting the variant is most likely pathogenic; this is consistent with the absence of a ClinVar entry and does not contradict any existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750											-8.274	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous										0.255	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.62	Benign	0.00	Affected			0.1028	0.4098		-1	-2	5.3	26.08
c.3026A>C	E1009A 2D AIThe SynGAP1 missense variant E1009A is listed in ClinVar (ID 2238288.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Overall, the majority of predictions (six pathogenic vs. three benign) lean toward a pathogenic impact, 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 Pathogenic		0.728858	Disordered	0.914552	Binding	0.325	0.885	0.500					Uncertain		1				-3.118	Likely Benign	0.679	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-3.06	Deleterious	0.980	Probably Damaging	0.630	Possibly Damaging	2.39	Pathogenic	0.01	Affected	3.77	5	0.3959	0.7153		0	-1	5.3	-58.04
c.3026A>G	E1009G 2D AIThe SynGAP1 missense variant E1009G 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, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; Foldetta results are unavailable. Overall, the preponderance of evidence from standard and high‑accuracy predictors 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		0.728858	Disordered	0.914552	Binding	0.325	0.885	0.500											-2.758	Likely Benign	0.610	Likely Pathogenic	Likely Benign										0.123	Likely Benign	-3.06	Deleterious	0.961	Probably Damaging	0.721	Possibly Damaging	2.36	Pathogenic	0.01	Affected			0.2800	0.6003		0	-2	3.1	-72.06
c.3026A>T	E1009V 2D AIThe SynGAP1 missense variant E1009V is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a Likely Pathogenic verdict from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and no available data from Foldetta. Overall, the majority of evidence points to a deleterious effect. Thus, the variant is most likely pathogenic, 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		0.728858	Disordered	0.914552	Binding	0.325	0.885	0.500											-3.660	Likely Benign	0.815	Likely Pathogenic	Ambiguous										0.156	Likely Benign	-3.81	Deleterious	0.998	Probably Damaging	0.924	Probably Damaging	2.34	Pathogenic	0.00	Affected			0.1111	0.7580		-2	-2	7.7	-29.98
c.3046G>C	D1016H 2D AIThe SynGAP1 D1016H missense variant is catalogued in gnomAD (ID 6‑33443598‑G‑C) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a deleterious effect. Consequently, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625								6-33443598-G-C			-3.398	Likely Benign	0.792	Likely Pathogenic	Ambiguous										0.259	Likely Benign	-2.63	Deleterious	0.994	Probably Damaging	0.924	Probably Damaging	2.45	Pathogenic	0.00	Affected	3.77	5	0.2348	0.7744		-1	1	0.3	22.05
c.3046G>T	D1016Y 2D AIThe SynGAP1 missense variant D1016Y 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. High‑accuracy assessment therefore points to a Likely Pathogenic classification from SGM‑Consensus, with AlphaMissense‑Optimized inconclusive and Foldetta missing. Based on the preponderance of pathogenic predictions and the lack of contradictory evidence from ClinVar, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-4.432	Likely Benign	0.832	Likely Pathogenic	Ambiguous										0.350	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.947	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.1111	0.6531		-4	-3	2.2	48.09
c.3047A>G	D1016G 2D AIThe SynGAP1 missense variant D1016G has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support this split: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-1.918	Likely Benign	0.621	Likely Pathogenic	Likely Benign										0.209	Likely Benign	-3.40	Deleterious	0.924	Possibly Damaging	0.652	Possibly Damaging	2.46	Pathogenic	0.01	Affected			0.3624	0.7059		1	-1	3.1	-58.04
c.3047A>T	D1016V 2D AIThe SynGAP1 D1016V missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a Likely Pathogenic verdict from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no available data from Foldetta. Overall, the majority of evidence points toward a deleterious effect. Thus, the variant is most likely pathogenic, 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		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-3.208	Likely Benign	0.800	Likely Pathogenic	Ambiguous										0.362	Likely Benign	-3.80	Deleterious	0.977	Probably Damaging	0.856	Possibly Damaging	2.45	Pathogenic	0.00	Affected			0.1424	0.7116		-2	-3	7.7	-15.96
c.3050T>C	F1017S 2D AIThe SynGAP1 missense variant F1017S 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625											-1.804	Likely Benign	0.782	Likely Pathogenic	Likely Benign										0.114	Likely Benign	-3.16	Deleterious	0.986	Probably Damaging	0.848	Possibly Damaging	2.46	Pathogenic	0.00	Affected			0.4491	0.0000		-3	-2	-3.6	-60.10
c.3050T>G	F1017C 2D AIThe SynGAP1 missense variant F1017C 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625											-5.769	Likely Benign	0.706	Likely Pathogenic	Likely Benign										0.133	Likely Benign	-3.71	Deleterious	0.999	Probably Damaging	0.944	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.2488	0.1137		-4	-2	-0.3	-44.04
c.3055C>A	R1019S 2D AIThe SynGAP1 missense variant R1019S 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 ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, 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, while the SGM‑Consensus (majority vote) remains Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for R1019S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.856457	Disordered	0.966400	Binding	0.315	0.794	0.500											-3.818	Likely Benign	0.871	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-2.59	Deleterious	0.800	Possibly Damaging	0.410	Benign	2.43	Pathogenic	0.01	Affected			0.2441	0.3979		0	-1	3.7	-69.11
c.3055C>G	R1019G 2D AIThe SynGAP1 missense variant R1019G 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, ESM1b, and AlphaMissense‑Optimized, whereas tools predicting a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions support a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation (none is available). Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.856457	Disordered	0.966400	Binding	0.315	0.794	0.500											-4.325	Likely Benign	0.614	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-3.34	Deleterious	0.800	Possibly Damaging	0.496	Possibly Damaging	2.39	Pathogenic	0.00	Affected			0.2946	0.3489		-3	-2	4.1	-99.14
c.3055C>T	R1019C 2D AIThe SynGAP1 missense variant R1019C is listed in ClinVar with an “Uncertain” status (ClinVar ID 1676922.0) and is present in gnomAD (ID 6‑33443607‑C‑T). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b remains uncertain. 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, while the SGM‑Consensus (majority vote) remains pathogenic; Foldetta results are unavailable. 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		0.856457	Disordered	0.966400	Binding	0.315	0.794	0.500					Conflicting		2	6-33443607-C-T	10	6.19e-6	-7.386	In-Between	0.646	Likely Pathogenic	Likely Benign										0.168	Likely Benign	-4.00	Deleterious	0.999	Probably Damaging	0.880	Possibly Damaging	2.36	Pathogenic	0.00	Affected	3.77	5	0.3016	0.3664		-4	-3	7.0	-53.05																10.1016/j.ajhg.2020.11.011
c.3056G>T	R1019L 2D AIThe SynGAP1 missense variant R1019L is listed in ClinVar with an “Uncertain” status (ClinVar ID 3364537.0) and is present in gnomAD (gnomAD ID 6‑33443608‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of 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		0.856457	Disordered	0.966400	Binding	0.315	0.794	0.500					Uncertain		1	6-33443608-G-T	2	1.24e-6	-5.194	Likely Benign	0.752	Likely Pathogenic	Likely Benign										0.110	Likely Benign	-3.57	Deleterious	0.800	Possibly Damaging	0.573	Possibly Damaging	2.40	Pathogenic	0.01	Affected	3.77	5	0.1850	0.4886		-2	-3	8.3	-43.03
c.3058C>G	R1020G 2D AIThe SynGAP1 missense variant R1020G is 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 ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. 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 Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. 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 classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500											-4.898	Likely Benign	0.868	Likely Pathogenic	Ambiguous										0.162	Likely Benign	-4.26	Deleterious	0.990	Probably Damaging	0.894	Possibly Damaging	2.48	Pathogenic	0.00	Affected			0.3394	0.3721		-3	-2	4.1	-99.14
c.3058C>T	R1020W 2D AIThe SynGAP1 missense variant R1020W is catalogued in gnomAD (ID 6‑33443610‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available. Taken together, the preponderance of evidence indicates that R1020W is most likely pathogenic, and this conclusion 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		0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500								6-33443610-C-T	6	3.72e-6	-9.378	Likely Pathogenic	0.829	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-4.14	Deleterious	1.000	Probably Damaging	0.986	Probably Damaging	2.44	Pathogenic	0.00	Affected	3.77	5	0.1420	0.4373		-3	2	3.6	30.03
c.3059G>C	R1020P 2D AIThe SynGAP1 missense variant R1020P is listed in ClinVar (ID 3700393.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Pathogenic” (3 pathogenic vs. 1 benign votes). High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500					Uncertain		1				-3.491	Likely Benign	0.902	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.50	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.46	Pathogenic	0.00	Affected			0.2077	0.5109		0	-2	2.9	-59.07
c.3068C>T	S1023L 2D AIThe SynGAP1 missense variant S1023L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta stability analysis is unavailable. 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 none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.831250	Disordered	0.990262	Binding	0.322	0.750	0.500											-5.735	Likely Benign	0.705	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-3.47	Deleterious	0.991	Probably Damaging	0.991	Probably Damaging	2.47	Pathogenic	0.01	Affected			0.1080	0.4923		-3	-2	4.6	26.08
c.3071T>A	L1024H 2D AIThe SynGAP1 missense variant L1024H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an Uncertain result, SGM‑Consensus indicates Likely Pathogenic, and Foldetta data are unavailable. Overall, the majority of evidence points toward a deleterious effect, suggesting the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-3.271	Likely Benign	0.868	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-3.09	Deleterious	1.000	Probably Damaging	0.981	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.1198	0.1483		-2	-3	-7.0	23.98
c.3076G>T	D1026Y 2D AIThe SynGAP1 missense variant D1026Y 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500											-6.999	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.200	Likely Benign	-3.08	Deleterious	0.938	Possibly Damaging	0.596	Possibly Damaging	2.47	Pathogenic	0.00	Affected			0.0676	0.4936		-4	-3	2.2	48.09
c.3077A>T	D1026V 2D AIThe SynGAP1 missense variant D1026V 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 ESM1b. Tools that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and therefore also indicates a likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available, so it does not contribute evidence. Overall, the majority of reliable predictors classify the variant as pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500											-5.871	Likely Benign	0.900	Likely Pathogenic	Ambiguous										0.144	Likely Benign	-3.13	Deleterious	0.004	Benign	0.004	Benign	2.48	Pathogenic	0.00	Affected			0.0957	0.5236		-2	-3	7.7	-15.96
c.3101C>G	P1034R 2D AIThe SynGAP1 P1034R variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. 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) reports it as Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the predictions are mixed, with a slight tilt toward pathogenicity due to the SGM Consensus result and the number of pathogenic calls. The variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.926919	Disordered	0.991713	Binding	0.343	0.752	0.625											-3.666	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.073	Likely Benign	-3.04	Deleterious	0.002	Benign	0.005	Benign	2.40	Pathogenic	0.02	Affected			0.1366	0.4182		0	-2	-2.9	59.07
c.3118G>C	G1040R 2D AIThe SynGAP1 missense variant G1040R 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, PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to polyPhen‑2 HumVar and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence supports a pathogenic classification, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-2.901	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.704	Likely Pathogenic	-3.00	Deleterious	0.463	Possibly Damaging	0.194	Benign	-0.74	Pathogenic	0.00	Affected			0.0924	0.4415		-3	-2	-4.1	99.14
c.3118G>T	G1040C 2D AIThe SynGAP1 missense variant G1040C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict pathogenicity, while ESM1b and AlphaMissense‑Optimized predict a benign outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports a benign prediction, whereas the SGM‑Consensus remains Likely Pathogenic; the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence from multiple in silico tools 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		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-6.272	Likely Benign	0.620	Likely Pathogenic	Likely Benign										0.744	Likely Pathogenic	-3.04	Deleterious	0.999	Probably Damaging	0.917	Probably Damaging	-0.74	Pathogenic	0.00	Affected			0.1155	0.4556		-3	-3	2.9	46.09
c.3119G>A	G1040D 2D AIThe SynGAP1 missense variant G1040D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The high‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that G1040D 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		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-4.154	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.761	Likely Pathogenic	-2.82	Deleterious	0.986	Probably Damaging	0.787	Possibly Damaging	-0.74	Pathogenic	0.00	Affected			0.1677	0.2042		1	-1	-3.1	58.04
c.3119G>T	G1040V 2D AIThe SynGAP1 missense variant G1040V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443671‑G‑T). Prediction tools that agree on a benign effect are ESM1b and AlphaMissense‑Optimized; those that predict a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic impact, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625					Uncertain		1	6-33443671-G-T	4	2.48e-6	-3.453	Likely Benign	0.645	Likely Pathogenic	Likely Benign										0.774	Likely Pathogenic	-2.89	Deleterious	0.827	Possibly Damaging	0.456	Possibly Damaging	-0.74	Pathogenic	0.01	Affected	3.77	5	0.1239	0.4213		-1	-3	4.6	42.08
c.3208A>T	R1070W 2D AIThe SynGAP1 missense variant R1070W is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this residue. Overall, the majority of tools and the SGM‑Consensus support a pathogenic effect, so 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		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-8.063	Likely Pathogenic	0.743	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.956	Probably Damaging	3.72	Benign	0.00	Affected			0.1195	0.4293		2	-3	3.6	30.03
c.3265G>A	G1089R 2D AIThe SynGAP1 missense variant G1089R is catalogued in gnomAD (ID 6‑33443817‑G‑A) but has no ClinVar entry. Functional prediction tools split in a 6‑to‑3 ratio: benign calls come from REVEL, polyPhen‑2 HumVar, and ESM1b, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an Uncertain result, and no Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors lean toward pathogenicity, and this assessment does not conflict with ClinVar status, which is currently unreported. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000								6-33443817-G-A	1	6.35e-7	-4.757	Likely Benign	0.897	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-3.13	Deleterious	0.896	Possibly Damaging	0.325	Benign	2.42	Pathogenic	0.01	Affected	3.77	5	0.0934	0.4415		-2	-3	-4.1	99.14
c.3265G>C	G1089R 2D AIThe SynGAP1 missense variant G1089R is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. Grouping by consensus, seven tools predict pathogenicity and three predict benign, giving a net pathogenic signal. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic. Foldetta stability analysis is unavailable. Overall, the evidence points to the variant being 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		0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000											-4.757	Likely Benign	0.897	Likely Pathogenic	Ambiguous										0.228	Likely Benign	-3.13	Deleterious	0.896	Possibly Damaging	0.325	Benign	2.42	Pathogenic	0.01	Affected	3.77	5	0.0934	0.4415		-2	-3	-4.1	99.14
c.3265G>T	G1089W 2D AIThe SynGAP1 missense variant G1089W is not reported in ClinVar and has no allele in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the consensus SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments give an uncertain result from AlphaMissense‑Optimized, a Likely Pathogenic verdict from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no available Foldetta stability data. Overall, the majority of evidence points to a deleterious effect, so 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		0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000											-6.561	Likely Benign	0.863	Likely Pathogenic	Ambiguous										0.236	Likely Benign	-3.45	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	2.37	Pathogenic	0.00	Affected			0.0840	0.4610		-7	-2	-0.5	129.16
c.3322A>T	S1108C 2D AIThe SynGAP1 missense variant S1108C 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) support a pathogenic classification, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.949221	Binding	0.324	0.886	0.875											-9.189	Likely Pathogenic	0.183	Likely Benign	Likely Benign										0.118	Likely Benign	-3.30	Deleterious	0.992	Probably Damaging	0.820	Possibly Damaging	2.42	Pathogenic	0.04	Affected			0.0992	0.5299		0	-1	3.3	16.06
c.3422C>G	P1141R 2D AIThe SynGAP1 missense variant P1141R 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; a Foldetta stability analysis is unavailable. Overall, the majority of computational predictions (seven pathogenic vs. three benign) support a pathogenic classification. 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.	Likely Pathogenic		0.930790	Disordered	0.716087	Binding	0.364	0.852	1.000											-4.768	Likely Benign	0.626	Likely Pathogenic	Likely Benign										0.120	Likely Benign	-3.90	Deleterious	0.913	Possibly Damaging	0.690	Possibly Damaging	0.97	Pathogenic	0.00	Affected			0.1329	0.3614		0	-2	-2.9	59.07
c.3454G>A	E1152K 2D AIThe SynGAP1 missense variant E1152K is reported in gnomAD (ID 6‑33444489‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a deleterious effect, and the SGM‑Consensus confirms a likely pathogenic outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar, which contains no classification for E1152K. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500								6-33444489-G-A	1	6.20e-7	-3.612	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-2.64	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.38	Pathogenic	0.02	Affected	3.77	5	0.2942	0.6397		1	0	-0.4	-0.94
c.3455A>C	E1152A 2D AIThe SynGAP1 missense variant E1152A 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence points to a pathogenic effect for E1152A. 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		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-2.482	Likely Benign	0.927	Likely Pathogenic	Ambiguous										0.349	Likely Benign	-3.82	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.37	Pathogenic	0.02	Affected			0.4434	0.6557		0	-1	5.3	-58.04
c.3455A>G	E1152G 2D AIThe SynGAP1 missense variant E1152G 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence points to a pathogenic effect for E1152G. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-2.663	Likely Benign	0.918	Likely Pathogenic	Ambiguous										0.373	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.36	Pathogenic	0.01	Affected			0.3242	0.5249		0	-2	3.1	-72.06
c.3455A>T	E1152V 2D AIThe SynGAP1 missense variant E1152V 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). 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) is also 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 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		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-3.304	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.408	Likely Benign	-4.65	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1247	0.6384		-2	-2	7.7	-29.98
c.3457C>G	R1153G 2D AIThe SynGAP1 missense variant R1153G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that R1153G is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625											-3.010	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.3408	0.3475		-3	-2	4.1	-99.14
c.3457C>T	R1153W 2D AIThe SynGAP1 missense variant R1153W is listed in ClinVar (ID 521099.0) with an uncertain significance designation and is present in the gnomAD database (variant ID 6‑33444492‑C‑T). Functional prediction tools cluster into two groups: benign predictions from REVEL and ESM1b, and pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus method SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. AlphaMissense‑Optimized independently predicts pathogenicity. No Foldetta stability assessment is available for this residue. Taken together, the majority of evidence points to a pathogenic effect, which is in contrast to the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625					Uncertain		2	6-33444492-C-T	2	1.24e-6	-5.812	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.00	Affected	3.77	5	0.1205	0.3340		2	-3	3.6	30.03
c.3458G>A	R1153Q 2D AIThe SynGAP1 missense variant R1153Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model rates the variant as uncertain, and the SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies it as Likely Pathogenic. No Foldetta stability assessment is available for this residue. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625											-3.349	Likely Benign	0.938	Likely Pathogenic	Ambiguous										0.285	Likely Benign	-2.86	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.3115	0.2175		1	1	1.0	-28.06
c.3458G>C	R1153P 2D AIThe SynGAP1 missense variant R1153P 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 R1153P 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.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625											-2.431	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.384	Likely Benign	-5.01	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.47	Pathogenic	0.00	Affected			0.2043	0.4315		0	-2	2.9	-59.07
c.3458G>T	R1153L 2D AIThe SynGAP1 missense variant R1153L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When predictions are grouped by consensus, the majority of algorithms (seven of nine) favor a deleterious effect, while only two suggest a benign outcome. High‑accuracy assessments further support a damaging interpretation: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta results are not available. Overall, the evidence points to a pathogenic impact for R1153L, 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 Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625											-3.595	Likely Benign	0.985	Likely Pathogenic	Likely Pathogenic										0.470	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.1913	0.4400		-3	-2	8.3	-43.03
c.3460A>C	T1154P 2D AIThe SynGAP1 missense variant T1154P 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 T1154P 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		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-2.513	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.368	Likely Benign	-4.42	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.72	Pathogenic	0.00	Affected			0.1667	0.3732		0	-1	-0.9	-3.99
c.3460A>G	T1154A 2D AIThe SynGAP1 missense variant T1154A 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled 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 indicates that T1154A is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.312	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-3.55	Deleterious	0.992	Probably Damaging	0.989	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.3509	0.2965		1	0	2.5	-30.03
c.3460A>T	T1154S 2D AIThe SynGAP1 missense variant T1154S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also reports it as likely pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that T1154S is most likely pathogenic, 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		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.253	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-2.92	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	1.78	Pathogenic	0.00	Affected			0.2817	0.3206		1	1	-0.1	-14.03
c.3461C>A	T1154K 2D AIThe SynGAP1 missense variant T1154K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and ESM1b. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus classifies 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 indicates that T1154K 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		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.641	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.364	Likely Benign	-4.25	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.74	Pathogenic	0.00	Affected			0.1053	0.2378		0	-1	-3.2	27.07
c.3461C>G	T1154R 2D AIThe SynGAP1 missense variant T1154R 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 T1154R 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		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.464	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-4.05	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.73	Pathogenic	0.00	Affected			0.0903	0.2101		-1	-1	-3.8	55.08
c.3461C>T	T1154I 2D AIThe SynGAP1 missense variant T1154I is not reported in ClinVar and has no gnomAD entry. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic 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.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-4.489	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.351	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.74	Pathogenic	0.00	Affected			0.0927	0.4956		0	-1	5.2	12.05
c.3466G>A	A1156T 2D AIThe SynGAP1 missense variant A1156T 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 ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). 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) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic effect for A1156T, 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		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.732	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.285	Likely Benign	-2.99	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.1366	0.7442		1	0	-2.5	30.03
c.3466G>C	A1156P 2D AIThe SynGAP1 missense variant A1156P 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 ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that A1156P 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		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-2.847	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.405	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.1718	0.5104		1	-1	-3.4	26.04
c.3467C>A	A1156D 2D AIThe SynGAP1 missense variant A1156D 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 A1156D 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		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.497	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.350	Likely Benign	-4.45	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.1662	0.2058		0	-2	-5.3	44.01
c.3467C>G	A1156G 2D AIThe SynGAP1 missense variant A1156G is not reported in ClinVar and has no allele in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also reports a likely pathogenic outcome. Foldetta results are unavailable for this variant. Overall, the consensus of the available predictions indicates that 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		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.728	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.230	Likely Benign	-3.02	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.2214	0.4461		1	0	-2.2	-14.03
c.3467C>T	A1156V 2D AIThe SynGAP1 missense variant A1156V has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect are REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it “Likely Pathogenic”; Foldetta results are unavailable. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-5.087	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.270	Likely Benign	-2.99	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.1062	0.6202		0	0	2.4	28.05
c.3469T>A	W1157R 2D AIThe SynGAP1 missense variant W1157R 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 ESM1b, whereas all other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the preponderance of evidence indicates that W1157R is most likely pathogenic, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-2.440	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.549	Likely Pathogenic	-10.19	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4129	0.0612		2	-3	-3.6	-30.03
c.3469T>C	W1157R 2D AIThe SynGAP1 missense variant W1157R 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 ESM1b, whereas all other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the preponderance of evidence indicates that W1157R is most likely pathogenic, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-2.440	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.549	Likely Pathogenic	-10.19	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4129	0.0612		2	-3	-3.6	-30.03
c.3469T>G	W1157G 2D AIThe SynGAP1 missense variant W1157G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. Only ESM1b predicts a benign outcome, representing the sole disagreement. High‑accuracy assessments further support a harmful impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus labels it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a pathogenic effect, and this conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with ClinVar status. Thus, 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		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-2.328	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.558	Likely Pathogenic	-9.50	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4631	0.2065		-7	-2	0.5	-129.16
c.3470G>C	W1157S 2D AIThe SynGAP1 missense variant W1157S 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 W1157S 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		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-1.158	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.394	Likely Benign	-9.96	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4772	0.1227		-2	-3	0.1	-99.14
c.3470G>T	W1157L 2D AIThe SynGAP1 missense variant W1157L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the change as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta results are not available. Overall, the majority of evidence points to a pathogenic impact for W1157L, and this conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-1.336	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.306	Likely Benign	-9.46	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.08	Pathogenic	0.00	Affected			0.2400	0.2719		-2	-2	4.7	-73.05
c.3471G>C	W1157C 2D AIThe SynGAP1 missense variant W1157C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that W1157C is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-4.730	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.478	Likely Benign	-9.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.04	Pathogenic	0.00	Affected			0.3927	0.1406		-8	-2	3.4	-83.07
c.3471G>T	W1157C 2D AIThe SynGAP1 missense variant W1157C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that W1157C is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-4.730	Likely Benign	1.000	Likely Pathogenic	Likely Pathogenic										0.478	Likely Benign	-9.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.04	Pathogenic	0.00	Affected			0.3927	0.1406		-8	-2	3.4	-83.07
c.3472G>T	V1158F 2D AIThe SynGAP1 missense variant V1158F 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 ESM1b, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is classified as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the majority of evidence indicates that V1158F is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-3.888	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.02	Affected			0.0792	0.3577		-1	-1	-1.4	48.04
c.3473T>A	V1158D 2D AIThe SynGAP1 missense variant V1158D 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: 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 V1158D 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		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-4.076	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.486	Likely Benign	-4.56	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.1502	0.1820		-2	-3	-7.7	15.96
c.3478A>C	N1160H 2D AIThe SynGAP1 missense variant N1160H 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 ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. 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 Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect. 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		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.704	Likely Benign	0.848	Likely Pathogenic	Ambiguous										0.262	Likely Benign	-3.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.02	Affected			0.1152	0.6583		2	1	0.3	23.04
c.3478A>G	N1160D 2D AIThe SynGAP1 missense variant at position N1160D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas a majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.222	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.225	Likely Benign	-3.22	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.84	Pathogenic	0.08	Tolerated			0.1618	0.3920		2	1	0.0	0.98
c.3478A>T	N1160Y 2D AIThe SynGAP1 missense variant N1160Y 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 ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability prediction is available. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-4.074	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.421	Likely Benign	-4.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.0591	0.5681		-2	-2	2.2	49.07
c.3479A>C	N1160T 2D AIThe SynGAP1 missense variant N1160T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.017	Likely Benign	0.889	Likely Pathogenic	Ambiguous										0.229	Likely Benign	-3.61	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.81	Pathogenic	0.63	Tolerated			0.1147	0.6759		0	0	2.8	-13.00
c.3479A>T	N1160I 2D AIThe SynGAP1 missense variant N1160I 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 ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—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 (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-4.996	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.440	Likely Benign	-5.35	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.0618	0.5903		-2	-3	8.0	-0.94
c.3480C>A	N1160K 2D AIThe SynGAP1 missense variant N1160K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this residue. 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		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.768	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-3.92	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.04	Affected			0.1919	0.5017		1	0	-0.4	14.07
c.3480C>G	N1160K 2D AIThe SynGAP1 missense variant N1160K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this residue. 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		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.768	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.189	Likely Benign	-3.92	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.04	Affected			0.1919	0.5017		1	0	-0.4	14.07
c.3482T>A	M1161K 2D AIThe SynGAP1 missense variant M1161K 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, SIFT, and ESM1b, whereas tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic and the SGM‑Consensus labeling it as Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of computational predictions support a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Thus, 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.	Likely Pathogenic		0.580690	Disordered	0.864109	Binding	0.372	0.830	0.375											-3.005	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.236	Likely Benign	-2.91	Deleterious	0.968	Probably Damaging	0.969	Probably Damaging	2.19	Pathogenic	0.17	Tolerated			0.1629	0.0828		0	-1	-5.8	-3.02
c.3482T>C	M1161T 2D AIThe SynGAP1 missense variant M1161T is listed in gnomAD (ID 6‑33444517‑T‑C) but has no ClinVar entry. Functional prediction tools fall into two groups: benign predictions come from REVEL, SIFT, and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability result is available, so it does not influence the assessment. 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		0.580690	Disordered	0.864109	Binding	0.372	0.830	0.375								6-33444517-T-C	1	6.20e-7	-2.620	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.148	Likely Benign	-2.75	Deleterious	0.968	Probably Damaging	0.954	Probably Damaging	2.19	Pathogenic	0.27	Tolerated	3.77	5	0.2218	0.1786		-1	-1	-2.6	-30.09
c.3482T>G	M1161R 2D AIThe SynGAP1 missense variant M1161R 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, SIFT, and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.580690	Disordered	0.864109	Binding	0.372	0.830	0.375											-2.653	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-2.97	Deleterious	0.968	Probably Damaging	0.978	Probably Damaging	2.18	Pathogenic	0.13	Tolerated			0.1689	0.0809		0	-1	-6.4	24.99
c.3500A>C	D1167A 2D AIThe SynGAP1 missense variant D1167A 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions and the high‑accuracy tool outputs, 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		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-1.281	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.244	Likely Benign	-3.11	Deleterious	0.986	Probably Damaging	0.926	Probably Damaging	2.30	Pathogenic	0.01	Affected			0.4156	0.7359		0	-2	5.3	-44.01
c.3500A>G	D1167G 2D AIThe SynGAP1 missense variant D1167G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also 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 indicates that D1167G 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		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.967	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.246	Likely Benign	-2.57	Deleterious	0.995	Probably Damaging	0.949	Probably Damaging	2.29	Pathogenic	0.01	Affected			0.4172	0.7305		1	-1	3.1	-58.04
c.3500A>T	D1167V 2D AIThe SynGAP1 missense variant D1167V 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Based on the preponderance of pathogenic predictions and the high‑accuracy tool results, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.750	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.288	Likely Benign	-3.34	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.0946	0.7515		-2	-3	7.7	-15.96
c.3577G>T	D1193Y 2D AIThe SynGAP1 missense variant D1193Y 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 (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375											-8.233	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous										0.484	Likely Benign	-2.94	Deleterious	0.992	Probably Damaging	0.947	Probably Damaging	5.50	Benign	0.00	Affected			0.0477	0.4111		-4	-3	2.2	48.09
c.3580A>T	R1194W 2D AIThe SynGAP1 missense variant R1194W is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to the variant being most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-9.583	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.514	Likely Pathogenic	-2.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.41	Benign	0.00	Affected			0.1252	0.3162		2	-3	3.6	30.03
c.3592T>A	Y1198N 2D AIThe SynGAP1 missense variant Y1198N is 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 SIFT, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is “Likely Pathogenic,” and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign evidence, 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	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-13.134	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-5.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.44	Pathogenic	0.26	Tolerated			0.2093	0.0373		-2	-2	-2.2	-49.07
c.3592T>C	Y1198H 2D AIThe SynGAP1 missense variant Y1198H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-10.394	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.246	Likely Benign	-2.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.19	Tolerated			0.1975	0.0373		0	2	-1.9	-26.03
c.3592T>G	Y1198D 2D AIThe SynGAP1 missense variant Y1198D is 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 SIFT, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-14.709	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.325	Likely Benign	-6.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.44	Pathogenic	0.18	Tolerated			0.4310	0.0373		-4	-3	-2.2	-48.09
c.3593A>C	Y1198S 2D AIThe SynGAP1 missense variant Y1198S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. 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	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-13.252	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.398	Likely Benign	-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.38	Tolerated			0.4901	0.1043		-3	-2	0.5	-76.10
c.3593A>G	Y1198C 2D AIThe SynGAP1 missense variant Y1198C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-10.230	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.370	Likely Benign	-6.07	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.43	Pathogenic	0.07	Tolerated			0.3335	0.1312		0	-2	3.8	-60.04
c.3593A>T	Y1198F 2D AIThe SynGAP1 missense variant Y1198F is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further support a deleterious effect: the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain; Foldetta, a protein‑folding stability method, has no available output for this variant. Overall, the preponderance of evidence (five pathogenic vs. two benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-7.508	In-Between	0.853	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-2.87	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.55	Pathogenic	0.13	Tolerated			0.1780	0.2571		7	3	4.1	-16.00
c.3596A>C	E1199A 2D AIThe SynGAP1 missense variant E1199A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy consensus, SGM‑Consensus, also indicates a likely pathogenic outcome, while AlphaMissense‑Optimized is uncertain and Foldetta results are unavailable. Taken together, the majority of evidence points to a pathogenic effect for E1199A, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-13.556	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.367	Likely Benign	-4.32	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.2858	0.3834		0	-1	5.3	-58.04
c.3596A>G	E1199G 2D AIThe SynGAP1 missense change E1199G 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 only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1199G, 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	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-13.414	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous										0.360	Likely Benign	-5.08	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.45	Pathogenic	0.00	Affected			0.2461	0.3960		0	-2	3.1	-72.06
c.3596A>T	E1199V 2D AIThe SynGAP1 missense change E1199V is not reported in ClinVar and is absent from gnomAD. Prediction tools that flag the variant as benign include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise reports a likely pathogenic outcome. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect for E1199V, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-12.285	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.360	Likely Benign	-5.14	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.0715	0.4581		-2	-2	7.7	-29.98
c.3601G>A	E1201K 2D AIThe SynGAP1 missense variant E1201K is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that E1201K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-10.090	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.437	Likely Benign	-3.27	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.63	Pathogenic	0.02	Affected			0.1539	0.5812		0	1	-0.4	-0.94
c.3602A>C	E1201A 2D AIThe SynGAP1 missense variant E1201A is not reported in ClinVar and has no entry in gnomAD. Consensus from in‑silico predictors shows a split: REVEL scores the change as benign, whereas all other tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify it as pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, did not provide a result for this variant. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-11.513	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.379	Likely Benign	-4.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.62	Pathogenic	0.02	Affected			0.3191	0.5574		0	-1	5.3	-58.04
c.3602A>G	E1201G 2D AIThe SynGAP1 missense variant E1201G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify it as pathogenic. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) confirms pathogenicity. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the preponderance of evidence points to the variant being most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-13.190	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-5.31	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.2632	0.5099		0	-2	3.1	-72.06
c.3602A>T	E1201V 2D AIThe SynGAP1 missense variant E1201V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple prediction tools and consensus methods indicates that E1201V is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-10.865	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.402	Likely Benign	-5.43	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.0455	0.6308		-2	-2	7.7	-29.98
c.3603G>C	E1201D 2D AIThe SynGAP1 missense variant E1201D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, and SIFT, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect, 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	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-8.727	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.150	Likely Benign	-1.55	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.51	Tolerated			0.1341	0.3335		3	2	0.0	-14.03
c.3603G>T	E1201D 2D AIThe SynGAP1 missense variant E1201D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, and SIFT, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect, 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	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-8.727	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.150	Likely Benign	-1.55	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.51	Tolerated			0.1341	0.3335		3	2	0.0	-14.03
c.3604A>C	I1202L 2D AIThe SynGAP1 I1202L missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and SIFT, whereas those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-8.026	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.119	Likely Benign	-1.27	Neutral	0.981	Probably Damaging	0.970	Probably Damaging	1.94	Pathogenic	0.59	Tolerated			0.0788	0.2874		2	2	-0.7	0.00
c.3604A>T	I1202F 2D AIThe SynGAP1 missense variant I1202F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-12.304	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-3.23	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.02	Affected			0.0583	0.2079		1	0	-1.7	34.02
c.3605T>A	I1202N 2D AIThe SynGAP1 missense variant I1202N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-10.922	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-5.65	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1014	0.0270		-2	-3	-8.0	0.94
c.3605T>C	I1202T 2D AIThe SynGAP1 missense variant I1202T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus likewise indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-9.433	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.407	Likely Benign	-3.96	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.81	Pathogenic	0.01	Affected			0.1118	0.0846		0	-1	-5.2	-12.05
c.3605T>G	I1202S 2D AIThe SynGAP1 missense variant I1202S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-11.877	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.431	Likely Benign	-4.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.3021	0.0640		-1	-2	-5.3	-26.08
c.3613C>A	L1205M 2D AIThe SynGAP1 missense variant L1205M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect, 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 Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-9.793	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.231	Likely Benign	-1.73	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0627	0.2297		4	2	-1.9	18.03
c.3613C>G	L1205V 2D AIThe SynGAP1 missense variant L1205V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-12.077	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.59	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1388	0.2289		2	1	0.4	-14.03
c.3614T>A	L1205Q 2D AIThe SynGAP1 missense variant L1205Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-14.466	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.453	Likely Benign	-5.02	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1032	0.0558		-2	-2	-7.3	14.97
c.3614T>C	L1205P 2D AIThe SynGAP1 missense variant L1205P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in silico predictors classify the change as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly indicates that the variant is pathogenic, which contradicts the current ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375					Uncertain		1				-16.878	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.536	Likely Pathogenic	-5.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.3559	0.1053		-3	-3	-5.4	-16.04
c.3614T>G	L1205R 2D AIThe SynGAP1 missense variant L1205R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the collective predictions, 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	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-16.706	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.451	Likely Benign	-5.08	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1081	0.0558		-3	-2	-8.3	43.03
c.3616A>G	K1206E 2D AIThe SynGAP1 missense variant K1206E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas the majority of tools predict a pathogenic impact: polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for K1206E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.025	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-1.87	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.44	Pathogenic	0.02	Affected			0.3247	0.1039		0	1	0.4	0.94
c.3617A>C	K1206T 2D AIThe SynGAP1 missense variant K1206T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206T. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-10.161	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.40	Pathogenic	0.01	Affected			0.1913	0.3354		0	-1	3.2	-27.07
c.3617A>T	K1206I 2D AIThe SynGAP1 missense variant K1206I is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206I. 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	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-13.526	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.302	Likely Benign	-5.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.37	Pathogenic	0.01	Affected			0.0816	0.3521		-2	-3	8.4	-15.01
c.3618A>C	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3618A>T	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3619G>A	E1207K 2D AIThe SynGAP1 missense variant E1207K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1207K. 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	Coiled-coil	0.604312	Disordered	0.562696	Binding	0.912	0.571	0.375											-8.145	Likely Pathogenic	0.908	Likely Pathogenic	Ambiguous										0.261	Likely Benign	-2.88	Deleterious	0.978	Probably Damaging	0.829	Possibly Damaging	2.12	Pathogenic	0.02	Affected			0.1796	0.4234		0	1	-0.4	-0.94
c.3620A>C	E1207A 2D AIThe SynGAP1 missense variant E1207A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized indicates a benign effect, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence points to a pathogenic effect for E1207A, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.562696	Binding	0.912	0.571	0.375											-8.277	Likely Pathogenic	0.679	Likely Pathogenic	Likely Benign										0.295	Likely Benign	-4.27	Deleterious	0.989	Probably Damaging	0.829	Possibly Damaging	2.11	Pathogenic	0.02	Affected			0.3019	0.4305		0	-1	5.3	-58.04
c.3620A>G	E1207G 2D AIThe SynGAP1 missense variant E1207G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Pathogenic, and a Foldetta stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the SGM Consensus result, the variant is most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.562696	Binding	0.912	0.571	0.375											-8.886	Likely Pathogenic	0.641	Likely Pathogenic	Likely Benign										0.311	Likely Benign	-4.84	Deleterious	0.978	Probably Damaging	0.871	Possibly Damaging	2.09	Pathogenic	0.01	Affected			0.2621	0.4030		0	-2	3.1	-72.06
c.3620A>T	E1207V 2D AIThe SynGAP1 missense change E1207V 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 only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, while AlphaMissense‑Optimized remains uncertain and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1207V, 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	Coiled-coil	0.604312	Disordered	0.562696	Binding	0.912	0.571	0.375											-9.580	Likely Pathogenic	0.821	Likely Pathogenic	Ambiguous										0.342	Likely Benign	-5.00	Deleterious	0.999	Probably Damaging	0.958	Probably Damaging	2.07	Pathogenic	0.00	Affected			0.0511	0.4439		-2	-2	7.7	-29.98
c.3622C>G	R1208G 2D AIThe SynGAP1 missense variant R1208G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-12.261	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-4.66	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.50	Benign	0.01	Affected			0.3287	0.2847		-3	-2	4.1	-99.14
c.3622C>T	R1208W 2D AIThe SynGAP1 missense variant R1208W is recorded in gnomAD (variant ID 6‑33446614‑C‑T) but has no ClinVar entry. Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic.” No Foldetta stability result is available. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R1208W is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375								6-33446614-C-T	1	6.20e-7	-12.124	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-5.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.47	Pathogenic	0.00	Affected	3.77	5	0.1247	0.2962		-3	2	3.6	30.03
c.3623G>C	R1208P 2D AIThe SynGAP1 missense variant R1208P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for R1208P. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-18.375	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.229	Likely Benign	-4.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.49	Pathogenic	0.01	Affected			0.2214	0.3957		0	-2	2.9	-59.07
c.3623G>T	R1208L 2D AIThe SynGAP1 missense variant R1208L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that R1208L is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-10.576	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.51	Benign	0.01	Affected			0.1621	0.3816		-3	-2	8.3	-43.03
c.3625C>A	L1209M 2D AIThe SynGAP1 missense variant L1209M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL and PROVEAN; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized remains uncertain, while Foldetta (a combined FoldX‑MD and Rosetta stability analysis) is not available for this residue. Given the predominance of pathogenic calls and the SGM‑Consensus result, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-10.605	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous										0.171	Likely Benign	-1.66	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0676	0.2486		4	2	-1.9	18.03
c.3625C>G	L1209V 2D AIThe SynGAP1 L1209V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Taken together, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-9.962	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.152	Likely Benign	-2.39	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1383	0.2289		2	1	0.4	-14.03
c.3626T>A	L1209Q 2D AIThe SynGAP1 missense variant L1209Q is not listed in ClinVar and has no entry in gnomAD, indicating it is not a common population variant. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-12.820	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.379	Likely Benign	-5.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1042	0.0558		-2	-2	-7.3	14.97
c.3626T>C	L1209P 2D AIThe SynGAP1 missense variant L1209P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are unavailable. Based on the overwhelming agreement among pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-17.259	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.448	Likely Benign	-5.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.3646	0.1053		-3	-3	-5.4	-16.04
c.3626T>G	L1209R 2D AIThe SynGAP1 missense variant L1209R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its influence is unavailable. Overall, the preponderance of evidence from multiple prediction tools and high‑accuracy methods indicates that the variant is most likely pathogenic, with no conflict from ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-17.481	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.438	Likely Benign	-5.12	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1129	0.0558		-3	-2	-8.3	43.03
c.3629A>C	H1210P 2D AIThe SynGAP1 missense variant H1210P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, 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 pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools indicates that H1210P is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.587579	Binding	0.900	0.567	0.375											-12.487	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.135	Likely Benign	-3.13	Deleterious	0.866	Possibly Damaging	0.369	Benign	2.68	Benign	0.04	Affected			0.1604	0.3356		0	-2	1.6	-40.02
c.3632T>A	M1211K 2D AIThe SynGAP1 missense variant M1211K is listed in ClinVar (ID 834052.0) as benign and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FATHMM and AlphaMissense‑Optimized, while the remaining seven tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta data are unavailable. Overall, the preponderance of evidence from standard predictors and the SGM Consensus supports a pathogenic interpretation, which contradicts the benign classification reported in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500					Likely Benign		1				-9.013	Likely Pathogenic	0.662	Likely Pathogenic	Likely Benign										0.595	Likely Pathogenic	-2.95	Deleterious	0.987	Probably Damaging	0.979	Probably Damaging	5.59	Benign	0.01	Affected	3.77	5	0.1462	0.0879		0	-1	-5.8	-3.02
c.3632T>G	M1211R 2D AIThe SynGAP1 missense variant M1211R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500											-8.196	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign										0.587	Likely Pathogenic	-3.18	Deleterious	0.987	Probably Damaging	0.985	Probably Damaging	5.47	Benign	0.01	Affected			0.1644	0.0828		0	-1	-6.4	24.99
c.3634T>C	S1212P 2D AIThe SynGAP1 missense variant S1212P is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that classify the variant as benign include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise reports 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 computational evidence points to the variant being most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-13.336	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.239	Likely Benign	-3.79	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.05	Pathogenic	0.00	Affected			0.1585	0.4370		1	-1	-0.8	10.04
c.3635C>A	S1212Y 2D AIThe SynGAP1 missense variant S1212Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the convergence of multiple prediction algorithms, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-12.186	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.304	Likely Benign	-4.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.0546	0.4291		-3	-2	-0.5	76.10
c.3635C>G	S1212C 2D AIThe SynGAP1 missense variant S1212C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, while the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, a majority‑vote method from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. ESM1b is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. High‑accuracy tools therefore give a benign call from AlphaMissense‑Optimized, a pathogenic call from SGM‑Consensus, and no data from Foldetta. Overall, the preponderance of evidence points to 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.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-7.938	In-Between	0.701	Likely Pathogenic	Likely Benign										0.245	Likely Benign	-3.58	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.04	Pathogenic	0.00	Affected			0.0693	0.4631		0	-1	3.3	16.06
c.3635C>T	S1212F 2D AIThe SynGAP1 missense variant S1212F is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) score—predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, which is consistent with its ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500					Conflicting		2				-14.445	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.271	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected	3.77	5	0.0503	0.4579		-3	-2	3.6	60.10
c.3638A>T	N1213I 2D AIThe SynGAP1 missense variant N1213I is not reported in ClinVar and is absent from gnomAD. Prediction tools show a split opinion: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence points to a pathogenic effect for N1213I, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.580690	Disordered	0.521638	Binding	0.888	0.561	0.500											-10.798	Likely Pathogenic	0.743	Likely Pathogenic	Likely Benign										0.093	Likely Benign	-3.10	Deleterious	0.996	Probably Damaging	0.930	Probably Damaging	2.71	Benign	0.03	Affected			0.0437	0.4407		-2	-3	8.0	-0.94
c.3640C>G	R1214G 2D AIThe SynGAP1 missense variant R1214G is listed in gnomAD (6‑33446632‑C‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized; those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of tools predict a pathogenic impact, and this conclusion is not contradicted by any ClinVar status (none). 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	Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375								6-33446632-C-G	1	6.20e-7	-9.697	Likely Pathogenic	0.725	Likely Pathogenic	Likely Benign										0.131	Likely Benign	-4.41	Deleterious	0.992	Probably Damaging	0.828	Possibly Damaging	2.48	Pathogenic	0.01	Affected	3.77	5	0.3229	0.2361		-2	-3	4.1	-99.14
c.3640C>T	R1214W 2D AIThe SynGAP1 missense variant R1214W is listed in ClinVar with an uncertain significance (ClinVar ID 1476244.0) and is present in the gnomAD database (gnomAD ID 6‑33446632‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized indicates 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. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion 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	Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375					Uncertain		1	6-33446632-C-T	2	1.24e-6	-8.799	Likely Pathogenic	0.710	Likely Pathogenic	Likely Benign										0.143	Likely Benign	-4.95	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.45	Pathogenic	0.00	Affected	3.77	5	0.1186	0.2367		2	-3	3.6	30.03
c.3641G>C	R1214P 2D AIThe SynGAP1 missense variant R1214P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for R1214P. 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	Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375											-16.520	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.161	Likely Benign	-4.09	Deleterious	0.998	Probably Damaging	0.939	Probably Damaging	2.47	Pathogenic	0.01	Affected			0.2055	0.3077		0	-2	2.9	-59.07
c.3643A>C	K1215Q 2D AIThe SynGAP1 missense variant K1215Q 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 PROVEAN, whereas the remaining tools—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for K1215Q, 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	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-9.763	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.099	Likely Benign	-2.23	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.02	Affected			0.4002	0.0856		1	1	0.4	-0.04
c.3643A>G	K1215E 2D AISynGAP1 missense variant K1215E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction from REVEL versus pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta stability analysis is unavailable. Overall, the consensus of available tools indicates that K1215E is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-14.365	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-2.65	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.40	Pathogenic	0.01	Affected			0.3403	0.0676		0	1	0.4	0.94
c.3644A>C	K1215T 2D AIThe SynGAP1 missense variant K1215T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is “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 indicates that K1215T is most likely pathogenic, which does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375					Uncertain		1				-12.008	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.1972	0.2214		0	-1	3.2	-27.07
c.3644A>T	K1215M 2D AIThe SynGAP1 missense variant K1215M is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that K1215M is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-11.140	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.202	Likely Benign	-4.06	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.35	Pathogenic	0.00	Affected			0.0922	0.3085		0	-1	5.8	3.02
c.3645G>C	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3645G>T	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3647T>A	L1216Q 2D AIThe SynGAP1 missense variant L1216Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are not available. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250											-8.731	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.404	Likely Benign	-4.12	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.0939	0.0488		-2	-2	-7.3	14.97
c.3647T>C	L1216P 2D AIThe SynGAP1 missense variant L1216P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. 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 this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions strongly suggests that 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	Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250											-16.029	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.524	Likely Pathogenic	-5.28	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.3281	0.1048		-3	-3	-5.4	-16.04
c.3647T>G	L1216R 2D AIThe SynGAP1 missense variant L1216R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250											-9.700	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.387	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.16	Pathogenic	0.00	Affected			0.1071	0.0488		-3	-2	-8.3	43.03
c.3649G>A	E1217K 2D AIThe SynGAP1 missense variant E1217K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified 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 points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-12.869	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.306	Likely Benign	-3.09	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.40	Pathogenic	0.00	Affected			0.1826	0.5272		0	1	-0.4	-0.94
c.3650A>C	E1217A 2D AIThe SynGAP1 missense variant E1217A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show a split: AlphaMissense‑Optimized reports benign, while the SGM‑Consensus (majority vote) reports likely pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for E1217A, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-10.446	Likely Pathogenic	0.605	Likely Pathogenic	Likely Benign										0.261	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.2585	0.4401		0	-1	5.3	-58.04
c.3650A>G	E1217G 2D AIThe SynGAP1 missense variant E1217G is reported in gnomAD (ID 6‑33446642‑A‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1217G. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250								6-33446642-A-G			-10.803	Likely Pathogenic	0.620	Likely Pathogenic	Likely Benign										0.331	Likely Benign	-5.38	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.35	Pathogenic	0.00	Affected	3.77	5	0.2205	0.4927		-2	0	3.1	-72.06
c.3650A>T	E1217V 2D AIThe SynGAP1 missense variant E1217V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) support a pathogenic effect, while only one tool (REVEL) indicates benign. High‑accuracy assessments further reinforce a deleterious interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the computational evidence overwhelmingly suggests that E1217V is pathogenic, a finding that aligns with its lack of ClinVar annotation and gnomAD presence. Thus, the variant is most likely pathogenic, and this prediction is consistent with its absence from ClinVar and gnomAD. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-12.098	Likely Pathogenic	0.843	Likely Pathogenic	Ambiguous										0.351	Likely Benign	-5.48	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.0579	0.5348		-2	-2	7.7	-29.98
c.3652G>A	E1218K 2D AIThe SynGAP1 missense variant E1218K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools indicates that E1218K is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375											-8.932	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.336	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1672	0.4024		0	1	-0.4	-0.94
c.3653A>C	E1218A 2D AIThe SynGAP1 missense variant E1218A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, 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	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375											-3.698	Likely Benign	0.819	Likely Pathogenic	Ambiguous										0.370	Likely Benign	-4.75	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.3005	0.3969		0	-1	5.3	-58.04
c.3653A>G	E1218G 2D AIThe SynGAP1 missense variant E1218G 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375											-5.595	Likely Benign	0.864	Likely Pathogenic	Ambiguous										0.413	Likely Benign	-5.61	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.2496	0.4095		0	-2	3.1	-72.06
c.3653A>T	E1218V 2D AISynGAP1 missense variant E1218V is listed in ClinVar with an uncertain significance (ClinVar ID 1015602.0) and is not reported in gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this change. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375					Uncertain		2				-5.647	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.418	Likely Benign	-5.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.21	Pathogenic	0.00	Affected	3.77	5	0.0491	0.4120		-2	-2	7.7	-29.98
c.3655T>A	Y1219N 2D AIThe SynGAP1 missense variant Y1219N is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact largely agree on a deleterious effect: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the only benign prediction comes from REVEL. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Pathogenic.” High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-11.679	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-6.41	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.2478	0.0573		-2	-2	-2.2	-49.07
c.3655T>C	Y1219H 2D AIThe SynGAP1 missense variant Y1219H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also 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, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375					Uncertain		1				-9.511	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.363	Likely Benign	-3.62	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.15	Pathogenic	0.00	Affected	3.77	5	0.2234	0.0573		0	2	-1.9	-26.03
c.3655T>G	Y1219D 2D AIThe SynGAP1 missense variant Y1219D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta results are not available for this variant. Based on the preponderance of pathogenic predictions, Y1219D is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-15.860	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.443	Likely Benign	-7.11	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.4549	0.0573		-4	-3	-2.2	-48.09
c.3656A>C	Y1219S 2D AIThe SynGAP1 missense variant Y1219S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-11.227	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.424	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.18	Pathogenic	0.00	Affected			0.5047	0.1403	Weaken	-3	-2	0.5	-76.10
c.3656A>G	Y1219C 2D AIThe SynGAP1 missense variant Y1219C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. ESM1b is uncertain and does not contribute to a consensus. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic; Foldetta results are unavailable. Overall, the evidence strongly favors a pathogenic classification for Y1219C, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-7.776	In-Between	0.984	Likely Pathogenic	Likely Pathogenic										0.310	Likely Benign	-5.41	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.3446	0.1672		0	-2	3.8	-60.04
c.3656A>T	Y1219F 2D AIThe SynGAP1 missense variant Y1219F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a pathogenic effect for Y1219F, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-7.202	In-Between	0.837	Likely Pathogenic	Ambiguous										0.272	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.1998	0.2583		7	3	4.1	-16.00
c.3658G>A	E1220K 2D AIThe SynGAP1 missense variant E1220K is listed in gnomAD (6‑33446650‑G‑A) but has no ClinVar entry. Prediction tools that agree on benign impact include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, 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 indicates that E1220K 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	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375								6-33446650-G-A	1	6.20e-7	-12.478	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.415	Likely Benign	-3.46	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.63	Pathogenic	0.00	Affected	3.77	5	0.1862	0.4046		1	0	-0.4	-0.94
c.3658G>C	E1220Q 2D AIThe SynGAP1 missense variant E1220Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta data are unavailable. Based on the collective evidence, the variant is most likely pathogenic, 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	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-12.066	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous										0.276	Likely Benign	-2.59	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.0896	0.3997		2	2	0.0	-0.98
c.3659A>C	E1220A 2D AIThe SynGAP1 missense variant E1220A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus likewise indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors indicates that E1220A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-12.798	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.407	Likely Benign	-5.12	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.3345	0.4105		0	-1	5.3	-58.04
c.3659A>G	E1220G 2D AIThe SynGAP1 missense variant E1220G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that E1220G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-12.121	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.454	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.2791	0.4030		0	-2	3.1	-72.06
c.3659A>T	E1220V 2D AIThe SynGAP1 missense variant E1220V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that E1220V is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-15.193	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.444	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.0552	0.4452		-2	-2	7.7	-29.98
c.3660G>C	E1220D 2D AIThe missense change E1220D occurs in the coiled‑coil domain of SynGAP1. ClinVar contains no entry for this variant and it is absent from gnomAD. Functional prediction tools cluster into two groups: a single benign call from REVEL, and a consensus of pathogenic predictions from the remaining methods (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus likewise indicates pathogenic. Foldetta stability analysis is not available for this variant. Taken together, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with the absence of a ClinVar classification. The variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-8.820	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.178	Likely Benign	-2.59	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.1597	0.2810		3	2	0.0	-14.03
c.3660G>T	E1220D 2D AIThe SynGAP1 missense variant E1220D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from 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	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-8.820	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.179	Likely Benign	-2.59	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.1597	0.2810		3	2	0.0	-14.03
c.3661C>T	R1221W 2D AIThe SynGAP1 missense variant R1221W is listed in ClinVar with an uncertain significance (ClinVar ID 1050818.0) and is present in the gnomAD database (gnomAD ID 6‑33446653‑C‑T). Functional prediction tools show a split assessment: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy analyses further refine the picture: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—deems it likely pathogenic. No Foldetta stability assessment is available for this residue. Overall, the majority of computational evidence points toward a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a definitive benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375					Conflicting		3	6-33446653-C-T	1	6.20e-7	-10.938	Likely Pathogenic	0.651	Likely Pathogenic	Likely Benign										0.174	Likely Benign	-4.57	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	2.50	Benign	0.01	Affected	3.77	5	0.1242	0.2585		2	-3	3.6	30.03
c.3662G>C	R1221P 2D AIThe SynGAP1 missense variant R1221P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote from 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 from multiple prediction algorithms and the high‑accuracy tools points to a pathogenic effect for R1221P. 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	Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375											-14.148	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-3.50	Deleterious	0.999	Probably Damaging	0.968	Probably Damaging	2.52	Benign	0.05	Affected			0.2002	0.3095		0	-2	2.9	-59.07
c.3664A>G	R1222G 2D AIThe SynGAP1 missense change R1222G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools split into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, 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, 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 evidence points to a pathogenic impact, 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	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.498	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.226	Likely Benign	-5.41	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.10	Tolerated			0.3012	0.2305		-3	-2	4.1	-99.14
c.3664A>T	R1222W 2D AIThe SynGAP1 missense variant R1222W is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized yields an Uncertain result and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1222W. This conclusion is not contradicted by ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.933	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.260	Likely Benign	-6.00	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.03	Affected			0.0964	0.2761		2	-3	3.6	30.03
c.3665G>A	R1222K 2D AIThe SynGAP1 missense variant R1222K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized classifies the change as benign, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus designation but contradicts the benign calls from several other predictors. Thus, based on the current computational predictions, the variant is most likely pathogenic, and this assessment aligns with the lack of ClinVar reporting rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-9.148	Likely Pathogenic	0.689	Likely Pathogenic	Likely Benign										0.249	Likely Benign	-2.05	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.57	Pathogenic	0.54	Tolerated			0.3714	0.2611		3	2	0.6	-28.01
c.3665G>C	R1222T 2D AIThe SynGAP1 missense variant R1222T is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R1222T is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.164	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.407	Likely Benign	-4.39	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.13	Tolerated			0.1550	0.2851		-1	-1	3.8	-55.08
c.3665G>T	R1222M 2D AIThe SynGAP1 missense variant R1222M 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 SIFT, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is “Likely Pathogenic,” and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-12.190	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.398	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.20	Tolerated			0.1069	0.2559		0	-1	6.4	-24.99
c.3666G>C	R1222S 2D AIThe SynGAP1 missense variant R1222S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic impact, 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	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-9.310	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-4.40	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.49	Pathogenic	0.10	Tolerated			0.2951	0.2426		0	-1	3.7	-69.11
c.3666G>T	R1222S 2D AIThe SynGAP1 missense variant R1222S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and SIFT, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy prediction tools 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	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-9.310	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.280	Likely Benign	-4.40	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.49	Pathogenic	0.10	Tolerated			0.2951	0.2426		0	-1	3.7	-69.11
c.3667C>G	L1223V 2D AIThe SynGAP1 missense variant L1223V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic, reflecting a majority of pathogenic calls. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-8.492	Likely Pathogenic	0.678	Likely Pathogenic	Likely Benign										0.178	Likely Benign	-2.18	Neutral	0.981	Probably Damaging	0.832	Possibly Damaging	1.54	Pathogenic	0.04	Affected			0.1381	0.2988		2	1	0.4	-14.03
c.3668T>A	L1223Q 2D AIThe SynGAP1 missense variant L1223Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-13.700	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous										0.380	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.986	Probably Damaging	1.46	Pathogenic	0.01	Affected			0.1010	0.1119		-2	-2	-7.3	14.97
c.3668T>C	L1223P 2D AIThe SynGAP1 missense variant L1223P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. 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 confirm this: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the concordant pathogenic predictions and the lack of benign 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	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-14.728	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.500	Likely Pathogenic	-5.17	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	1.45	Pathogenic	0.01	Affected			0.3413	0.2352		-3	-3	-5.4	-16.04
c.3668T>G	L1223R 2D AIThe SynGAP1 missense variant L1223R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the 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, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of computational evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-15.396	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.986	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1078	0.0919		-3	-2	-8.3	43.03
c.3671T>C	L1224P 2D AIThe SynGAP1 missense variant L1224P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). In silico predictors that agree on a benign effect include REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also 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 predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500											-11.727	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.149	Likely Benign	-3.18	Deleterious	0.998	Probably Damaging	0.948	Probably Damaging	2.36	Pathogenic	0.07	Tolerated			0.3618	0.1053		-3	-3	-5.4	-16.04
c.3676C>A	Q1226K 2D AIThe SynGAP1 missense variant Q1226K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence therefore points to a likely pathogenic outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta data are missing. Consequently, the variant is most likely pathogenic based on the collective 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	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-13.233	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-3.16	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	1.82	Pathogenic	0.00	Affected			0.1334	0.3199		1	1	-0.4	0.04
c.3676C>G	Q1226E 2D AIThe SynGAP1 missense variant Q1226E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the SGM‑Consensus prediction and does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-11.526	Likely Pathogenic	0.625	Likely Pathogenic	Likely Benign										0.178	Likely Benign	-2.13	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.1005	0.2297		2	2	0.0	0.98
c.3677A>C	Q1226P 2D AIThe SynGAP1 missense variant Q1226P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-13.176	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.418	Likely Benign	-4.72	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.1829	0.4187		0	-1	1.9	-31.01
c.3677A>G	Q1226R 2D AIThe SynGAP1 missense change Q1226R occurs in a coiled‑coil domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, 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	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-12.260	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-3.16	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.1166	0.1234		1	1	-1.0	28.06
c.3677A>T	Q1226L 2D AIThe SynGAP1 missense variant Q1226L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” AlphaMissense‑Optimized is classified as “Uncertain,” and Foldetta’s protein‑folding stability analysis is unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for Q1226L. This conclusion is not contradicted by ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-11.122	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.77	Pathogenic	0.00	Affected			0.0493	0.4282		-2	-2	7.3	-14.97
c.3678G>C	Q1226H 2D AIThe SynGAP1 missense variant Q1226H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists for Q1226H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-8.363	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0913	0.3230		3	0	0.3	9.01
c.3678G>T	Q1226H 2D AIThe SynGAP1 missense variant Q1226H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists for Q1226H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-8.363	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0913	0.3230		3	0	0.3	9.01
c.3679G>A	E1227K 2D AIThe SynGAP1 missense variant E1227K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-11.825	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.280	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.1661	0.6348		0	1	-0.4	-0.94
c.3679G>C	E1227Q 2D AIThe SynGAP1 missense variant E1227Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-9.212	Likely Pathogenic	0.860	Likely Pathogenic	Ambiguous										0.277	Likely Benign	-2.28	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.0761	0.6204		2	2	0.0	-0.98
c.3680A>C	E1227A 2D AIThe SynGAP1 missense variant E1227A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-9.111	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.341	Likely Benign	-4.63	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.3142	0.6025		0	-1	5.3	-58.04
c.3680A>G	E1227G 2D AIThe SynGAP1 missense variant E1227G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (FoldX‑MD/Rosetta stability analysis) is not available for this variant. Overall, the preponderance of evidence from high‑accuracy predictors and consensus methods indicates that E1227G is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-9.328	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.2725	0.5550		0	-2	3.1	-72.06
c.3680A>T	E1227V 2D AIThe SynGAP1 missense variant E1227V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction comes from REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—classify it as pathogenic or 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 preponderance of evidence from multiple independent prediction tools and high‑accuracy methods indicates that E1227V is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-12.852	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.355	Likely Benign	-5.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.0405	0.6559		-2	-2	7.7	-29.98
c.3683A>T	E1228V 2D AIThe SynGAP1 missense variant E1228V is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and the SGM‑Consensus score, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further separate the evidence: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus, derived from a consensus of four high‑confidence predictors, flags the variant as pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this change. Overall, the preponderance of pathogenic predictions, including the SGM‑Consensus, outweighs the benign calls. Therefore, the variant is most likely pathogenic, 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	Coiled-coil	0.517562	Disordered	0.447051	Uncertain	0.892	0.546	0.500											-8.077	Likely Pathogenic	0.440	Ambiguous	Likely Benign										0.293	Likely Benign	-4.55	Deleterious	0.980	Probably Damaging	0.833	Possibly Damaging	2.43	Pathogenic	0.00	Affected			0.0470	0.4252		-2	-2	7.7	-29.98
c.3686A>C	Q1229P 2D AIThe SynGAP1 missense variant Q1229P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is “Likely Pathogenic.” No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375					Uncertain		1				-10.397	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.422	Likely Benign	-3.69	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.75	Pathogenic	0.12	Tolerated	3.77	5	0.2197	0.4107		0	-1	1.9	-31.01
c.3686A>G	Q1229R 2D AIThe SynGAP1 missense variant Q1229R is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL, SIFT, and AlphaMissense‑Optimized, whereas pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments further illustrate this divergence: AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote) indicates pathogenic; Foldetta data are unavailable. With five tools favoring pathogenicity versus two supporting benign, the overall prediction leans toward pathogenic. 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	Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-8.998	Likely Pathogenic	0.518	Ambiguous	Likely Benign										0.282	Likely Benign	-2.53	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.80	Pathogenic	0.16	Tolerated			0.1178	0.1200		1	1	-1.0	28.06
c.3688A>C	T1230P 2D AIThe SynGAP1 missense variant T1230P is not reported in ClinVar and has no entries in gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so no additional stability evidence is provided. Overall, the consensus of available predictions points to a pathogenic effect for T1230P, with no conflict from ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.570702	Disordered	0.486342	Uncertain	0.845	0.543	0.250											-13.200	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.588	Likely Pathogenic	-2.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.54	Benign	0.01	Affected			0.1529	0.3710		0	-1	-0.9	-3.99
c.3692G>T	S1231I 2D AIThe SynGAP1 missense variant S1231I is 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, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains likely pathogenic; Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification for S1231I, and this conclusion does not contradict any existing ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.519419	Binding	0.876	0.544	0.250											-9.360	Likely Pathogenic	0.712	Likely Pathogenic	Likely Benign										0.203	Likely Benign	-3.24	Deleterious	0.966	Probably Damaging	0.690	Possibly Damaging	2.64	Benign	0.04	Affected			0.0701	0.4550		-1	-2	5.3	26.08
c.3694A>G	K1232E 2D AIThe SynGAP1 missense variant K1232E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-10.690	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.2965	0.1039		0	1	0.4	0.94
c.3695A>C	K1232T 2D AIThe SynGAP1 missense variant K1232T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance 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	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-9.276	Likely Pathogenic	0.568	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.1846	0.3196		0	-1	3.2	-27.07
c.3695A>T	K1232I 2D AIThe SynGAP1 K1232I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified 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 points to a pathogenic 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 Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-12.225	Likely Pathogenic	0.896	Likely Pathogenic	Ambiguous										0.197	Likely Benign	-5.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0778	0.3321		-2	-3	8.4	-15.01
c.3696A>C	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, and Foldetta data are not available. Based on the overall evidence, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3696A>T	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3698T>A	I1233N 2D AIThe SynGAP1 I1233N 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 tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic 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	Coiled-coil	0.525368	Disordered	0.564054	Binding	0.881	0.531	0.125											-9.586	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-4.36	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	2.52	Benign	0.00	Affected			0.0879	0.0340		-2	-3	-8.0	0.94
c.3698T>G	I1233S 2D AIThe SynGAP1 missense variant I1233S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and FATHMM, whereas the majority of other predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus likewise indicates likely pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with 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	Coiled-coil	0.525368	Disordered	0.564054	Binding	0.881	0.531	0.125											-8.066	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.184	Likely Benign	-3.60	Deleterious	0.946	Possibly Damaging	0.673	Possibly Damaging	2.53	Benign	0.00	Affected			0.2848	0.0910		-1	-2	-5.3	-26.08
c.3701T>A	L1234Q 2D AIThe SynGAP1 missense variant L1234Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Based on the predominance of pathogenic predictions and the lack of supporting benign evidence, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-12.969	Likely Pathogenic	0.858	Likely Pathogenic	Ambiguous										0.272	Likely Benign	-4.34	Deleterious	0.997	Probably Damaging	0.955	Probably Damaging	1.46	Pathogenic	0.01	Affected			0.0962	0.1049		-2	-2	-7.3	14.97
c.3701T>C	L1234P 2D AIThe SynGAP1 missense variant L1234P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus confirms a Likely Pathogenic status. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-14.931	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-5.19	Deleterious	0.999	Probably Damaging	0.969	Probably Damaging	1.45	Pathogenic	0.01	Affected			0.3201	0.2483		-3	-3	-5.4	-16.04
c.3701T>G	L1234R 2D AIThe SynGAP1 missense change L1234R occurs in a coiled‑coil domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-15.015	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.211	Likely Benign	-4.52	Deleterious	0.997	Probably Damaging	0.939	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1061	0.0849		-3	-2	-8.3	43.03
c.3707A>C	Q1236P 2D AIThe SynGAP1 missense variant Q1236P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-10.868	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.417	Likely Benign	-3.16	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.65	Benign	0.01	Affected			0.1768	0.3847		0	-1	1.9	-31.01
c.3709T>A	Y1237N 2D AIThe SynGAP1 missense variant Y1237N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-10.505	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.413	Likely Benign	-7.18	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.44	Pathogenic	0.00	Affected			0.2428	0.0173		-2	-2	-2.2	-49.07
c.3709T>C	Y1237H 2D AIThe SynGAP1 missense variant Y1237H 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 only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. ESM1b is uncertain, and Foldetta results are unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. With no conflicting ClinVar evidence, the collective predictions strongly suggest that Y1237H is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-7.985	In-Between	0.995	Likely Pathogenic	Likely Pathogenic										0.383	Likely Benign	-4.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.2221	0.0173		0	2	-1.9	-26.03
c.3709T>G	Y1237D 2D AIThe SynGAP1 missense variant Y1237D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change 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, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so no additional folding‑stability evidence is provided. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-12.849	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.447	Likely Benign	-8.04	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.44	Pathogenic	0.00	Affected			0.4353	0.0173		-4	-3	-2.2	-48.09
c.3710A>C	Y1237S 2D AIThe SynGAP1 missense variant Y1237S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic. The SGM‑Consensus, a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, therefore also predicts pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-10.349	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.463	Likely Benign	-7.21	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.5127	0.0891	Weaken	-3	-2	0.5	-76.10
c.3710A>G	Y1237C 2D AIThe SynGAP1 missense variant Y1237C is listed in gnomAD (variant ID 6‑33446702‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic effect. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized reports a pathogenic outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic.” No Foldetta stability result is available, so it does not influence the overall assessment. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125								6-33446702-A-G	1	6.20e-7	-8.600	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.429	Likely Benign	-7.15	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.43	Pathogenic	0.00	Affected	3.77	5	0.3354	0.1549		-2	0	3.8	-60.04
c.3710A>T	Y1237F 2D AIThe SynGAP1 missense variant Y1237F is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus confirms a likely pathogenic prediction, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for Y1237F. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-4.494	Likely Benign	0.864	Likely Pathogenic	Ambiguous										0.268	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.55	Pathogenic	0.00	Affected			0.1938	0.2424		7	3	4.1	-16.00
c.3713A>C	Q1238P 2D AIThe SynGAP1 missense variant Q1238P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are not available. Based on the collective 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	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-13.929	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.442	Likely Benign	-4.06	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.30	Pathogenic	0.01	Affected			0.1549	0.3619		0	-1	1.9	-31.01
c.3713A>T	Q1238L 2D AIThe SynGAP1 missense variant Q1238L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show the SGM‑Consensus as “Likely Pathogenic,” while AlphaMissense‑Optimized remains uncertain and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-14.299	Likely Pathogenic	0.876	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-4.89	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.31	Pathogenic	0.01	Affected			0.0543	0.3744		-2	-2	7.3	-14.97
c.3714G>C	Q1238H 2D AIThe SynGAP1 missense variant Q1238H is reported in gnomAD (variant ID 6‑33446706‑G‑C) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar classification (none exists). Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250								6-33446706-G-C	1	6.20e-7	-8.647	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.01	Affected	3.77	5	0.1007	0.3004		0	3	0.3	9.01
c.3714G>T	Q1238H 2D AIThe SynGAP1 missense variant Q1238H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all indicate a pathogenic impact. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized classifies the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as Likely Pathogenic. No Foldetta stability prediction is available. Overall, the preponderance of evidence from multiple independent tools points to a pathogenic effect for Q1238H. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-8.647	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.01	Affected	3.77	5	0.1007	0.3004		0	3	0.3	9.01
c.3715G>C	A1239P 2D AIThe SynGAP1 missense variant A1239P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL and polyPhen‑2 HumVar, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that A1239P is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.534779	Binding	0.887	0.542	0.250											-11.055	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.085	Likely Benign	-2.62	Deleterious	0.784	Possibly Damaging	0.390	Benign	2.32	Pathogenic	0.00	Affected			0.1438	0.3450		1	-1	-3.4	26.04
c.3718C>G	R1240G 2D AIThe SynGAP1 missense variant R1240G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the preponderance of evidence indicates that R1240G is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-9.763	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.280	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.3102	0.2895		-3	-2	4.1	-99.14
c.3719G>A	R1240Q 2D AIThe SynGAP1 missense variant R1240Q is reported in gnomAD (variant ID 6-33446711‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. ESM1b is uncertain. The high‑accuracy consensus (SGM‑Consensus) – a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN – is classified as Likely Pathogenic. AlphaMissense‑Optimized remains benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of predictions (six pathogenic vs. two benign) indicates that 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	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375								6-33446711-G-A	2	1.24e-6	-7.110	In-Between	0.717	Likely Pathogenic	Likely Benign										0.304	Likely Benign	-3.09	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.69	Pathogenic	0.00	Affected	3.77	5	0.2377	0.1992		1	1	1.0	-28.06
c.3719G>C	R1240P 2D AIThe SynGAP1 missense variant R1240P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-16.120	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.473	Likely Benign	-5.45	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.2037	0.3768		0	-2	2.9	-59.07
c.3719G>T	R1240L 2D AIThe SynGAP1 missense variant R1240L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, R1240L is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-10.181	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic										0.372	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.1513	0.3394		-3	-2	8.3	-43.03
c.3721C>G	L1241V 2D AIThe SynGAP1 missense variant L1241V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (the combined FoldX‑MD and Rosetta stability assessment) is not available for this variant. Overall, the preponderance of evidence from high‑accuracy predictors points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-8.771	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous										0.153	Likely Benign	-2.33	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.70	Pathogenic	0.00	Affected			0.1596	0.1883		2	1	0.4	-14.03
c.3722T>A	L1241Q 2D AIThe SynGAP1 missense variant L1241Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-10.429	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.386	Likely Benign	-4.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.1217	0.0488		-2	-2	-7.3	14.97
c.3722T>C	L1241P 2D AIThe SynGAP1 missense variant L1241P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-16.301	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.471	Likely Benign	-5.42	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.3640	0.1048		-3	-3	-5.4	-16.04
c.3722T>G	L1241R 2D AIThe SynGAP1 missense variant L1241R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-14.178	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.1204	0.0488		-3	-2	-8.3	43.03
c.3724G>A	E1242K 2D AIThe SynGAP1 missense variant E1242K is catalogued in gnomAD (6‑33446716‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicting REVEL score contrasts with a pathogenic consensus from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic,” and the protein‑folding stability method Foldetta is not available for this variant. Taken together, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.557691	Disordered	0.456349	Uncertain	0.870	0.549	0.500								6-33446716-G-A	1	6.20e-7	-10.075	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous										0.179	Likely Benign	-3.13	Deleterious	0.939	Possibly Damaging	0.670	Possibly Damaging	2.22	Pathogenic	0.00	Affected	3.77	5	0.1520	0.4024		1	0	-0.4	-0.94
c.3725A>T	E1242V 2D AIThe E1242V missense change occurs in the coiled‑coil domain of SynGAP1. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized. Those that predict a pathogenic outcome include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (which is “Likely Pathogenic”). ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which simply lacks an entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.557691	Disordered	0.456349	Uncertain	0.870	0.549	0.500											-7.456	In-Between	0.691	Likely Pathogenic	Likely Benign										0.267	Likely Benign	-5.46	Deleterious	0.991	Probably Damaging	0.898	Possibly Damaging	2.17	Pathogenic	0.00	Affected			0.0447	0.4320		-2	-2	7.7	-29.98
c.3730A>C	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3730A>T	S1244C 2D AIThe SynGAP1 missense variant S1244C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus (majority vote) predicts 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 indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-9.792	Likely Pathogenic	0.625	Likely Pathogenic	Likely Benign										0.270	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.07	Pathogenic	0.04	Affected			0.0875	0.4616		0	-1	3.3	16.06
c.3731G>A	S1244N 2D AIThe SynGAP1 missense variant S1244N is listed in ClinVar with an “Uncertain” status (ClinVar ID 931075.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas PolyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a pathogenic effect, which does not contradict the ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500					Uncertain		1				-9.008	Likely Pathogenic	0.751	Likely Pathogenic	Likely Benign										0.154	Likely Benign	-1.87	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.10	Pathogenic	0.15	Tolerated	3.77	5	0.1033	0.3464		1	1	-2.7	27.03
c.3731G>T	S1244I 2D AIThe SynGAP1 missense variant S1244I is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, 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	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-13.073	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.284	Likely Benign	-4.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.08	Pathogenic	0.02	Affected			0.0780	0.4684		-1	-2	5.3	26.08
c.3732T>A	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3732T>G	S1244R 2D AIThe SynGAP1 missense variant S1244R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-10.986	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.274	Likely Benign	-3.49	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.09	Pathogenic	0.04	Affected			0.0778	0.3098		0	-1	-3.7	69.11
c.3733G>A	E1245K 2D AIThe SynGAP1 missense variant E1245K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that E1245K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.911	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.276	Likely Benign	-3.22	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1627	0.6574		0	1	-0.4	-0.94
c.3733G>C	E1245Q 2D AIThe SynGAP1 missense change E1245Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3 pathogenic vs. 1 benign). High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is not available. Consequently, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.323	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous										0.210	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.0819	0.5952		2	2	0.0	-0.98
c.3734A>C	E1245A 2D AIThe SynGAP1 missense variant E1245A is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL is the sole tool that predicts a benign effect, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise indicates a likely pathogenic effect. Foldetta results are not available for this variant. Overall, the consensus of the available predictions indicates that E1245A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.433	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic										0.311	Likely Benign	-4.85	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.2555	0.5721		0	-1	5.3	-58.04
c.3734A>G	E1245G 2D AIThe SynGAP1 missense variant E1245G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified 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 points to a pathogenic 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 Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-12.113	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.299	Likely Benign	-5.65	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.2145	0.5447		0	-2	3.1	-72.06
c.3734A>T	E1245V 2D AIThe SynGAP1 missense change E1245V is not reported in ClinVar and is absent from gnomAD. Prediction tools that flag the variant as benign include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise reports a likely pathogenic outcome. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect for E1245V, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-12.988	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-5.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.21	Pathogenic	0.00	Affected			0.0518	0.6856		-2	-2	7.7	-29.98
c.3739A>G	R1247G 2D AIThe SynGAP1 missense variant R1247G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain and SGM‑Consensus is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence favors 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	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-7.920	In-Between	0.724	Likely Pathogenic	Likely Benign										0.195	Likely Benign	-5.58	Deleterious	0.980	Probably Damaging	0.721	Possibly Damaging	1.70	Pathogenic	0.00	Affected			0.3047	0.2327		-3	-2	4.1	-99.14
c.3739A>T	R1247W 2D AIThe SynGAP1 missense variant R1247W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome. No Foldetta stability result is available. Overall, the balance of evidence points to a pathogenic classification for R1247W, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-9.694	Likely Pathogenic	0.676	Likely Pathogenic	Likely Benign										0.159	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.982	Probably Damaging	1.68	Pathogenic	0.00	Affected			0.0963	0.2524		2	-3	3.6	30.03
c.3740G>C	R1247T 2D AIThe SynGAP1 missense variant R1247T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. No Foldetta stability result is available. Overall, the majority of evidence points to a pathogenic impact, and this conclusion 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	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.302	Likely Benign	0.598	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-4.79	Deleterious	0.980	Probably Damaging	0.783	Possibly Damaging	1.71	Pathogenic	0.00	Affected			0.1543	0.2403		-1	-1	3.8	-55.08
c.3740G>T	R1247M 2D AIThe SynGAP1 missense variant R1247M is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta data are unavailable. Overall, the majority of evidence points to a pathogenic impact, 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	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.347	Likely Benign	0.589	Likely Pathogenic	Likely Benign										0.239	Likely Benign	-4.79	Deleterious	1.000	Probably Damaging	0.961	Probably Damaging	1.68	Pathogenic	0.00	Affected			0.1039	0.2122		0	-1	6.4	-24.99
c.3741G>C	R1247S 2D AIThe SynGAP1 missense variant R1247S 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1247S. 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	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.935	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-4.79	Deleterious	0.961	Probably Damaging	0.721	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2802	0.1977		0	-1	3.7	-69.11
c.3741G>T	R1247S 2D AIThe SynGAP1 missense variant R1247S 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1247S. 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	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.935	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-4.79	Deleterious	0.961	Probably Damaging	0.721	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2802	0.1977		0	-1	3.7	-69.11
c.3743T>A	L1248Q 2D AIThe SynGAP1 missense variant L1248Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) confirms this prediction; the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect for this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-6.471	Likely Benign	0.981	Likely Pathogenic	Likely Pathogenic										0.364	Likely Benign	-4.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.1067	0.0688		-2	-2	-7.3	14.97
c.3743T>C	L1248P 2D AIThe SynGAP1 missense variant L1248P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-14.647	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.410	Likely Benign	-5.45	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.3596	0.0848		-3	-3	-5.4	-16.04
c.3743T>G	L1248R 2D AIThe SynGAP1 missense variant L1248R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-11.285	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.370	Likely Benign	-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.1222	0.0488		-3	-2	-8.3	43.03
c.3745A>G	R1249G 2D AIThe SynGAP1 missense variant R1249G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain and SGM‑Consensus is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence favors 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	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-7.405	In-Between	0.684	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-5.38	Deleterious	0.990	Probably Damaging	0.828	Possibly Damaging	1.70	Pathogenic	0.00	Affected			0.3087	0.2393		-3	-2	4.1	-99.14
c.3745A>T	R1249W 2D AIThe SynGAP1 missense variant R1249W is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) is pathogenic, and no Foldetta stability data are available. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus designation and contradicts the benign predictions from a minority of tools. Thus, the variant is most likely pathogenic, and this conclusion aligns with the lack of ClinVar annotation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-9.841	Likely Pathogenic	0.477	Ambiguous	Likely Benign										0.209	Likely Benign	-6.18	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	1.68	Pathogenic	0.00	Affected			0.1256	0.2179		2	-3	3.6	30.03
c.3746G>C	R1249T 2D AIThe SynGAP1 missense variant R1249T is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The SGM‑Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence (10 pathogenic vs. 2 benign predictions) points to a pathogenic impact for R1249T. 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	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-8.014	Likely Pathogenic	0.712	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-4.59	Deleterious	0.990	Probably Damaging	0.903	Possibly Damaging	1.71	Pathogenic	0.00	Affected			0.1646	0.2458		-1	-1	3.8	-55.08
c.3746G>T	R1249M 2D AIThe SynGAP1 missense variant R1249M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in‑silico tools indicates that R1249M is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-8.520	Likely Pathogenic	0.643	Likely Pathogenic	Likely Benign										0.232	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.979	Probably Damaging	1.68	Pathogenic	0.00	Affected			0.1318	0.2173		0	-1	6.4	-24.99
c.3747G>C	R1249S 2D AIThe SynGAP1 missense variant R1249S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and labels the variant as Likely Pathogenic. High‑accuracy assessments are limited: AlphaMissense‑Optimized returns an Uncertain result, and the Foldetta stability analysis is not available for this residue. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because no ClinVar entry exists for R1249S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-6.936	Likely Benign	0.828	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.52	Deleterious	0.980	Probably Damaging	0.828	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2777	0.1843		0	-1	3.7	-69.11
c.3747G>T	R1249S 2D AIThe SynGAP1 missense variant R1249S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and labels the variant as Likely Pathogenic. High‑accuracy assessments are limited: AlphaMissense‑Optimized returns an Uncertain result, and the Foldetta stability analysis is not available for this residue. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because no ClinVar entry exists for R1249S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-6.936	Likely Benign	0.828	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.52	Deleterious	0.980	Probably Damaging	0.828	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2777	0.1843		0	-1	3.7	-69.11
c.3749A>C	Q1250P 2D AIThe SynGAP1 missense variant Q1250P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. No Foldetta stability prediction is available for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-10.383	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.085	Likely Benign	-3.12	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.62	Benign	0.02	Affected			0.2376	0.4149		0	-1	1.9	-31.01
c.3751C>A	Q1251K 2D AIThe SynGAP1 missense variant Q1251K is catalogued in gnomAD (ID 6‑33446743‑C‑A) but has no ClinVar entry. Functional prediction tools show a split: benign calls from REVEL and FATHMM, whereas the majority—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as Uncertain, SGM‑Consensus remains Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875								6-33446743-C-A	1	6.20e-7	-11.113	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous										0.208	Likely Benign	-2.92	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.53	Benign	0.00	Affected	3.77	5	0.1418	0.2635		1	1	-0.4	0.04
c.3752A>C	Q1251P 2D AIThe SynGAP1 missense variant Q1251P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance 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	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-14.584	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.344	Likely Benign	-4.45	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.43	Pathogenic	0.00	Affected			0.2418	0.4408		0	-1	1.9	-31.01
c.3752A>G	Q1251R 2D AIThe SynGAP1 missense variant Q1251R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The 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 Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-9.456	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.236	Likely Benign	-2.92	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.50	Benign	0.00	Affected			0.1257	0.1224		1	1	-1.0	28.06
c.3753G>C	Q1251H 2D AIThe SynGAP1 missense variant Q1251H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while REVEL predicts a benign outcome. Two tools return uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a harmful interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains inconclusive. No Foldetta stability data are available. Overall, the balance of evidence points to a pathogenic effect for Q1251H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.561	In-Between	0.937	Likely Pathogenic	Ambiguous										0.176	Likely Benign	-3.71	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1132	0.2399		3	0	0.3	9.01
c.3753G>T	Q1251H 2D AIThe SynGAP1 missense variant Q1251H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while REVEL predicts a benign outcome. Two tools return uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a harmful interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains inconclusive. No Foldetta stability data are available. Overall, the balance of evidence points to a pathogenic effect for Q1251H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.561	In-Between	0.937	Likely Pathogenic	Ambiguous										0.176	Likely Benign	-3.71	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1132	0.2399		3	0	0.3	9.01
c.3754C>A	Q1252K 2D AIThe SynGAP1 missense variant Q1252K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the predominance of pathogenic predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-13.590	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous										0.217	Likely Benign	-3.22	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1460	0.2518		1	1	-0.4	0.04
c.3755A>C	Q1252P 2D AIThe SynGAP1 missense variant Q1252P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance 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	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-14.386	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.352	Likely Benign	-4.75	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1998	0.3742		0	-1	1.9	-31.01
c.3755A>G	Q1252R 2D AIThe SynGAP1 missense variant Q1252R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) support a pathogenic effect, while only one tool (REVEL) indicates benign. High‑accuracy assessments further support a deleterious impact: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, and there is no contradiction with ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-11.890	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-3.26	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1284	0.0854		1	1	-1.0	28.06
c.3755A>T	Q1252L 2D AIThe SynGAP1 missense variant Q1252L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-8.110	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous										0.295	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0593	0.3689		-2	-2	7.3	-14.97
c.3756G>C	Q1252H 2D AIThe SynGAP1 missense variant Q1252H is 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as deleterious. 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 Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance 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	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-6.891	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-4.02	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1038	0.2149		3	0	0.3	9.01
c.3756G>T	Q1252H 2D AIThe SynGAP1 missense variant Q1252H is 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in‑silico predictors 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.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-6.891	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-4.02	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1038	0.2149		3	0	0.3	9.01
c.3760G>A	E1254K 2D AIThe SynGAP1 missense variant E1254K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1254K. This prediction is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-11.288	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-2.97	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.36	Pathogenic	0.02	Affected			0.1653	0.5488		0	1	-0.4	-0.94
c.3761A>C	E1254A 2D AIThe SynGAP1 missense variant E1254A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining ten tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools 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	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-8.943	Likely Pathogenic	0.658	Likely Pathogenic	Likely Benign										0.270	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.35	Pathogenic	0.02	Affected			0.3029	0.5547		0	-1	5.3	-58.04
c.3761A>G	E1254G 2D AIThe SynGAP1 missense variant E1254G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized indicates a benign change, but the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the SGM Consensus suggests that the variant is most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-10.156	Likely Pathogenic	0.706	Likely Pathogenic	Likely Benign										0.315	Likely Benign	-4.52	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.34	Pathogenic	0.01	Affected			0.2636	0.5072		0	-2	3.1	-72.06
c.3761A>T	E1254V 2D AIThe SynGAP1 missense variant E1254V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by the majority of in silico methods. High‑accuracy assessments further reinforce a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-9.913	Likely Pathogenic	0.814	Likely Pathogenic	Ambiguous										0.350	Likely Benign	-5.15	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.0481	0.5894		-2	-2	7.7	-29.98
c.3763A>C	K1255Q 2D AIThe SynGAP1 missense variant K1255Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for K1255Q, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.680	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.87	Pathogenic	0.00	Affected			0.3625	0.1102		1	1	0.4	-0.04
c.3763A>G	K1255E 2D AIThe SynGAP1 missense variant K1255E is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-15.072	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.308	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.88	Pathogenic	0.00	Affected			0.3094	0.0877		0	1	0.4	0.94
c.3764A>C	K1255T 2D AIThe SynGAP1 missense variant K1255T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as pathogenic; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-9.745	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.360	Likely Benign	-4.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.1755	0.2628		0	-1	3.2	-27.07
c.3764A>G	K1255R 2D AIThe SynGAP1 K1255R 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 PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the change as damaging. The high‑accuracy consensus approach (SGM‑Consensus) – a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN – yields a pathogenic verdict (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for K1255R. This prediction is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-9.687	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous										0.171	Likely Benign	-2.43	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.3727	0.0878		3	2	-0.6	28.01
c.3764A>T	K1255M 2D AIThe SynGAP1 missense variant K1255M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-10.554	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.393	Likely Benign	-4.82	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.82	Pathogenic	0.00	Affected			0.0776	0.3154		0	-1	5.8	3.02
c.3765G>C	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3765G>T	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3766G>A	D1256N 2D AIThe SynGAP1 D1256N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-10.375	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.0832	0.4219		2	1	0.0	-0.98
c.3766G>C	D1256H 2D AIThe SynGAP1 missense variant D1256H is predicted to be pathogenic by every available in‑silico tool. Benign predictions are absent; all listed predictors—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as damaging. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta results are not available. ClinVar contains no entry for this variant, and it is absent from gnomAD, so there is no existing clinical annotation to contradict the computational predictions. Overall, the evidence strongly suggests the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-14.272	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.508	Likely Pathogenic	-5.29	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.0963	0.4798		1	-1	0.3	22.05
c.3766G>T	D1256Y 2D AIThe SynGAP1 missense variant D1256Y is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a deleterious effect. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that D1256Y is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-15.855	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.507	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.0446	0.4275		-4	-3	2.2	48.09
c.3767A>C	D1256A 2D AIThe SynGAP1 D1256A missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. 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 pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta results are not available. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-11.665	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.443	Likely Benign	-6.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.2830	0.4451		0	-2	5.3	-44.01
c.3767A>G	D1256G 2D AIThe SynGAP1 missense variant D1256G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the benign‑predicting REVEL score, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenicity. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect for D1256G. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-11.341	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.457	Likely Benign	-5.45	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.00	Affected			0.2886	0.5040		1	-1	3.1	-58.04
c.3767A>T	D1256V 2D AIThe SynGAP1 missense variant D1256V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact largely agree on a deleterious effect: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the only benign prediction comes from REVEL. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Pathogenic.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-14.067	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic										0.446	Likely Benign	-6.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.0573	0.4407		-2	-3	7.7	-15.96
c.3768T>A	D1256E 2D AIThe SynGAP1 D1256E 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 and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, which is a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Taken together, the consensus of most evidence points to a pathogenic effect, and this conclusion does not contradict any existing ClinVar annotation (none is present). Thus, the variant is most likely pathogenic based on current predictive tools. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-5.806	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.149	Likely Benign	-2.71	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.72	Pathogenic	0.00	Affected			0.1022	0.4172		3	2	0.0	14.03
c.3768T>G	D1256E 2D AIThe SynGAP1 D1256E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and therefore reports the variant as likely pathogenic. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Taken together, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. 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	Coiled-coil	0.549308	Disordered	0.445789	Uncertain	0.876	0.571	0.625											-5.806	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.149	Likely Benign	-2.71	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.72	Pathogenic	0.00	Affected			0.1022	0.4172		3	2	0.0	14.03
c.3769T>C	S1257P 2D AIThe SynGAP1 missense variant S1257P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic impact 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 and the SGM‑Consensus as likely pathogenic; Foldetta results are unavailable. Overall, the majority of computational 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	Coiled-coil	0.541878	Disordered	0.482380	Uncertain	0.889	0.572	0.375											-11.985	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.150	Likely Benign	-2.54	Deleterious	0.966	Probably Damaging	0.773	Possibly Damaging	2.55	Benign	0.06	Tolerated			0.1656	0.4519		1	-1	-0.8	10.04
c.3772C>A	Q1258K 2D AIThe SynGAP1 missense variant Q1258K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify it as pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by seven distinct algorithms. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as likely pathogenic, and Foldetta data are not available. Taken together, the preponderance of evidence from multiple pathogenic predictors and the SGM‑Consensus suggests that the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.927	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.227	Likely Benign	-3.19	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1151	0.2761		1	1	-0.4	0.04
c.3772C>G	Q1258E 2D AIThe SynGAP1 missense variant Q1258E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-9.894	Likely Pathogenic	0.666	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-2.39	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.01	Pathogenic	0.00	Affected			0.0958	0.1897		2	2	0.0	0.98
c.3773A>C	Q1258P 2D AIThe SynGAP1 missense variant Q1258P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-16.904	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.440	Likely Benign	-4.79	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1727	0.4187		0	-1	1.9	-31.01
c.3773A>G	Q1258R 2D AIThe SynGAP1 missense variant Q1258R is listed in ClinVar with an uncertain significance (ClinVar ID 3359527.0) and is not observed in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while only REVEL predicts a benign outcome. The high‑accuracy predictors give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available output for this variant. Based on the preponderance of pathogenic predictions and the SGM Consensus, the variant is most likely pathogenic, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250					Uncertain		1				-10.971	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.316	Likely Benign	-3.19	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1027	0.0991		1	1	-1.0	28.06
c.3773A>T	Q1258L 2D AIThe SynGAP1 missense variant Q1258L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) predict pathogenic, while only one tool (REVEL) predicts benign. High‑accuracy assessments further support a deleterious effect: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, indicating no conflicting evidence from population databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.302	Likely Pathogenic	0.895	Likely Pathogenic	Ambiguous										0.341	Likely Benign	-5.55	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0448	0.4137		-2	-2	7.3	-14.97
c.3774G>C	Q1258H 2D AIThe SynGAP1 missense variant Q1258H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also leans pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-5.465	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-3.99	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.0735	0.3066		3	0	0.3	9.01
c.3774G>T	Q1258H 2D AIThe SynGAP1 missense variant Q1258H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-5.465	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-3.99	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.0735	0.3066		3	0	0.3	9.01
c.3776T>A	I1259N 2D AIThe SynGAP1 missense variant I1259N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also reports a likely pathogenic classification. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for I1259N. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.979	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.459	Likely Benign	-3.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.51	Benign	0.00	Affected			0.0799	0.0340		-2	-3	-8.0	0.94
c.3776T>G	I1259S 2D AIThe SynGAP1 missense variant I1259S is 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 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 further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled “Likely Pathogenic.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that 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	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-12.269	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.53	Benign	0.01	Affected			0.3004	0.1110		-1	-2	-5.3	-26.08
c.3778A>G	K1260E 2D AIThe SynGAP1 missense variant K1260E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions point to a pathogenic effect, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.913	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous										0.462	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.3129	0.0877		0	1	0.4	0.94
c.3779A>C	K1260T 2D AIThe SynGAP1 missense variant K1260T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in‑silico tools indicates that K1260T is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.099	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign										0.387	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1859	0.3028		0	-1	3.2	-27.07
c.3779A>T	K1260M 2D AIThe SynGAP1 missense variant K1260M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the substitution as pathogenic. High‑accuracy assessments further support a deleterious impact: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports “Likely Pathogenic”; AlphaMissense‑Optimized yields an uncertain result, and Foldetta’s stability prediction is unavailable. Taken together, the evidence overwhelmingly points to a pathogenic effect for K1260M. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.938	Likely Pathogenic	0.887	Likely Pathogenic	Ambiguous										0.400	Likely Benign	-4.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.0746	0.3366		0	-1	5.8	3.02
c.3780G>C	K1260N 2D AIThe SynGAP1 missense variant K1260N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, 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	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3780G>T	K1260N 2D AIThe SynGAP1 missense variant K1260N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, 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	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3781A>C	S1261R 2D AIThe SynGAP1 missense variant S1261R 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 ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for S1261R, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-4.363	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.152	Likely Benign	-2.97	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.04	Affected			0.0661	0.2642		0	-1	-3.7	69.11
c.3781A>T	S1261C 2D AIThe SynGAP1 missense variant S1261C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the variant as damaging. The SGM‑Consensus, which aggregates these predictions, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized remains benign, but the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-8.275	Likely Pathogenic	0.322	Likely Benign	Likely Benign										0.113	Likely Benign	-3.51	Deleterious	0.999	Probably Damaging	0.947	Probably Damaging	2.20	Pathogenic	0.04	Affected			0.0760	0.4580		0	-1	3.3	16.06
c.3782G>T	S1261I 2D AIThe SynGAP1 missense variant S1261I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score indicates a benign effect, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. No Foldetta stability assessment is available for this residue. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic impact for S1261I. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-8.835	Likely Pathogenic	0.761	Likely Pathogenic	Likely Benign										0.244	Likely Benign	-4.20	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.02	Affected			0.0631	0.4410		-1	-2	5.3	26.08
c.3783C>A	S1261R 2D AIThe SynGAP1 missense variant S1261R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic classification, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-4.363	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.97	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.04	Affected			0.0661	0.2642		0	-1	-3.7	69.11
c.3783C>G	S1261R 2D AIThe SynGAP1 missense variant S1261R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that S1261R is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-4.363	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.97	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.04	Affected			0.0661	0.2642		0	-1	-3.7	69.11
c.3784A>T	I1262F 2D AIThe SynGAP1 missense variant I1262F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-11.343	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.515	Likely Pathogenic	-3.32	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0532	0.2731		1	0	-1.7	34.02
c.3785T>A	I1262N 2D AIThe SynGAP1 missense variant I1262N is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that I1262N is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-14.512	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.463	Likely Benign	-5.81	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.0940	0.0340		-2	-3	-8.0	0.94
c.3785T>C	I1262T 2D AIThe SynGAP1 missense variant I1262T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic status. The Foldetta stability analysis is not available for this variant. Overall, the consensus of all available predictions points to a pathogenic effect, and 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	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-11.985	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.514	Likely Pathogenic	-4.14	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.1109	0.1419		0	-1	-5.2	-12.05
c.3785T>G	I1262S 2D AIThe SynGAP1 missense variant I1262S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for I1262S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-15.167	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.483	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.2943	0.1110		-1	-2	-5.3	-26.08
c.3786C>G	I1262M 2D AIThe SynGAP1 missense variant I1262M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also leans pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This conclusion 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	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-9.081	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.248	Likely Benign	-2.49	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0671	0.2726		2	1	-2.6	18.03
c.3787A>T	I1263F 2D AIThe SynGAP1 missense variant I1263F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Because the majority of evidence points to a deleterious effect 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	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-5.887	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.335	Likely Benign	-3.32	Deleterious	0.968	Probably Damaging	0.637	Possibly Damaging	1.81	Pathogenic	0.00	Affected			0.0494	0.2375		1	0	-1.7	34.02
c.3788T>A	I1263N 2D AIThe SynGAP1 missense variant I1263N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-9.158	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.379	Likely Benign	-5.80	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	1.79	Pathogenic	0.00	Affected			0.1041	0.0340		-2	-3	-8.0	0.94
c.3788T>C	I1263T 2D AIThe SynGAP1 missense variant I1263T is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33446780‑T‑C). Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report pathogenicity, while only ESM1b predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a pathogenic effect, which aligns with the ClinVar designation of uncertainty but does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000					Uncertain		1	6-33446780-T-C	2	1.24e-6	-6.564	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.529	Likely Pathogenic	-4.15	Deleterious	0.946	Possibly Damaging	0.673	Possibly Damaging	1.81	Pathogenic	0.00	Affected	3.77	5	0.1221	0.1051		0	-1	-5.2	-12.05
c.3788T>G	I1263S 2D AIThe SynGAP1 missense variant I1263S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled 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 indicates that 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	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-8.074	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.493	Likely Benign	-4.97	Deleterious	0.984	Probably Damaging	0.825	Possibly Damaging	1.80	Pathogenic	0.00	Affected			0.3242	0.0910		-1	-2	-5.3	-26.08
c.3793A>G	R1265G 2D AIThe SynGAP1 missense variant R1265G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all label the change as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, while a Foldetta stability analysis is unavailable. Based on the unanimous pathogenic predictions and the lack of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-12.732	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.523	Likely Pathogenic	-5.80	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.3520	0.3759		-3	-2	4.1	-99.14
c.3793A>T	R1265W 2D AIThe SynGAP1 missense variant R1265W is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool in the dataset predicts a benign outcome, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates a pathogenic change, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta results are not available, so they do not influence the conclusion. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-14.584	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.505	Likely Pathogenic	-6.54	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.1166	0.3868		2	-3	3.6	30.03
c.3794G>C	R1265T 2D AIThe SynGAP1 missense variant R1265T is reported in ClinVar as Pathogenic (ClinVar ID 522047.0) and is not found in gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions supports a pathogenic classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000					Likely Pathogenic		1				-10.129	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.529	Likely Pathogenic	-4.97	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.29	Pathogenic	0.00	Affected	3.77	5	0.1947	0.4618		-1	-1	3.8	-55.08
c.3794G>T	R1265M 2D AIThe SynGAP1 missense variant R1265M is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that R1265M is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-13.657	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.495	Likely Benign	-4.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.1442	0.4082		0	-1	6.4	-24.99
c.3795G>C	R1265S 2D AIThe SynGAP1 missense variant R1265S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-9.874	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.289	Likely Benign	-4.96	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.40	Pathogenic	0.00	Affected			0.3525	0.3993		0	-1	3.7	-69.11
c.3795G>T	R1265S 2D AIThe SynGAP1 missense variant R1265S is not reported in ClinVar and has no entry in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance 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	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-9.874	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.289	Likely Benign	-4.96	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.40	Pathogenic	0.00	Affected			0.3525	0.3993		0	-1	3.7	-69.11
c.3796C>A	L1266M 2D AIThe SynGAP1 missense variant L1266M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a larger set—polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an uncertain result, SGM‑Consensus remains likely pathogenic, and Foldetta data are unavailable. Overall, the majority of evidence points toward a pathogenic effect for L1266M. This conclusion does not conflict with 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	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-8.257	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-1.67	Neutral	0.999	Probably Damaging	0.989	Probably Damaging	2.12	Pathogenic	0.00	Affected			0.0627	0.3113		4	2	-1.9	18.03
c.3796C>G	L1266V 2D AIThe SynGAP1 missense variant L1266V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-10.024	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.53	Deleterious	0.995	Probably Damaging	0.890	Possibly Damaging	2.16	Pathogenic	0.00	Affected			0.1301	0.3118		2	1	0.4	-14.03
c.3797T>A	L1266Q 2D AIThe SynGAP1 missense variant L1266Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—classify the variant as pathogenic or 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 preponderance of evidence points to a pathogenic effect for L1266Q, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-16.101	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.374	Likely Benign	-5.02	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.12	Pathogenic	0.00	Affected			0.0906	0.1249		-2	-2	-7.3	14.97
c.3797T>C	L1266P 2D AIThe SynGAP1 missense variant L1266P is reported in gnomAD (6‑33447845‑T‑C) but has no ClinVar entry. Prediction tools cluster into two groups: benign predictions are made only by REVEL, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic.” The Foldetta stability analysis is unavailable for this variant. Overall, the consensus of both general and high‑accuracy predictors points to a pathogenic impact, 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	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000								6-33447845-T-C			-16.566	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.424	Likely Benign	-5.83	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.10	Pathogenic	0.00	Affected	3.77	5	0.3150	0.2283		-3	-3	-5.4	-16.04
c.3797T>G	L1266R 2D AISynGAP1 missense variant L1266R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta results are unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools points to a pathogenic effect, with no conflict from ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-16.676	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.391	Likely Benign	-5.04	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1063	0.0891		-3	-2	-8.3	43.03
c.3800T>A	M1267K 2D AIThe SynGAP1 missense variant M1267K is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a pathogenic outcome (3/4 pathogenic). AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Overall, the majority of evidence points to a deleterious effect, classifying the variant as most likely pathogenic. This assessment does not conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-6.415	Likely Benign	0.917	Likely Pathogenic	Ambiguous										0.366	Likely Benign	-5.01	Deleterious	0.884	Possibly Damaging	0.581	Possibly Damaging	2.31	Pathogenic	0.00	Affected			0.1373	0.0488		0	-1	-5.8	-3.02
c.3800T>C	M1267T 2D AIThe SynGAP1 missense variant M1267T is 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) likewise indicates likely pathogenicity. No Foldetta stability prediction is available for this variant. Based on the preponderance of pathogenic predictions, 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	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-5.315	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.270	Likely Benign	-5.00	Deleterious	0.982	Probably Damaging	0.672	Possibly Damaging	2.32	Pathogenic	0.00	Affected			0.2036	0.1934		-1	-1	-2.6	-30.09
c.3800T>G	M1267R 2D AIThe SynGAP1 missense variant M1267R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Grouping by consensus, two tools predict benign and six predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact, 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	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-4.990	Likely Benign	0.899	Likely Pathogenic	Ambiguous										0.366	Likely Benign	-5.03	Deleterious	0.982	Probably Damaging	0.757	Possibly Damaging	2.30	Pathogenic	0.00	Affected			0.1555	0.0837		0	-1	-6.4	24.99
c.3801G>A	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1254	0.2741		2	1	2.6	-18.03
c.3801G>C	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. 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	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1254	0.2741		2	1	2.6	-18.03
c.3801G>T	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. 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	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1254	0.2741		2	1	2.6	-18.03
c.3805G>A	V1269M 2D AIThe SynGAP1 missense variant V1269M is 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is 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 points to a pathogenic effect for V1269M, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.743	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0582	0.3676		2	1	-2.3	32.06
c.3805G>C	V1269L 2D AIThe SynGAP1 missense variant V1269L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate 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. 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 tools 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	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.572	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.299	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0683	0.4082		2	1	-0.4	14.03
c.3805G>T	V1269L 2D AIThe SynGAP1 missense variant V1269L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, 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 preponderance of predictions 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	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.572	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.299	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0683	0.4082		2	1	-0.4	14.03
c.3806T>A	V1269E 2D AIThe SynGAP1 missense change V1269E is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that flag the variant as benign include only REVEL, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classify it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Pathogenic” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar designation of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125					Uncertain		1				-11.418	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.403	Likely Benign	-5.05	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.09	Pathogenic	0.00	Affected	3.77	5	0.0899	0.1557		-2	-2	-7.7	29.98
c.3806T>C	V1269A 2D AIThe SynGAP1 missense variant V1269A is 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 ESM1b, whereas a larger group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and no Foldetta data. Overall, the majority of evidence points to a pathogenic effect. 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	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-6.115	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.38	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.2699	0.2312		0	0	-2.4	-28.05
c.3808G>A	E1270K 2D AIThe SynGAP1 missense variant E1270K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that E1270K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-12.549	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic										0.413	Likely Benign	-3.37	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	2.07	Pathogenic	0.00	Affected			0.1780	0.6276		0	1	-0.4	-0.94
c.3808G>C	E1270Q 2D AIThe SynGAP1 missense variant E1270Q is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include only REVEL, which scores the substitution as benign. In contrast, the majority of in silico predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the change as pathogenic. The high‑accuracy AlphaMissense‑Optimized assessment is uncertain, while the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic outcome. Foldetta predictions are unavailable for this variant. Overall, the preponderance of pathogenic predictions, together with the SGM Consensus result, indicates that E1270Q is most likely pathogenic; this conclusion 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	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-8.645	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-2.53	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.0919	0.5858		2	2	0.0	-0.98
c.3809A>C	E1270A 2D AIThe SynGAP1 missense change E1270A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL is the only score that flags the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM‑Consensus also indicates a likely pathogenic outcome. No Foldetta (FoldX‑MD/Rosetta stability) result is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a pathogenic impact for E1270A, and this conclusion is consistent with the absence of a ClinVar entry (i.e., no contradictory clinical classification). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-12.081	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic										0.388	Likely Benign	-5.04	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.3024	0.5126		0	-1	5.3	-58.04
c.3809A>G	E1270G 2D AIThe SynGAP1 missense variant E1270G is listed in gnomAD (ID 6‑33447857‑A‑G) and has no ClinVar entry. Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic, while Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the absence of a benign consensus, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250								6-33447857-A-G			-12.022	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic										0.385	Likely Benign	-5.90	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.05	Pathogenic	0.00	Affected	3.77	5	0.2415	0.5452		-2	0	3.1	-72.06
c.3809A>T	E1270V 2D AIThe SynGAP1 missense variant E1270V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus agrees. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that E1270V is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-13.293	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.408	Likely Benign	-5.90	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.0570	0.6461		-2	-2	7.7	-29.98
c.3810G>C	E1270D 2D AIThe SynGAP1 missense variant E1270D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective 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	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-9.379	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1655	0.3271		3	2	0.0	-14.03
c.3810G>T	E1270D 2D AIThe SynGAP1 missense variant E1270D is catalogued in gnomAD (6-33447858‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence indicates that E1270D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250								6-33447858-G-T			-9.379	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1655	0.3271		3	2	0.0	-14.03
c.3811G>A	E1271K 2D AIThe SynGAP1 missense variant E1271K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, whereas Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the preponderance of evidence—both from general predictors and the SGM Consensus—leans toward pathogenicity. 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		0.483068	Structured	0.767529	Binding	0.832	0.666	0.375											-2.295	Likely Benign	0.689	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-3.24	Deleterious	0.905	Possibly Damaging	0.433	Benign	2.07	Pathogenic	0.00	Affected			0.1780	0.5888		0	1	-0.4	-0.94
c.3812A>T	E1271V 2D AISynGAP1 missense variant E1271V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. Considering the majority of high‑confidence tools and the consensus score, the variant is most likely pathogenic. This assessment does not contradict any ClinVar annotation, as no ClinVar entry exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.767529	Binding	0.832	0.666	0.375											-6.961	Likely Benign	0.848	Likely Pathogenic	Ambiguous										0.303	Likely Benign	-5.64	Deleterious	0.995	Probably Damaging	0.846	Possibly Damaging	2.02	Pathogenic	0.00	Affected			0.0620	0.6106		-2	-2	7.7	-29.98
c.3814G>A	E1272K 2D AIThe SynGAP1 E1272K missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are made by REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-4.227	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.312	Likely Benign	-3.37	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1544	0.5488		0	1	-0.4	-0.94
c.3814G>C	E1272Q 2D AIThe SynGAP1 E1272Q missense variant is catalogued in gnomAD (variant ID 6‑33447862‑G‑C) but has no ClinVar entry. Prediction tools cluster into two groups: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, a majority‑vote aggregator of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this assessment 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		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500								6-33447862-G-C	1	6.45e-7	-3.000	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.207	Likely Benign	-2.53	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.25	Pathogenic	0.00	Affected	3.77	5	0.0746	0.5258		2	2	0.0	-0.98
c.3815A>C	E1272A 2D AIThe SynGAP1 missense variant E1272A 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for E1272A. 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		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-0.783	Likely Benign	0.779	Likely Pathogenic	Likely Benign										0.261	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.3243	0.5547		0	-1	5.3	-58.04
c.3815A>G	E1272G 2D AIThe SynGAP1 missense variant E1272G is catalogued in gnomAD (ID 6‑33447863‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which is labeled Likely Pathogenic. The high‑accuracy AlphaMissense‑Optimized assessment is uncertain, and the Foldetta protein‑folding stability analysis is not available for this residue. Overall, the majority of evidence points toward a deleterious effect, so the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists for E1272G. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500								6-33447863-A-G			-1.919	Likely Benign	0.863	Likely Pathogenic	Ambiguous										0.287	Likely Benign	-5.89	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.22	Pathogenic	0.00	Affected	3.77	5	0.2804	0.5072		-2	0	3.1	-72.06
c.3815A>T	E1272V 2D AIThe SynGAP1 missense variant E1272V is 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 ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-3.628	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.278	Likely Benign	-5.90	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.0424	0.5894		-2	-2	7.7	-29.98
c.3816G>C	E1272D 2D AIThe SynGAP1 missense variant E1272D has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments further show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect. There is no ClinVar classification to contradict this conclusion, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-4.781	Likely Benign	0.751	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.1450	0.3471		2	3	0.0	-14.03
c.3816G>T	E1272D 2D AIThe SynGAP1 missense variant E1272D is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33447864‑G‑T). Functional prediction tools show mixed results: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized tool classifies the change as benign, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. No Foldetta stability assessment is available for this variant. Overall, the majority of conventional predictors and the consensus score lean toward pathogenicity, which is consistent with the SGM‑Consensus designation but contradicts the benign calls from AlphaMissense‑Optimized and a few other tools. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion aligns with the SGM‑Consensus prediction rather than the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500								6-33447864-G-T			-4.781	Likely Benign	0.751	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.1450	0.3471		2	3	0.0	-14.03
c.3818T>A	L1273Q 2D AIThe SynGAP1 missense variant L1273Q 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic and the SGM‑Consensus is labeled Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500											-6.813	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.423	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.950	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1139	0.1119		-2	-2	-7.3	14.97
c.3818T>C	L1273P 2D AIThe SynGAP1 missense variant L1273P is not reported in ClinVar (ClinVar status: not listed) but is present in the gnomAD database (gnomAD ID: 6‑33447866‑T‑C). Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the consensus of predictive algorithms strongly supports a pathogenic classification, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500								6-33447866-T-C			-9.443	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.523	Likely Pathogenic	-5.87	Deleterious	0.997	Probably Damaging	0.950	Probably Damaging	2.12	Pathogenic	0.00	Affected	3.77	5	0.3836	0.1343		-3	-3	-5.4	-16.04
c.3818T>G	L1273R 2D AIThe SynGAP1 missense variant L1273R 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 ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment is not contradicted by any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500											-6.252	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.431	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.934	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1369	0.0761		-3	-2	-8.3	43.03
c.3820C>G	R1274G 2D AIThe SynGAP1 R1274G 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and therefore predicts a pathogenic outcome. AlphaMissense‑Optimized alone predicts benign, while Foldetta results are unavailable. Overall, the majority of evidence (seven pathogenic versus 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.	Likely Pathogenic		0.613573	Disordered	0.779985	Binding	0.746	0.688	0.625											-3.288	Likely Benign	0.579	Likely Pathogenic	Likely Benign										0.145	Likely Benign	-4.36	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	2.49	Pathogenic	0.01	Affected			0.3316	0.2310		-3	-2	4.1	-99.14
c.3821G>C	R1274P 2D AIThe SynGAP1 missense variant R1274P 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 ESM1b, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that R1274P is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.613573	Disordered	0.779985	Binding	0.746	0.688	0.625											-6.145	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.179	Likely Benign	-4.02	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.48	Pathogenic	0.01	Affected			0.2166	0.3095		0	-2	2.9	-59.07
c.3826G>C	D1276H 2D AIThe SynGAP1 missense variant D1276H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates majority votes from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further highlight discordance: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus (a high‑accuracy consensus) 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 support a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625											0.715	Likely Benign	0.778	Likely Pathogenic	Likely Benign										0.321	Likely Benign	-5.08	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	1.19	Pathogenic	0.00	Affected			0.1077	0.5697		1	-1	0.3	22.05
c.3826G>T	D1276Y 2D AIThe SynGAP1 missense variant D1276Y is catalogued in gnomAD (ID 6‑33447874‑G‑T) but has no ClinVar entry. Functional prediction tools fall into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic effect; Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status, as none is currently reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625								6-33447874-G-T			-1.558	Likely Benign	0.768	Likely Pathogenic	Likely Benign										0.325	Likely Benign	-6.66	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	1.18	Pathogenic	0.00	Affected	3.77	5	0.0385	0.5082		-3	-4	2.2	48.09
c.3827A>C	D1276A 2D AIThe SynGAP1 missense variant D1276A has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support this split: AlphaMissense‑Optimized reports a benign effect, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. No Foldetta stability analysis is available for this residue. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625											-0.008	Likely Benign	0.710	Likely Pathogenic	Likely Benign										0.319	Likely Benign	-5.87	Deleterious	0.816	Possibly Damaging	0.495	Possibly Damaging	1.21	Pathogenic	0.00	Affected			0.3458	0.5050		0	-2	5.3	-44.01
c.3827A>G	D1276G 2D AIThe SynGAP1 missense variant D1276G 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, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions and the SGM‑Consensus support a pathogenic interpretation, and there is no ClinVar record to contradict this assessment. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625											0.509	Likely Benign	0.601	Likely Pathogenic	Likely Benign										0.293	Likely Benign	-4.93	Deleterious	0.899	Possibly Damaging	0.655	Possibly Damaging	1.21	Pathogenic	0.00	Affected			0.3429	0.5247		1	-1	3.1	-58.04
c.3827A>T	D1276V 2D AIThe SynGAP1 D1276V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625											-0.725	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.331	Likely Benign	-6.66	Deleterious	0.984	Probably Damaging	0.825	Possibly Damaging	1.19	Pathogenic	0.00	Affected			0.0614	0.5207		-2	-3	7.7	-15.96
c.3863A>T	K1288M 2D AIThe SynGAP1 missense variant K1288M is 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 AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of computational predictions (seven pathogenic vs. three benign) point to a pathogenic impact for K1288M. 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		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.355	Likely Benign	0.660	Likely Pathogenic	Likely Benign										0.246	Likely Benign	-4.89	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.0985	0.3140		0	-1	5.8	3.02
c.3864G>C	K1288N 2D AIThe SynGAP1 missense variant K1288N has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no result for this variant. High‑accuracy assessments therefore show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3864G>T	K1288N 2D AIThe SynGAP1 missense variant K1288N 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 ESM1b, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy assessments therefore show an uncertain AlphaMissense‑Optimized prediction, a Likely Pathogenic SGM‑Consensus, and no Foldetta data. Overall, the preponderance of evidence points to a pathogenic impact, 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		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3885G>C	Q1295H 2D AIThe SynGAP1 missense variant Q1295H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625											-4.851	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.349	Likely Benign	-4.08	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.1345	0.3203		3	0	0.3	9.01
c.3885G>T	Q1295H 2D AIThe SynGAP1 missense variant Q1295H is catalogued in gnomAD (ID 6‑33447933‑G‑T) but has no ClinVar submission. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. When predictions are grouped, 3 tools predict benign and 6 predict pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this substitution. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625								6-33447933-G-T			-4.851	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.349	Likely Benign	-4.08	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.1345	0.3203		3	0	0.3	9.01
c.391G>T	G131C 2D AIThe SynGAP1 missense variant G131C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas 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, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus again indicates Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of tools predict pathogenicity, and this aligns with the SGM Consensus. Therefore, the variant is most likely pathogenic based on the available predictions, and this conclusion is consistent with the lack of ClinVar reporting rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.724779	Binding	0.302	0.891	0.250											-8.288	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign										0.155	Likely Benign	-4.42	Deleterious	0.998	Probably Damaging	0.840	Possibly Damaging	3.88	Benign	0.00	Affected			0.1339	0.4356		-3	-3	2.9	46.09
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.398T>A	L133Q 2D AIThe SynGAP1 missense variant L133Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-9.054	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-2.65	Deleterious	0.535	Possibly Damaging	0.259	Benign	3.53	Benign	0.01	Affected			0.1316	0.0879		-2	-2	-7.3	14.97
c.398T>G	L133R 2D AIThe SynGAP1 missense variant L133R 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. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome (3 pathogenic vs. 1 benign votes). AlphaMissense‑Optimized independently predicts pathogenicity. 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 supports a pathogenic classification for L133R, and this assessment does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-8.857	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.389	Likely Benign	-2.57	Deleterious	0.002	Benign	0.005	Benign	3.55	Benign	0.00	Affected			0.1522	0.0479		-3	-2	-8.3	43.03
c.4003G>A	G1335S 2D AIThe SynGAP1 missense variant G1335S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33451877‑G‑A). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all 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, PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that G1335S is most likely pathogenic, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750					Conflicting		2	6-33451877-G-A	3	2.37e-6	-4.495	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.362	Likely Benign	-3.79	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.04	Pathogenic	0.00	Affected	3.77	5	0.2452	0.5895		1	0	-0.4	30.03
c.4003G>C	G1335R 2D AIThe SynGAP1 missense variant G1335R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available. Overall, the preponderance of evidence supports a pathogenic classification for G1335R, 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		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750											-4.921	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.394	Likely Benign	-5.06	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1071	0.5024		-3	-2	-4.1	99.14
c.4003G>T	G1335C 2D AIThe SynGAP1 missense variant G1335C is listed in gnomAD (variant ID 6-33451877‑G‑T) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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 pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750								6-33451877-G-T	1	7.91e-7	-6.878	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.426	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.01	Pathogenic	0.00	Affected	3.77	5	0.1376	0.4513		-3	-3	2.9	46.09
c.4004G>A	G1335D 2D AIThe SynGAP1 missense variant G1335D is reported in ClinVar as “not listed” and is present in gnomAD (variant ID 6‑33451878‑G‑A). Functional prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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 Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the SGM‑Consensus suggests that G1335D 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		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750								6-33451878-G-A			-5.687	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.404	Likely Benign	-4.42	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.00	Affected	3.77	5	0.2120	0.3702		-1	1	-3.1	58.04
c.4004G>C	G1335A 2D AIThe SynGAP1 missense variant G1335A is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for G1335A, 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		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750											-4.942	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.357	Likely Benign	-3.69	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.05	Pathogenic	0.00	Affected			0.3383	0.4953		1	0	2.2	14.03
c.4004G>T	G1335V 2D AIThe SynGAP1 missense variant G1335V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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, 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 evidence points to a pathogenic impact, and this assessment does not conflict with the ClinVar status, which currently has no entry for G1335V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750											-4.982	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.394	Likely Benign	-5.65	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1124	0.4195		-1	-3	4.6	42.08
c.400A>C	S134R 2D AIThe SynGAP1 missense variant S134R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.053	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-2.54	Deleterious	0.380	Benign	0.147	Benign	3.84	Benign	0.00	Affected			0.0719	0.3528		0	-1	-3.7	69.11
c.400A>T	S134C 2D AIThe SynGAP1 missense variant S134C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen2_HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of tools and the consensus prediction lean toward pathogenicity, which is not contradicted by ClinVar (no entry) but is opposed by the AlphaMissense‑Optimized benign call. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.184	Likely Pathogenic	0.774	Likely Pathogenic	Likely Benign										0.247	Likely Benign	-3.12	Deleterious	0.876	Possibly Damaging	0.417	Benign	3.79	Benign	0.00	Affected			0.0767	0.5151		0	-1	3.3	16.06
c.401G>T	S134I 2D AIThe SynGAP1 missense variant S134I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-8.860	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.230	Likely Benign	-3.27	Deleterious	0.041	Benign	0.031	Benign	3.81	Benign	0.00	Affected			0.0683	0.5191		-1	-2	5.3	26.08
c.402C>A	S134R 2D AIThe SynGAP1 missense variant S134R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict pathogenicity are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.053	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.54	Deleterious	0.380	Benign	0.147	Benign	3.84	Benign	0.00	Affected			0.0719	0.3528		0	-1	-3.7	69.11
c.402C>G	S134R 2D AIThe SynGAP1 missense variant S134R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict pathogenicity are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-9.053	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.54	Deleterious	0.380	Benign	0.147	Benign	3.84	Benign	0.00	Affected			0.0719	0.3528		0	-1	-3.7	69.11
c.404G>C	R135P 2D AIThe SynGAP1 missense variant R135P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors that classify the variant as benign include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy tools give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment 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		0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-9.512	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.139	Likely Benign	-3.19	Deleterious	0.609	Possibly Damaging	0.308	Benign	3.68	Benign	0.01	Affected			0.2052	0.4535		0	-2	2.9	-59.07
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.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.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.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.410T>A	L137Q 2D AIThe SynGAP1 missense variant L137Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated algorithms—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 a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-12.246	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.356	Likely Benign	-3.43	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.60	Benign	0.00	Affected			0.1137	0.1049		-2	-2	-7.3	14.97
c.410T>C	L137P 2D AIThe SynGAP1 missense variant L137P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-11.067	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.377	Likely Benign	-3.77	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.59	Benign	0.00	Affected			0.3620	0.1177		-3	-3	-5.4	-16.04
c.410T>G	L137R 2D AIThe SynGAP1 missense variant L137R 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. All other evaluated tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-11.595	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.334	Likely Benign	-3.50	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.60	Benign	0.00	Affected			0.1300	0.0691		-3	-2	-8.3	43.03
c.413A>T	K138I 2D AIThe SynGAP1 missense variant K138I 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 outcome: 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 is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-9.366	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.295	Likely Benign	-4.74	Deleterious	0.535	Possibly Damaging	0.259	Benign	3.53	Benign	0.00	Affected			0.1003	0.3054		-2	-3	8.4	-15.01
c.416G>T	S139I 2D AIThe SynGAP1 missense variant S139I 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 come from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect. 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		0.553315	Disordered	0.600637	Binding	0.353	0.900	0.250											-9.228	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.203	Likely Benign	-3.36	Deleterious	0.380	Benign	0.102	Benign	4.09	Benign	0.03	Affected			0.0948	0.4796		-1	-2	5.3	26.08
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>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.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.422T>A	I141N 2D AIThe SynGAP1 missense variant I141N is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions 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 stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for I141N. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-12.417	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.258	Likely Benign	-3.90	Deleterious	0.799	Possibly Damaging	0.424	Benign	3.54	Benign	0.00	Affected			0.1047	0.0270		-2	-3	-8.0	0.94
c.422T>C	I141T 2D AIThe SynGAP1 missense variant I141T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its contribution is unavailable. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-10.580	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.251	Likely Benign	-2.81	Deleterious	0.272	Benign	0.167	Benign	3.57	Benign	0.00	Affected			0.1165	0.1214		0	-1	-5.2	-12.05
c.422T>G	I141S 2D AIThe SynGAP1 missense variant I141S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus also as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for I141S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-11.874	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.267	Likely Benign	-3.28	Deleterious	0.567	Possibly Damaging	0.249	Benign	3.56	Benign	0.00	Affected			0.2885	0.0840		-1	-2	-5.3	-26.08
c.424A>C	K142Q 2D AIThe SynGAP1 missense variant K142Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-11.295	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-2.50	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.50	Benign	0.00	Affected			0.4232	0.1132		1	1	0.4	-0.04
c.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.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.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.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.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.428G>C	R143P 2D AIThe SynGAP1 missense variant R143P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta stability analysis is unavailable. Overall, the majority of computational evidence points to a pathogenic impact, and this is consistent with the ClinVar designation of “Uncertain” rather than contradicting it. 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		2	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.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.430A>C	T144P 2D AIThe SynGAP1 missense variant T144P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict pathogenicity are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of predictions and the consensus call indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-11.920	Likely Pathogenic	0.775	Likely Pathogenic	Likely Benign										0.159	Likely Benign	-2.66	Deleterious	0.000	Benign	0.000	Benign	3.76	Benign	0.00	Affected			0.2508	0.5271		0	-1	-0.9	-3.99