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

c.dna	Variant	SGM Consensus	Domain and Structure information: based on WT protein												Annotated databases						Deep learning-based pathogenicity predictions					Folding stability-based pathogenicity predictions									Sequence/structure-based pathogenicity predictions														Phase Separation			Evolutionary/physical properties				Molecular Dynamics-based analysis															DOI
			Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	PhosphoSitePlus				ClinVar			gnomAD			ESM1b		AlphaMissense			FoldX			Rosetta		Foldetta		PremPS		REVEL		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PSMutPred			PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	LTP	HTP	KL	PTM	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	IP RF	SP RF	Prediction	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.529T>G	F177V 2D AIThe SynGAP1 missense variant F177V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of standard predictors favor a benign outcome, but the optimized AlphaMissense model and ESM1b suggest potential pathogenicity. Thus, the variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-11.582	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-1.26	Neutral	0.028	Benign	0.009	Benign	4.18	Benign	0.06	Tolerated			0.2454	0.3526		-1	-1	1.4	-48.04
c.61T>G	F21V 2D AIThe SynGAP1 missense variant F21V is listed in gnomAD (ID 6‑33420325‑T‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420325-T-G			-2.823	Likely Benign	0.563	Ambiguous	Likely Benign										0.224	Likely Benign	0.64	Neutral	0.462	Possibly Damaging	0.307	Benign	4.44	Benign	0.00	Affected	4.32	1	0.2536	0.2497		-1	-1	1.4	-48.04
c.652T>G	F218V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; pathogenic predictions arise from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus agrees on a likely pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenicity. No predictions or stability results are missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion aligns with the absence of a ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000											-10.081	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	4.18	Destabilizing	0.2	6.35	Destabilizing	5.27	Destabilizing	1.15	Destabilizing	0.691	Likely Pathogenic	-4.14	Deleterious	0.300	Benign	0.066	Benign	5.81	Benign	0.08	Tolerated			0.2173	0.2258		-1	-1	1.4	-48.04
c.658T>G	F220V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F220V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments further support a deleterious impact: 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 outputs, is pathogenic. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.219301	Structured	0.429422	Uncertain	0.898	0.295	0.000											-11.599	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.83	Destabilizing	0.1	4.11	Destabilizing	3.97	Destabilizing	1.56	Destabilizing	0.911	Likely Pathogenic	-5.81	Deleterious	0.075	Benign	0.015	Benign	4.04	Benign	0.01	Affected			0.2351	0.3315		-1	-1	1.4	-48.04
c.691T>G	F231V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are polyPhen‑2 HumVar and FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also indicates pathogenicity. Taken together, the evidence overwhelmingly points to a pathogenic effect for F231V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000											-13.201	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.3	2.30	Destabilizing	2.23	Destabilizing	1.13	Destabilizing	0.910	Likely Pathogenic	-5.90	Deleterious	0.759	Possibly Damaging	0.328	Benign	5.72	Benign	0.00	Affected			0.2212	0.3030		-1	-1	1.4	-48.04
c.919T>G	F307V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307V is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include Rosetta and premPS, whereas the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the consensus score SGM‑Consensus all classify the change as pathogenic or likely pathogenic. High‑accuracy methods give a pathogenic call from AlphaMissense‑Optimized, a likely pathogenic result from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and an inconclusive result from Foldetta (combining FoldX‑MD and Rosetta). No prediction is missing or inconclusive enough to alter the overall assessment. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-12.262	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	0.10	Likely Benign	0.51	Ambiguous	0.36	Likely Benign	0.605	Likely Pathogenic	-6.43	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.29	Pathogenic	0.05	Affected			0.2523	0.3393		-1	-1	1.4	-48.04
c.934T>G	F312V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312V is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the change as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Based on the unanimous 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	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-12.206	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	2.13	Destabilizing	0.1	3.46	Destabilizing	2.80	Destabilizing	1.80	Destabilizing	0.877	Likely Pathogenic	-6.43	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.25	Pathogenic	0.00	Affected			0.1998	0.2810		-1	-1	1.4	-48.04
c.940T>G	F314V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). All available in silico predictors classify the variant as pathogenic: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta—each return a pathogenic prediction. No predictions or stability results are missing or inconclusive. Based on the unanimous 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	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-8.907	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	3.31	Destabilizing	0.4	2.54	Destabilizing	2.93	Destabilizing	1.44	Destabilizing	0.594	Likely Pathogenic	-5.90	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.26	Pathogenic	0.00	Affected			0.2054	0.2075		-1	-1	1.4	-48.04
c.1189T>G	C397G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus all indicate a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies it as “Likely Benign.” No tool predicts pathogenicity. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No pathogenic predictions are present. Therefore, based on the available computational evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.429200	Structured	0.395774	Uncertain	0.778	0.551	0.250											1.244	Likely Benign	0.096	Likely Benign	Likely Benign	0.68	Ambiguous	0.2	1.42	Ambiguous	1.05	Ambiguous	0.04	Likely Benign	0.272	Likely Benign	1.51	Neutral	0.276	Benign	0.066	Benign	5.93	Benign	0.60	Tolerated			0.3678	0.3729		-3	-3	-2.9	-46.09
c.1294T>G	C432G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-10.247	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	1.37	Ambiguous	0.0	2.25	Destabilizing	1.81	Ambiguous	1.60	Destabilizing	0.631	Likely Pathogenic	-11.46	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.03	Affected			0.2796	0.2130		-3	-3	-2.9	-46.09
c.145T>G	C49G 2D AIThe SynGAP1 missense variant C49G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic versus four benign) lean toward a pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.464	Likely Benign	0.674	Likely Pathogenic	Likely Benign										0.351	Likely Benign	-3.64	Deleterious	0.462	Possibly Damaging	0.599	Possibly Damaging	3.87	Benign	0.00	Affected			0.2419	0.2528		-3	-3	-2.9	-46.09
c.1570T>G	C524G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change at residue 524 (C524G) is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while FoldX and Foldetta are uncertain. No tool predicts a benign effect. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the evidence strongly favors a pathogenic impact for C524G, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125											-13.597	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.2	2.00	Destabilizing	1.54	Ambiguous	1.66	Destabilizing	0.924	Likely Pathogenic	-11.93	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.40	Pathogenic	0.00	Affected			0.3579	0.2745		-3	-3	-2.9	-46.09
c.1591T>G	C531G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX and AlphaMissense‑Optimized, while the majority of other in silico predictors (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) indicate a pathogenic impact. Uncertain results come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the balance of evidence leans toward pathogenicity, with no ClinVar entry to contradict this assessment. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-10.037	Likely Pathogenic	0.577	Likely Pathogenic	Likely Benign	0.47	Likely Benign	0.3	1.49	Ambiguous	0.98	Ambiguous	1.42	Destabilizing	0.545	Likely Pathogenic	-9.76	Deleterious	0.985	Probably Damaging	0.832	Possibly Damaging	-1.24	Pathogenic	0.00	Affected			0.2653	0.2297		-3	-3	-2.9	-46.09
c.1636T>G	C546G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C546G is not reported in ClinVar and is present in gnomAD (ID 6‑33438879‑T‑G). Prediction tools that indicate a benign effect include only SIFT, whereas the remaining tools—REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is inconclusive and therefore not considered evidence. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000								6-33438879-T-G	1	6.20e-7	-14.026	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.0	2.43	Destabilizing	1.99	Ambiguous	1.53	Destabilizing	0.877	Likely Pathogenic	-9.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.26	Pathogenic	0.06	Tolerated	3.37	35	0.3135	0.2513		-3	-3	-2.9	-46.09
c.1639T>G	C547G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenic. No tool predicts a benign outcome. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support a harmful impact: 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, predicts a pathogenic effect. Taken together, the evidence overwhelmingly points to a pathogenic classification for this variant, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-14.182	Likely Pathogenic	0.923	Likely Pathogenic	Ambiguous	2.21	Destabilizing	0.0	2.99	Destabilizing	2.60	Destabilizing	1.83	Destabilizing	0.902	Likely Pathogenic	-11.60	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.30	Pathogenic	0.05	Affected			0.3201	0.2502		-3	-3	-2.9	-46.09
c.1654T>G	C552G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552G is not reported in ClinVar and is absent from gnomAD. In silico predictors that classify the change as benign include FoldX, Rosetta, Foldetta, and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy subset shows AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With six pathogenic versus four benign predictions overall, the evidence leans toward a deleterious effect. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-11.570	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.0	0.29	Likely Benign	0.28	Likely Benign	1.06	Destabilizing	0.745	Likely Pathogenic	-10.20	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.21	Pathogenic	0.35	Tolerated			0.2338	0.1930		-3	-3	-2.9	-46.09
c.1675T>G	C559G 2D 3DClick to see structure in 3D Viewer AISynGAP1 C559G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Foldetta, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain calls from Rosetta and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (seven pathogenic vs five benign) and the high‑accuracy consensus lean toward a pathogenic effect. This conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000											-12.342	Likely Pathogenic	0.581	Likely Pathogenic	Likely Benign	0.12	Likely Benign	0.1	0.53	Ambiguous	0.33	Likely Benign	0.76	Ambiguous	0.547	Likely Pathogenic	-8.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.50	Benign	0.37	Tolerated			0.2454	0.2001		-3	-3	-2.9	-46.09
c.1726T>G	C576G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome. When high‑accuracy methods are considered, AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenicity. No prediction is inconclusive or missing. Consequently, the variant is most likely pathogenic based on the consensus of available computational evidence, and this assessment does not contradict any ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-14.809	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.0	2.53	Destabilizing	2.10	Destabilizing	1.67	Destabilizing	0.586	Likely Pathogenic	-10.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.00	Affected			0.3269	0.2574		-3	-3	-2.9	-46.09
c.1795T>G	C599G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the evidence strongly favors a pathogenic effect, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.342	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	1.40	Ambiguous	0.0	0.90	Ambiguous	1.15	Ambiguous	1.43	Destabilizing	0.923	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.50	Pathogenic	0.03	Affected			0.2444	0.2130		-3	-3	-2.9	-46.09
c.2461T>G	C821G 2D AIThe SynGAP1 missense variant C821G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.613	Likely Benign	0.910	Likely Pathogenic	Ambiguous										0.187	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.05	Affected			0.3287	0.2747		-3	-3	-2.9	-46.09
c.655T>G	C219G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining 11 tools—including REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized returns a pathogenic score, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is inconclusive. Taken together, the overwhelming majority of evidence points to a pathogenic effect for C219G. This conclusion aligns 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	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000											-15.072	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.3	1.98	Ambiguous	1.35	Ambiguous	1.18	Destabilizing	0.900	Likely Pathogenic	-10.09	Deleterious	0.900	Possibly Damaging	0.461	Possibly Damaging	5.83	Benign	0.02	Affected			0.2159	0.2169		-3	-3	-2.9	-46.09
c.688T>G	C230G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reached a consensus fall into two groups: benign predictions come from polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or inconclusive results from FoldX, Rosetta, Foldetta, and premPS are treated as unavailable and do not influence the overall assessment. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also Likely Pathogenic; Foldetta remains uncertain. Based on the aggregate predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-10.888	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	0.86	Ambiguous	0.79	Ambiguous	0.81	Ambiguous	0.775	Likely Pathogenic	-9.95	Deleterious	0.001	Benign	0.004	Benign	5.85	Benign	0.03	Affected			0.3313	0.2574		-3	-3	-2.9	-46.09
c.697T>G	C233G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233G 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 polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy predictions: AlphaMissense‑Optimized reports Pathogenic; SGM‑Consensus reports Likely Pathogenic; Foldetta is Uncertain. Overall, the majority of available predictions indicate a pathogenic impact. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-14.155	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	1.29	Ambiguous	0.1	1.01	Ambiguous	1.15	Ambiguous	1.31	Destabilizing	0.849	Likely Pathogenic	-10.68	Deleterious	0.596	Possibly Damaging	0.107	Benign	5.79	Benign	0.09	Tolerated			0.3317	0.3570		-3	-3	-2.9	-46.09
c.844T>G	C282G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282G is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus is pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among pathogenic predictors and the high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-15.830	Likely Pathogenic	0.837	Likely Pathogenic	Ambiguous	2.60	Destabilizing	0.1	2.83	Destabilizing	2.72	Destabilizing	1.60	Destabilizing	0.482	Likely Benign	-11.03	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.64	Pathogenic	0.04	Affected			0.3229	0.2238		-3	-3	-2.9	-46.09
c.853T>G	C285G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a pathogenic interpretation: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict deleterious effects. Tools that assess protein stability (FoldX, Rosetta, Foldetta) and AlphaMissense‑Optimized return uncertain results, providing no clear evidence for or against pathogenicity. High‑accuracy assessments further support a likely pathogenic verdict: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the consensus of the majority of predictors indicates that the variant is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000											-9.937	Likely Pathogenic	0.859	Likely Pathogenic	Ambiguous	1.26	Ambiguous	0.0	1.57	Ambiguous	1.42	Ambiguous	1.50	Destabilizing	0.564	Likely Pathogenic	-9.86	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.78	Pathogenic	0.04	Affected			0.3509	0.2922		-3	-3	-2.9	-46.09
c.1073T>G	F358C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F358C is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls arise from Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is inconclusive, Foldetta is inconclusive, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenic. Because the majority of available predictions favor a damaging effect, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.966	In-Between	0.927	Likely Pathogenic	Ambiguous	1.68	Ambiguous	0.1	2.19	Destabilizing	1.94	Ambiguous	1.18	Destabilizing	0.460	Likely Benign	-6.36	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	4.02	Benign	0.06	Tolerated			0.2364	0.1800		-4	-2	-0.3	-44.04
c.1259T>G	F420C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420C is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity largely agree: 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. When grouped by consensus, the benign prediction is singular (FATHMM), whereas the pathogenic predictions comprise the remaining eleven tools. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions are missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-11.931	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.31	Destabilizing	0.1	5.11	Destabilizing	4.71	Destabilizing	2.49	Destabilizing	0.500	Likely Pathogenic	-7.40	Deleterious	0.998	Probably Damaging	0.869	Possibly Damaging	3.09	Benign	0.00	Affected			0.2458	0.0662		-4	-2	-0.3	-44.04
c.1391T>G	F464C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-13.011	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.18	Destabilizing	0.0	4.31	Destabilizing	4.25	Destabilizing	2.20	Destabilizing	0.740	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.26	Benign	0.00	Affected			0.2298	0.1219		-4	-2	-0.3	-44.04
c.1427T>G	F476C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476C is catalogued in gnomAD (ID 6‑33438459‑T‑G) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, seven tools predict pathogenicity versus six predicting benign, with no ClinVar evidence to contradict this assessment. Thus, the variant is most likely pathogenic based on the current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000								6-33438459-T-G			-9.270	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	2.05	Destabilizing	0.1	2.62	Destabilizing	2.34	Destabilizing	-0.30	Likely Benign	0.280	Likely Benign	2.69	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	3.46	Benign	0.83	Tolerated	3.40	22	0.2051	0.1251		-2	-4	-0.3	-44.04
c.143T>G	F48C 2D AIThe SynGAP1 missense variant F48C 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, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (3 benign vs. 1 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-5.950	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.153	Likely Benign	-2.31	Neutral	0.953	Possibly Damaging	0.431	Benign	3.93	Benign	0.00	Affected			0.2657	0.1962		-4	-2	-0.3	-44.04
c.1451T>G	F484C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484C 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 this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. 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 (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-14.988	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	4.01	Destabilizing	0.0	3.54	Destabilizing	3.78	Destabilizing	2.07	Destabilizing	0.675	Likely Pathogenic	-7.73	Deleterious	1.000	Probably Damaging	0.969	Probably Damaging	2.66	Benign	0.00	Affected			0.2449	0.0902		-4	-2	-0.3	-44.04
c.1538T>G	F513C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513C is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also labels it pathogenic. Based on the uniform predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-11.389	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	3.92	Destabilizing	0.3	4.20	Destabilizing	4.06	Destabilizing	1.64	Destabilizing	0.919	Likely Pathogenic	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.40	Pathogenic	0.03	Affected			0.2384	0.0783		-4	-2	-0.3	-44.04
c.1682T>G	F561C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561C 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 SIFT, whereas all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious 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 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 any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-13.035	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.92	Destabilizing	0.0	3.99	Destabilizing	3.96	Destabilizing	1.22	Destabilizing	0.769	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.25	Pathogenic	0.15	Tolerated			0.2720	0.0615		-4	-2	-0.3	-44.04
c.1706T>G	F569C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569C is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also labels it pathogenic. Based on the uniform predictions, the variant is most likely pathogenic, and this 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	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-13.237	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	4.08	Destabilizing	0.0	4.45	Destabilizing	4.27	Destabilizing	1.20	Destabilizing	0.867	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.96	Pathogenic	0.04	Affected			0.2722	0.0462		-4	-2	-0.3	-44.04
c.1781T>G	F594C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594C is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. All available evidence points to a damaging effect. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-14.591	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.0	4.35	Destabilizing	4.16	Destabilizing	1.36	Destabilizing	0.943	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-2.05	Pathogenic	0.03	Affected			0.2595	0.0615		-4	-2	-0.3	-44.04
c.1790T>G	F597C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F597C is reported in gnomAD (variant ID 6-33440842‑T‑G) but has no ClinVar entry. Functional prediction tools uniformly indicate a deleterious effect: 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 outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000								6-33440842-T-G	1	6.19e-7	-12.099	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.77	Destabilizing	0.2	4.17	Destabilizing	3.97	Destabilizing	1.97	Destabilizing	0.953	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-2.19	Pathogenic	0.00	Affected	3.37	35	0.2618	0.0783		-2	-4	-0.3	-44.04
c.1823T>G	F608C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608C is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classifies the change as pathogenic; no tool predicts a benign effect. High‑accuracy methods reinforce this consensus: 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 reports a pathogenic effect. Because all evidence points to a deleterious impact and there is no ClinVar entry to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-14.409	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	2.46	Destabilizing	0.2	3.04	Destabilizing	2.75	Destabilizing	1.77	Destabilizing	0.920	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.67	Pathogenic	0.00	Affected			0.2738	0.1050		-4	-2	-0.3	-44.04
c.1907T>G	F636C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636C is reported in gnomAD (ID 6‑33440959‑T‑G) but has no ClinVar entry. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Only FATHMM predicts a benign outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000								6-33440959-T-G	3	1.86e-6	-13.287	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.1	2.65	Destabilizing	2.20	Destabilizing	1.22	Destabilizing	0.612	Likely Pathogenic	-7.67	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.40	Benign	0.04	Affected	3.37	34	0.2301	0.0830		-2	-4	-0.3	-44.04
c.1916T>G	F639C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F639C 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, and ESM1b all indicate pathogenicity, while only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-12.532	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	4.02	Destabilizing	0.2	2.80	Destabilizing	3.41	Destabilizing	1.38	Destabilizing	0.615	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	0.935	Probably Damaging	3.05	Benign	0.01	Affected			0.2451	0.0783		-4	-2	-0.3	-44.04
c.1934T>G	F645C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of tools predict a pathogenic outcome: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-9.182	Likely Pathogenic	0.828	Likely Pathogenic	Ambiguous	2.25	Destabilizing	0.1	2.44	Destabilizing	2.35	Destabilizing	1.38	Destabilizing	0.286	Likely Benign	-5.41	Deleterious	0.967	Probably Damaging	0.389	Benign	3.35	Benign	0.01	Affected			0.2421	0.1372		-4	-2	-0.3	-44.04
c.1943T>G	F648C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools largely agree on a deleterious effect: all evaluated algorithms except FATHMM predict pathogenicity, while FATHMM alone predicts benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a pathogenic effect. In summary, the overwhelming consensus from both general and high‑accuracy predictors is that F648C is pathogenic. This conclusion is consistent with the absence of any ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-10.547	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.28	Destabilizing	0.1	3.35	Destabilizing	3.32	Destabilizing	1.22	Destabilizing	0.621	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.40	Benign	0.03	Affected			0.2283	0.0783		-4	-2	-0.3	-44.04
c.1955T>G	F652C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F652C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. No prediction is inconclusive or missing. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.356594	Uncertain	0.966	0.338	0.000											-12.023	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.27	Destabilizing	0.1	4.35	Destabilizing	3.81	Destabilizing	2.54	Destabilizing	0.695	Likely Pathogenic	-7.74	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.99	Benign	0.00	Affected			0.2293	0.0783		-4	-2	-0.3	-44.04
c.1988T>G	F663C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this 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	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-13.544	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.83	Destabilizing	0.1	4.54	Destabilizing	4.19	Destabilizing	1.91	Destabilizing	0.772	Likely Pathogenic	-7.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.96	Benign	0.00	Affected			0.2343	0.0783		-4	-2	-0.3	-44.04
c.2036T>G	F679C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679C has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. FoldX and Foldetta are uncertain and are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta remains inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for F679C. This prediction is not contradicted by ClinVar status, which currently lacks any classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-10.269	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.65	Ambiguous	0.3	2.02	Destabilizing	1.84	Ambiguous	1.17	Destabilizing	0.532	Likely Pathogenic	-7.86	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.40	Benign	0.00	Affected			0.2344	0.0949		-4	-2	-0.3	-44.04
c.2315T>G	F772C 2D AIThe SynGAP1 missense variant F772C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-4.498	Likely Benign	0.248	Likely Benign	Likely Benign										0.156	Likely Benign	-1.46	Neutral	0.979	Probably Damaging	0.985	Probably Damaging	4.14	Benign	0.10	Tolerated			0.2450	0.1419		-4	-2	-0.3	-44.04
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.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.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.2927T>G	F976C 2D AIThe SynGAP1 missense variant F976C is not reported in ClinVar and is absent from gnomAD. In silico predictors cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for F976C, and this conclusion is not in conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625											-5.490	Likely Benign	0.490	Ambiguous	Likely Benign										0.103	Likely Benign	-1.10	Neutral	0.977	Probably Damaging	0.840	Possibly Damaging	4.09	Benign	0.10	Tolerated			0.2961	0.2505		-4	-2	-0.3	-44.04
c.2936T>G	F979C 2D AIThe SynGAP1 missense variant F979C is not reported in ClinVar and has no gnomAD entry. Consensus from high‑accuracy predictors is benign: AlphaMissense‑Optimized scores it benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign. Other tools that agree with benign include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, did not return a result for this variant, so its stability impact is unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625											-6.395	Likely Benign	0.589	Likely Pathogenic	Likely Benign										0.160	Likely Benign	-0.94	Neutral	0.994	Probably Damaging	0.888	Possibly Damaging	4.15	Benign	0.00	Affected			0.2646	0.2179		-4	-2	-0.3	-44.04
c.3029T>G	F1010C 2D AIThe SynGAP1 missense variant F1010C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-4.442	Likely Benign	0.755	Likely Pathogenic	Likely Benign										0.153	Likely Benign	-2.31	Neutral	1.000	Probably Damaging	0.961	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.2646	0.1605		-4	-2	-0.3	-44.04
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.377T>G	F126C 2D AIThe SynGAP1 missense variant F126C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools predict pathogenicity (five) than benignity (three), and no ClinVar evidence contradicts this assessment. 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.			0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-2.553	Likely Benign	0.824	Likely Pathogenic	Ambiguous										0.109	Likely Benign	-3.19	Deleterious	0.952	Possibly Damaging	0.570	Possibly Damaging	3.88	Benign	0.00	Affected			0.2682	0.1270		-4	-2	-0.3	-44.04
c.395T>G	F132C 2D AIThe SynGAP1 missense variant F132C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from the four high‑accuracy predictors) also indicates likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-10.013	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.331	Likely Benign	-4.55	Deleterious	0.938	Possibly Damaging	0.498	Possibly Damaging	3.29	Benign	0.00	Affected			0.2677	0.0925		-4	-2	-0.3	-44.04
c.4010T>G	F1337C 2D AIThe SynGAP1 missense variant F1337C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625											-4.628	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.357	Likely Benign	-4.57	Deleterious	0.996	Probably Damaging	0.984	Probably Damaging	2.73	Benign	0.00	Affected			0.2619	0.1905		-4	-2	-0.3	-44.04
c.467T>G	F156C 2D AIThe SynGAP1 missense variant F156C is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional 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 from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as “Likely Pathogenic.” No Foldetta stability analysis is available for this variant. Overall, the majority of predictions, including the high‑accuracy tools, indicate that F156C 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		0.476583	Structured	0.521964	Binding	0.284	0.785	0.500					Uncertain		1				-13.658	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.297	Likely Benign	-3.54	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	3.92	Benign	0.00	Affected			0.3030	0.1291		-4	-2	-0.3	-44.04
c.488T>G	F163C 2D AIThe SynGAP1 missense variant F163C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv 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 this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates a likely pathogenic status. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of predictions, including the high‑accuracy tools, point 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		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-12.221	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-2.99	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	4.01	Benign	0.00	Affected			0.2860	0.1232		-4	-2	-0.3	-44.04
c.530T>G	F177C 2D AIThe SynGAP1 missense variant F177C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six pathogenic vs three benign) indicate a pathogenic impact. 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.			0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-11.487	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.241	Likely Benign	-2.20	Neutral	0.983	Probably Damaging	0.635	Possibly Damaging	4.07	Benign	0.01	Affected			0.2797	0.2539		-4	-2	-0.3	-44.04
c.62T>G	F21C 2D AIThe SynGAP1 missense variant F21C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for F21C. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500											-3.698	Likely Benign	0.686	Likely Pathogenic	Likely Benign										0.151	Likely Benign	-0.31	Neutral	0.880	Possibly Damaging	0.759	Possibly Damaging	4.12	Benign	0.00	Affected			0.2873	0.2171		-4	-2	-0.3	-44.04
c.653T>G	F218C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218C is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33435295‑T‑G). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools (REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. Results that are uncertain or unavailable are FoldX, ESM1b, AlphaMissense‑Optimized, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic prediction (2 pathogenic vs. 1 benign votes); and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F218C, 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.		PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000								6-33435295-T-G	1	6.20e-7	-7.234	In-Between	0.948	Likely Pathogenic	Ambiguous	1.49	Ambiguous	0.1	2.20	Destabilizing	1.85	Ambiguous	1.02	Destabilizing	0.744	Likely Pathogenic	-4.92	Deleterious	0.994	Probably Damaging	0.667	Possibly Damaging	5.78	Benign	0.03	Affected	3.41	13	0.2330	0.1321		-2	-4	-0.3	-44.04
c.659T>G	F220C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F220C is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM. 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 it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, 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	PH	0.219301	Structured	0.429422	Uncertain	0.898	0.295	0.000											-12.948	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	3.67	Destabilizing	0.0	5.03	Destabilizing	4.35	Destabilizing	2.22	Destabilizing	0.941	Likely Pathogenic	-6.72	Deleterious	0.994	Probably Damaging	0.753	Possibly Damaging	4.03	Benign	0.00	Affected			0.2264	0.2012		-4	-2	-0.3	-44.04
c.692T>G	F231C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231C is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a deleterious effect, while only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce the pathogenic signal: 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. Based on the overwhelming agreement among the majority of tools and the high‑accuracy methods, 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	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000											-13.315	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.26	Destabilizing	0.3	2.82	Destabilizing	2.54	Destabilizing	2.04	Destabilizing	0.937	Likely Pathogenic	-6.89	Deleterious	0.992	Probably Damaging	0.707	Possibly Damaging	5.49	Benign	0.00	Affected			0.2527	0.1612		-4	-2	-0.3	-44.04
c.920T>G	F307C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F307C missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors overwhelmingly indicate a deleterious effect: all tools that provide a definitive call—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The only predictions that are inconclusive are FoldX, Rosetta, and Foldetta, which are treated as unavailable. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. **Based on the consensus of the available predictions, the variant is most likely pathogenic, and this assessment is not contradicted by any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-11.484	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.1	1.44	Ambiguous	1.40	Ambiguous	1.05	Destabilizing	0.754	Likely Pathogenic	-7.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.2729	0.1628		-4	-2	-0.3	-44.04
c.935T>G	F312C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312C is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Based on the unanimous pathogenic predictions and the absence of benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-11.991	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.98	Destabilizing	0.3	4.97	Destabilizing	3.98	Destabilizing	1.46	Destabilizing	0.870	Likely Pathogenic	-7.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.16	Pathogenic	0.00	Affected			0.2293	0.2010		-4	-2	-0.3	-44.04
c.941T>G	F314C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. All available evidence points to a damaging effect. Consequently, 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	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-12.458	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	3.37	Destabilizing	0.3	2.64	Destabilizing	3.01	Destabilizing	2.49	Destabilizing	0.674	Likely Pathogenic	-6.89	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.13	Pathogenic	0.00	Affected			0.2401	0.1075		-4	-2	-0.3	-44.04
c.1013A>C	D338A 2D 3DClick to see structure in 3D Viewer AISynGAP1 D338A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, polyPhen‑2 HumVar, and SIFT, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-10.639	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	1.22	Ambiguous	0.3	1.11	Ambiguous	1.17	Ambiguous	0.16	Likely Benign	0.479	Likely Benign	-5.74	Deleterious	0.625	Possibly Damaging	0.192	Benign	1.73	Pathogenic	0.11	Tolerated			0.3830	0.5988		0	-2	5.3	-44.01
c.119A>C	D40A 2D AIThe SynGAP1 missense variant D40A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are not available. Taken together, the majority of evidence supports a benign interpretation, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-3.630	Likely Benign	0.339	Likely Benign	Likely Benign										0.122	Likely Benign	-1.22	Neutral	0.006	Benign	0.023	Benign	4.05	Benign	0.00	Affected			0.4299	0.7993		0	-2	5.3	-44.01
c.1388A>C	D463A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely pathogenic, and Foldetta predicts a benign effect on protein stability. Overall, the majority of tools and the consensus high‑accuracy prediction lean toward pathogenicity, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-8.607	Likely Pathogenic	0.894	Likely Pathogenic	Ambiguous	-0.04	Likely Benign	0.1	0.96	Ambiguous	0.46	Likely Benign	0.43	Likely Benign	0.425	Likely Benign	-6.96	Deleterious	0.978	Probably Damaging	0.602	Possibly Damaging	3.33	Benign	0.29	Tolerated			0.3591	0.5169		0	-2	5.3	-44.01
c.1400A>C	D467A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D467A 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 premPS and SIFT, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results—FoldX, Rosetta, and Foldetta—do not provide decisive evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-12.499	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.1	0.79	Ambiguous	0.81	Ambiguous	0.23	Likely Benign	0.790	Likely Pathogenic	-7.71	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.19	Pathogenic	0.07	Tolerated			0.3134	0.5117		0	-2	5.3	-44.01
c.1421A>C	D474A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, SGM Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-11.082	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.08	Likely Benign	0.0	0.15	Likely Benign	0.12	Likely Benign	0.17	Likely Benign	0.757	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.22	Pathogenic	0.22	Tolerated			0.3265	0.4354		0	-2	5.3	-44.01
c.1523A>C	D508A 2D 3DClick to see structure in 3D Viewer AISynGAP1 D508A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give a split result: AlphaMissense‑Optimized predicts benign, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain. No prediction or stability result is missing; all available outputs are considered. Overall, the predictions are evenly divided between benign and pathogenic, with no clear consensus. Therefore, the variant is inconclusive; it is not contradictory to the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-11.434	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	-0.18	Likely Benign	0.2	1.84	Ambiguous	0.83	Ambiguous	0.09	Likely Benign	0.339	Likely Benign	-7.37	Deleterious	0.988	Probably Damaging	0.762	Possibly Damaging	3.37	Benign	0.06	Tolerated			0.3758	0.4241		0	-2	5.3	-44.01
c.1580A>C	D527A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS, while the remaining evaluated methods (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict pathogenicity. FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-15.473	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.9	1.75	Ambiguous	1.28	Ambiguous	-0.24	Likely Benign	0.929	Likely Pathogenic	-7.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-2.39	Pathogenic	0.00	Affected			0.2850	0.3799		0	-2	5.3	-44.01
c.1748A>C	D583A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D583A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, SIFT, and ESM1b, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain and thus not counted. High‑accuracy methods give AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (10 pathogenic vs. 5 benign) and the two high‑accuracy pathogenic calls outweigh the single high‑accuracy benign call, indicating that the variant is most likely pathogenic. 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	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-4.545	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.2	-0.16	Likely Benign	0.41	Likely Benign	0.13	Likely Benign	0.787	Likely Pathogenic	-7.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.39	Pathogenic	0.14	Tolerated			0.3025	0.3705		0	-2	5.3	-44.01
c.1757A>C	D586A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D586A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include FoldX, SIFT, and premPS, whereas a majority of predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains inconclusive. No evidence from the uncertain tools (Rosetta, Foldetta) alters this consensus. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-9.955	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.41	Likely Benign	0.2	0.88	Ambiguous	0.65	Ambiguous	0.25	Likely Benign	0.693	Likely Pathogenic	-4.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.22	Pathogenic	0.31	Tolerated			0.3397	0.4673		0	-2	5.3	-44.01
c.179A>C	D60A 2D AIThe SynGAP1 D60A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evaluated tools lean toward a benign interpretation, with no evidence of pathogenicity from the high‑confidence methods. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as none exists for this allele. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-4.500	Likely Benign	0.918	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-2.17	Neutral	0.909	Possibly Damaging	0.857	Possibly Damaging	3.96	Benign	0.00	Affected			0.3851	0.7405		0	-2	5.3	-44.01
c.1847A>C	D616A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616A missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, and polyPhen‑2 HumVar, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), Rosetta, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as benign, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-11.386	Likely Pathogenic	0.664	Likely Pathogenic	Likely Benign	1.76	Ambiguous	0.2	2.07	Destabilizing	1.92	Ambiguous	0.41	Likely Benign	0.126	Likely Benign	-6.13	Deleterious	0.539	Possibly Damaging	0.122	Benign	3.32	Benign	0.10	Tolerated			0.3543	0.4207		0	-2	5.3	-44.01
c.185A>C	D62A 2D AIThe SynGAP1 D62A missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.476010	Uncertain	0.575	0.720	0.125											-3.983	Likely Benign	0.318	Likely Benign	Likely Benign										0.070	Likely Benign	-1.67	Neutral	0.006	Benign	0.023	Benign	4.09	Benign	0.00	Affected			0.4152	0.5972		0	-2	5.3	-44.01
c.1931A>C	D644A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D644A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, Foldetta, and premPS. Only PROVEAN predicts it as pathogenic, while Rosetta and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign; and Foldetta also predicts benign stability. Based on the aggregate evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000											-3.358	Likely Benign	0.502	Ambiguous	Likely Benign	-0.14	Likely Benign	0.1	-0.83	Ambiguous	-0.49	Likely Benign	-0.18	Likely Benign	0.274	Likely Benign	-3.90	Deleterious	0.311	Benign	0.032	Benign	3.51	Benign	0.39	Tolerated			0.3883	0.5481		0	-2	5.3	-44.01
c.2012A>C	D671A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671A missense variant is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic interpretation, with seven tools supporting pathogenicity versus four supporting benignity. This conclusion does not conflict with ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-11.709	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	0.25	Likely Benign	0.1	0.79	Ambiguous	0.52	Ambiguous	0.10	Likely Benign	0.245	Likely Benign	-5.08	Deleterious	0.980	Probably Damaging	0.804	Possibly Damaging	3.34	Benign	0.03	Affected			0.4056	0.5895		0	-2	5.3	-44.01
c.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.212A>C	D71A 2D AIThe SynGAP1 D71A missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this 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 Benign		0.575842	Disordered	0.456046	Uncertain	0.350	0.799	0.375											-3.422	Likely Benign	0.619	Likely Pathogenic	Likely Benign										0.077	Likely Benign	-1.89	Neutral	0.092	Benign	0.011	Benign	4.06	Benign	0.00	Affected			0.3876	0.6040		0	-2	5.3	-44.01
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.2285A>C	D762A 2D AIThe SynGAP1 D762A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool yields an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward a pathogenic impact. This assessment does not contradict any ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-4.510	Likely Benign	0.912	Likely Pathogenic	Ambiguous										0.178	Likely Benign	-2.40	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	2.12	Pathogenic	0.05	Affected			0.4632	0.8428		0	-2	5.3	-44.01
c.2303A>C	D768A 2D AIThe SynGAP1 D768A variant is listed in gnomAD (ID 6‑33442461‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic predictions (ESM1b, AlphaMissense‑Default). AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and thus unavailable; Foldetta stability analysis is not reported. Overall, the preponderance of evidence (six benign vs two pathogenic) points to a benign effect. 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.			0.332115	Structured	0.928237	Binding	0.314	0.877	0.250								6-33442461-A-C			-8.153	Likely Pathogenic	0.786	Likely Pathogenic	Ambiguous										0.174	Likely Benign	-1.84	Neutral	0.245	Benign	0.096	Benign	4.09	Benign	0.14	Tolerated	3.64	6	0.3924	0.7662		-2	0	5.3	-44.01
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.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.2477A>C	D826A 2D AIThe SynGAP1 D826A missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.627309	Binding	0.327	0.886	0.625											-5.590	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic										0.307	Likely Benign	-3.77	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.53	Benign	0.02	Affected			0.4463	0.7867		0	-2	5.3	-44.01
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.2546A>C	D849A 2D AIThe SynGAP1 missense variant D849A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, 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 Benign		0.712013	Disordered	0.554191	Binding	0.319	0.813	0.500											-2.843	Likely Benign	0.193	Likely Benign	Likely Benign										0.163	Likely Benign	-0.83	Neutral	0.611	Possibly Damaging	0.239	Benign	4.25	Benign	0.00	Affected			0.4618	0.7799		0	-2	5.3	-44.01
c.2603A>C	D868A 2D AIThe SynGAP1 D868A variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the balance of evidence—including the benign prediction from the most accurate AlphaMissense‑Optimized model and the majority of benign calls—suggests that the variant is most likely benign. This conclusion does not contradict any ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-2.764	Likely Benign	0.702	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-2.75	Deleterious	0.972	Probably Damaging	0.760	Possibly Damaging	2.54	Benign	0.21	Tolerated			0.4590	0.6990		0	-2	5.3	-44.01
c.2741A>C	D914A 2D AIThe SynGAP1 missense variant D914A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for D914A, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250											-1.690	Likely Benign	0.387	Ambiguous	Likely Benign										0.128	Likely Benign	-1.48	Neutral	0.996	Probably Damaging	0.953	Probably Damaging	2.69	Benign	0.05	Affected			0.4413	0.7086		0	-2	5.3	-44.01
c.2810A>C	D937A 2D AIThe SynGAP1 missense variant D937A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, 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 Benign		0.819762	Disordered	0.963385	Binding	0.348	0.883	0.625											-1.652	Likely Benign	0.385	Ambiguous	Likely Benign										0.096	Likely Benign	-1.45	Neutral	0.995	Probably Damaging	0.895	Possibly Damaging	2.76	Benign	0.10	Tolerated			0.4296	0.7244		0	-2	5.3	-44.01
c.2921A>C	D974A 2D AIThe SynGAP1 missense variant D974A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that D974A is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.964377	Binding	0.389	0.897	0.625											-2.619	Likely Benign	0.224	Likely Benign	Likely Benign										0.242	Likely Benign	-0.96	Neutral	0.001	Benign	0.002	Benign	4.22	Benign	0.04	Affected			0.3398	0.7129		0	-2	5.3	-44.01
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.3023A>C	D1008A 2D AIThe SynGAP1 D1008A variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and no ClinVar evidence contradicts this assessment. 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.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625											-3.210	Likely Benign	0.861	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-2.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			0.4014	0.6444		0	-2	5.3	-44.01
c.3047A>C	D1016A 2D AIThe SynGAP1 D1016A variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus leave the functional impact uncertain. **Based on the current predictions, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which has no entry for this variant.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-2.120	Likely Benign	0.637	Likely Pathogenic	Likely Benign										0.248	Likely Benign	-2.71	Deleterious	0.856	Possibly Damaging	0.492	Possibly Damaging	2.50	Benign	0.02	Affected			0.4040	0.6760		0	-2	5.3	-44.01
c.3077A>C	D1026A 2D AIThe SynGAP1 D1026A variant is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a tie, and Foldetta results are not available. Overall, the majority of standard tools favor a benign interpretation, and no ClinVar entry contradicts this assessment. Thus, the variant is most likely benign based on current predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500											-4.211	Likely Benign	0.849	Likely Pathogenic	Ambiguous										0.070	Likely Benign	-2.69	Deleterious	0.112	Benign	0.061	Benign	2.53	Benign	0.02	Affected			0.3392	0.5279		0	-2	5.3	-44.01
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.3563A>C	D1188A 2D AIThe SynGAP1 D1188A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This prediction is consistent with the lack of ClinVar annotation and gnomAD presence, indicating no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-4.369	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.439	Likely Benign	-3.91	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	5.45	Benign	0.00	Affected			0.2768	0.4495		0	-2	5.3	-44.01
c.3578A>C	D1193A 2D AIThe SynGAP1 missense variant D1193A is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Based on the majority of predictions and the consensus from high‑accuracy tools, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375											-5.747	Likely Benign	0.767	Likely Pathogenic	Likely Benign										0.486	Likely Benign	-2.42	Neutral	0.856	Possibly Damaging	0.492	Possibly Damaging	5.48	Benign	0.00	Affected			0.2719	0.4017		0	-2	5.3	-44.01
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.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.3878A>C	D1293A 2D AIThe SynGAP1 missense variant D1293A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence (5 benign vs 4 pathogenic predictions) leans toward a benign classification. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.892346	Binding	0.569	0.801	0.625											-2.251	Likely Benign	0.197	Likely Benign	Likely Benign										0.302	Likely Benign	-5.19	Deleterious	0.770	Possibly Damaging	0.255	Benign	2.20	Pathogenic	0.00	Affected			0.3267	0.3447		0	-2	5.3	-44.01
c.4025A>C	D1342A 2D AIThe SynGAP1 missense variant D1342A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for D1342A, 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 Benign		0.921076	Disordered	0.981682	Binding	0.316	0.678	0.875											-2.719	Likely Benign	0.145	Likely Benign	Likely Benign										0.049	Likely Benign	-0.58	Neutral	0.371	Benign	0.084	Benign	4.06	Benign	0.02	Affected			0.4270	0.5676		0	-2	5.3	-44.01
c.452A>C	D151A 2D AIThe SynGAP1 D151A missense variant is listed in gnomAD (ID 6‑33432749‑A‑C) but has no ClinVar entry. Functional prediction tools fall into two groups: benign predictions come from 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 pathogenicity. High‑accuracy assessments further support a deleterious effect: 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 majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625								6-33432749-A-C	1	6.21e-7	-9.693	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.326	Likely Benign	-4.51	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.91	Benign	0.01	Affected	3.61	5	0.4286	0.7424		-2	0	5.3	-44.01
c.500A>C	D167A 2D AIThe SynGAP1 D167A missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools split evenly: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, 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 predictor, has no available result for this residue. Taken together, the preponderance of evidence, especially the SGM Consensus, points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-13.473	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.61	Deleterious	0.141	Benign	0.056	Benign	3.97	Benign	0.00	Affected			0.3429	0.6549		0	-2	5.3	-44.01
c.506A>C	D169A 2D AIThe SynGAP1 D169A missense variant is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, the benign set includes REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; the pathogenic set includes PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta predictions are unavailable. Overall, the balance of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125											-11.065	Likely Pathogenic	0.874	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-3.15	Deleterious	0.018	Benign	0.025	Benign	4.10	Benign	0.01	Affected			0.4012	0.6809		0	-2	5.3	-44.01
c.602A>C	D201A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D201A variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM, whereas a pathogenic consensus is reached by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or unavailable results come from Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward pathogenic, and Foldetta remains inconclusive. Overall, the majority of standard tools favor a benign classification, but the high‑accuracy consensus indicates a pathogenic signal, leaving the variant’s impact uncertain. The predictions do 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.		PH	0.366687	Structured	0.428570	Uncertain	0.698	0.447	0.125											-7.793	In-Between	0.769	Likely Pathogenic	Likely Benign	0.45	Likely Benign	0.1	1.86	Ambiguous	1.16	Ambiguous	0.23	Likely Benign	0.261	Likely Benign	-3.81	Deleterious	0.989	Probably Damaging	0.828	Possibly Damaging	4.11	Benign	0.09	Tolerated			0.3177	0.5050		0	-2	5.3	-44.01
c.608A>C	D203A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. All available predictions and stability analyses point to a benign impact. Therefore, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-6.807	Likely Benign	0.373	Ambiguous	Likely Benign	0.07	Likely Benign	0.1	0.49	Likely Benign	0.28	Likely Benign	0.12	Likely Benign	0.174	Likely Benign	-3.34	Deleterious	0.941	Possibly Damaging	0.607	Possibly Damaging	4.05	Benign	0.17	Tolerated			0.2527	0.4128		0	-2	5.3	-44.01
c.68A>C	D23A 2D AIThe SynGAP1 D23A missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic versus four benign) suggest a pathogenic impact. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.557691	Disordered	0.440341	Uncertain	0.369	0.892	0.375											-2.732	Likely Benign	0.777	Likely Pathogenic	Likely Benign										0.112	Likely Benign	-2.57	Deleterious	0.909	Possibly Damaging	0.539	Possibly Damaging	3.52	Benign	0.00	Affected			0.4613	0.8203		0	-2	5.3	-44.01
c.719A>C	D240A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D240A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are premPS and FATHMM, while the remaining pathogenic‑predicting tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently flag the variant as deleterious. Tools with uncertain outcomes (FoldX, Rosetta, Foldetta) provide no definitive guidance. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta remains inconclusive. Overall, the preponderance 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	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000											-12.935	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.75	Ambiguous	0.1	0.99	Ambiguous	0.87	Ambiguous	0.22	Likely Benign	0.872	Likely Pathogenic	-7.03	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	5.80	Benign	0.05	Affected			0.3317	0.4992		0	-2	5.3	-44.01
c.764A>C	D255A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D255A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, while the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Pathogenic” vote) predict a pathogenic impact. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore do not contribute evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250											-11.789	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.48	Ambiguous	0.2	1.04	Ambiguous	1.26	Ambiguous	0.35	Likely Benign	0.829	Likely Pathogenic	-6.85	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	5.80	Benign	0.01	Affected			0.3363	0.4805		0	-2	5.3	-44.01
c.782A>C	D261A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D261A missense variant is not reported in ClinVar (status: None) and has no entries in gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, while the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Given the preponderance of pathogenic predictions and the lack of conflicting evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-11.426	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	1.70	Ambiguous	0.3	1.46	Ambiguous	1.58	Ambiguous	0.04	Likely Benign	0.839	Likely Pathogenic	-4.59	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	5.80	Benign	0.04	Affected			0.2785	0.4577		0	-2	5.3	-44.01
c.860A>C	D287A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D287A is listed in ClinVar with an Uncertain significance status and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, FoldX, Rosetta, Foldetta, and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta) as benign. The overall tally favors pathogenicity (8 tools vs 5 benign), but the conflicting high‑accuracy results leave uncertainty. Thus, the variant is most likely pathogenic according to the majority of predictions, which does not contradict its ClinVar Uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000					Uncertain		1				-14.686	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	-0.04	Likely Benign	0.13	Likely Benign	0.40	Likely Benign	0.484	Likely Benign	-7.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.58	Pathogenic	0.01	Affected	3.38	23	0.4448	0.7431		-2	0	5.3	-44.01
c.863A>C	D288A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and SIFT. Those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized, Foldetta, and Rosetta give uncertain results and are treated as unavailable for pathogenicity inference. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain. Overall, seven tools predict pathogenicity while four predict benign, with no conflicting ClinVar evidence. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-13.470	Likely Pathogenic	0.908	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	1.27	Ambiguous	0.81	Ambiguous	0.10	Likely Benign	0.451	Likely Benign	-6.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.71	Pathogenic	0.07	Tolerated			0.4060	0.5788		0	-2	5.3	-44.01
c.911A>C	D304A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304A variant has no ClinVar entry and is not listed in gnomAD. Prediction tools that classify it as benign include premPS, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) all predict a pathogenic effect. 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 uncertain. Overall, the majority of evidence points to a pathogenic impact. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-6.258	Likely Benign	0.604	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.1	0.54	Ambiguous	0.77	Ambiguous	0.39	Likely Benign	0.523	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.80	Pathogenic	0.02	Affected			0.4457	0.6642		0	-2	5.3	-44.01
c.989A>C	D330A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D330A 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 SIFT, while a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—do not provide definitive evidence. High‑accuracy methods give the following: SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; AlphaMissense‑Optimized is uncertain; Foldetta is also uncertain. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for D330A. This conclusion is not contradicted by ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250											-14.051	Likely Pathogenic	0.929	Likely Pathogenic	Ambiguous	1.75	Ambiguous	0.3	1.06	Ambiguous	1.41	Ambiguous	0.60	Ambiguous	0.399	Likely Benign	-5.49	Deleterious	0.961	Probably Damaging	0.655	Possibly Damaging	0.93	Pathogenic	0.11	Tolerated			0.4087	0.4476		0	-2	5.3	-44.01
c.995A>C	D332A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D332A 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 Rosetta, while 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 of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain or inconclusive results come from FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion 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	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-12.290	Likely Pathogenic	0.876	Likely Pathogenic	Ambiguous	1.19	Ambiguous	0.2	0.32	Likely Benign	0.76	Ambiguous	0.54	Ambiguous	0.458	Likely Benign	-6.45	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.24	Pathogenic	0.02	Affected			0.2998	0.4176		0	-2	5.3	-44.01
c.1004G>T	R335L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335L is not listed in ClinVar (ClinVar ID None) and has no reported allele in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX are uncertain and are treated as unavailable for pathogenicity inference. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-13.226	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.0	-0.19	Likely Benign	0.16	Likely Benign	0.40	Likely Benign	0.196	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.73	Pathogenic	0.04	Affected			0.1382	0.4753		-3	-2	8.3	-43.03
c.1067G>T	R356L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R356L is not reported in ClinVar and is present in gnomAD (ID 6‑33437972‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, FoldX, and Foldetta, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for R356L, and this conclusion does not contradict ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250								6-33437972-G-T			-13.957	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	-0.04	Likely Benign	0.1	-0.57	Ambiguous	-0.31	Likely Benign	0.68	Ambiguous	0.412	Likely Benign	-6.20	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	1.69	Pathogenic	0.02	Affected	3.39	22	0.2110	0.5242		-2	-3	8.3	-43.03
c.1202G>T	R401L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401L is not reported in ClinVar and is present in gnomAD (ID 6‑33438107‑G‑T). Prediction tools that classify the variant as benign include Rosetta, FATHMM, and premPS, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX alone is available. Based on the preponderance of pathogenic predictions and the corroborating high‑accuracy tools, R401L 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	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000								6-33438107-G-T	1	6.20e-7	-12.280	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	-1.52	Ambiguous	0.1	-0.23	Likely Benign	-0.88	Ambiguous	0.22	Likely Benign	0.858	Likely Pathogenic	-6.42	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	5.44	Benign	0.02	Affected	3.38	27	0.1972	0.4263		-2	-3	8.3	-43.03
c.1214G>T	R405L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R405L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect 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) indicate a pathogenic or likely pathogenic impact. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta providing an inconclusive stability prediction. Overall, the preponderance of evidence points to a pathogenic effect for R405L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.576	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.43	Ambiguous	0.7	0.40	Likely Benign	0.92	Ambiguous	0.72	Ambiguous	0.512	Likely Pathogenic	-6.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.64	Benign	0.01	Affected			0.2126	0.5555		-3	-2	8.3	-43.03
c.122G>T	R41L 2D AIThe SynGAP1 missense variant R41L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for R41L, 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 Benign		0.311707	Structured	0.431757	Uncertain	0.344	0.765	0.375											-3.173	Likely Benign	0.261	Likely Benign	Likely Benign										0.111	Likely Benign	-0.58	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	4.18	Benign	0.00	Affected			0.2134	0.5868		-3	-2	8.3	-43.03
c.1286G>T	R429L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. No contradictory evidence is present from ClinVar or gnomAD. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000											-6.495	Likely Benign	0.408	Ambiguous	Likely Benign	-0.05	Likely Benign	0.1	0.06	Likely Benign	0.01	Likely Benign	-0.12	Likely Benign	0.241	Likely Benign	-1.20	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.59	Benign	0.37	Tolerated			0.1555	0.4025		-3	-2	8.3	-43.03
c.140G>T	R47L 2D AIThe SynGAP1 missense variant R47L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R47L. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125											-5.758	Likely Benign	0.664	Likely Pathogenic	Likely Benign										0.130	Likely Benign	-1.76	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	4.04	Benign	0.00	Affected			0.1904	0.5206		-3	-2	8.3	-43.03
c.1424G>T	R475L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R475L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, whereas only Rosetta predicts a benign outcome. 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 uncertain. With the preponderance of pathogenic calls and no conflicting evidence from ClinVar or population databases, 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	GAP	0.175930	Structured	0.382696	Uncertain	0.852	0.261	0.000											-13.074	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	1.49	Ambiguous	0.4	-0.47	Likely Benign	0.51	Ambiguous	0.55	Ambiguous	0.806	Likely Pathogenic	-6.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.40	Pathogenic	0.00	Affected			0.1580	0.3428		-3	-2	8.3	-43.03
c.1436G>T	R479L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R479L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). AlphaMissense‑Optimized is uncertain. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized remains uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No single metric dominates, and the overall evidence is balanced. Therefore, the variant’s pathogenicity is inconclusive; it is not contradicted by ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000											-11.118	Likely Pathogenic	0.832	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.12	Likely Benign	0.29	Likely Benign	0.39	Likely Benign	0.265	Likely Benign	-4.21	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.38	Benign	0.15	Tolerated			0.1326	0.3624		-3	-2	8.3	-43.03
c.1454G>T	R485L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R485L is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the 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	GAP	0.188120	Structured	0.377409	Uncertain	0.805	0.246	0.125											-15.807	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.23	Likely Benign	0.2	0.14	Likely Benign	0.19	Likely Benign	0.39	Likely Benign	0.631	Likely Pathogenic	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.92	Pathogenic	0.00	Affected			0.1715	0.3784		-3	-2	8.3	-43.03
c.1496G>T	R499I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R499I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely pathogenic. No tool predicts a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are uncertain or inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the overwhelming majority of evidence supports a pathogenic effect, and this is consistent with the absence of a ClinVar entry; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.071867	Structured	0.386723	Uncertain	0.899	0.146	0.000											-9.069	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	1.53	Ambiguous	0.1	0.61	Ambiguous	1.07	Ambiguous	0.57	Ambiguous	0.713	Likely Pathogenic	-5.50	Deleterious	0.998	Probably Damaging	0.922	Probably Damaging	-1.47	Pathogenic	0.00	Affected			0.1401	0.2146		-2	-3	9.0	-43.03
c.14G>T	R5L 2D AIThe SynGAP1 missense variant R5L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.547847	Binding	0.363	0.920	0.750											-3.297	Likely Benign	0.274	Likely Benign	Likely Benign										0.158	Likely Benign	-0.06	Neutral	0.030	Benign	0.003	Benign	4.14	Benign	0.00	Affected			0.2256	0.5914		-3	-2	8.3	-43.03
c.1544G>T	R515L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R515L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome; FoldX and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.055536	Structured	0.191256	Uncertain	0.924	0.275	0.000											-10.738	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign	0.71	Ambiguous	0.2	-0.33	Likely Benign	0.19	Likely Benign	0.52	Ambiguous	0.686	Likely Pathogenic	-4.53	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.26	Pathogenic	0.11	Tolerated			0.1666	0.2857		-3	-2	8.3	-43.03
c.1631G>T	R544L 2D AIThe SynGAP1 R544L missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the predictions are mixed, with a slight majority leaning toward pathogenicity, and there is no ClinVar entry to contradict these findings. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038858	Structured	0.016004	Uncertain	0.967	0.333	0.000											-13.159	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	-0.34	Likely Benign	0.6	0.08	Likely Benign	-0.13	Likely Benign	0.29	Likely Benign	0.573	Likely Pathogenic	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.42	Pathogenic	0.24	Tolerated			0.1478	0.3191		-3	-2	8.3	-43.03
c.1718G>T	R573L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R573L is listed in ClinVar as Pathogenic (ClinVar ID 521291.0) and is not reported in gnomAD. Functional prediction tools that assess sequence conservation and structural impact uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic. No tool in the dataset predicts a benign outcome. Predictions that rely on protein‑folding stability (FoldX, Rosetta, Foldetta, premPS) are inconclusive and are therefore treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports pathogenic; Foldetta remains uncertain. Based on the collective evidence, the variant is most likely pathogenic, which is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.032433	Uncertain	0.934	0.235	0.000					Likely Pathogenic		1				-13.120	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.30	Ambiguous	0.6	1.11	Ambiguous	1.21	Ambiguous	0.80	Ambiguous	0.833	Likely Pathogenic	-5.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.41	Pathogenic	0.01	Affected	3.37	35	0.1503	0.3083		-3	-2	8.3	-43.03	237.4	60.7	0.0	0.0	-0.7	0.3	X	X						Potentially Pathogenic	The guanidinium group of Arg573, located in an α-helix (res. Arg563-Glu578), forms a salt bridge with the carboxylate groups of Glu582 and/or Asp586 from a nearby α-helix (res. Glu582-Met603) in the WT simulations. Additionally, the Arg573 side chain stacks planarly with the aromatic phenol ring of Tyr665 and hydrogen bonds with the hydroxyl group of Ser668 from another α-helix (res. Ser641-Ser668). In the variant simulations, the aliphatic iso-butyl group of the Leu573 side chain fails to establish any of these interactions, which, in turn, lowers the integrity of the opposing α-helix end (res. Glu582-Met603). Overall, the residue swap has the potential to substantially affect the tertiary structure assembly during the protein folding process.	10.1016/j.ajhg.2020.11.011
c.1724G>T	R575L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R575L 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 SIFT, FoldX, and Foldetta. Those that predict pathogenicity comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Benign. Overall, the majority of tools (10/13) predict pathogenicity, and the high‑accuracy consensus leans toward pathogenic, though Foldetta suggests stability‑preserving benign effects. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000											-12.442	Likely Pathogenic	0.788	Likely Pathogenic	Ambiguous	-0.04	Likely Benign	0.1	-0.89	Ambiguous	-0.47	Likely Benign	0.59	Ambiguous	0.602	Likely Pathogenic	-4.42	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated			0.1574	0.2991		-3	-2	8.3	-43.03
c.1736G>T	R579L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R579L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas those that predict a pathogenic impact are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) 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) as benign. Overall, the majority of evidence (seven pathogenic vs. five benign predictions) points to a pathogenic effect for R579L. 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	0.053060	Structured	0.022872	Uncertain	0.877	0.244	0.000											-9.290	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	-0.24	Likely Benign	0.1	0.07	Likely Benign	-0.09	Likely Benign	0.48	Likely Benign	0.802	Likely Pathogenic	-6.39	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.36	Pathogenic	0.06	Tolerated			0.1747	0.3259		-3	-2	8.3	-43.03
c.1742G>T	R581L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R581L is not reported in ClinVar and is present in gnomAD (ID 6‑33440794‑G‑T). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas tools that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. In contrast, the Foldetta stability assessment, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of computational evidence supports a pathogenic classification for R581L, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.029544	Uncertain	0.829	0.236	0.000								6-33440794-G-T	3	1.86e-6	-10.134	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.1	-0.20	Likely Benign	0.05	Likely Benign	0.45	Likely Benign	0.654	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.33	Pathogenic	0.08	Tolerated	3.37	34	0.1550	0.3483		-2	-3	8.3	-43.03
c.1787G>T	R596L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R596L missense variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect are Foldetta and premPS, whereas the remaining pathogenic‑predicting tools—REVEL, 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 indicate a deleterious impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (derived from the same four high‑confidence predictors) also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the preponderance of evidence points to a pathogenic effect for R596L, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.017797	Structured	0.135423	Uncertain	0.918	0.134	0.000					Uncertain		1				-13.197	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.51	Ambiguous	0.3	-0.58	Ambiguous	0.47	Likely Benign	-0.02	Likely Benign	0.756	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.45	Pathogenic	0.00	Affected	3.37	35	0.1755	0.3433		-3	-2	8.3	-43.03	234.2	63.4	-0.1	0.0	-0.5	0.6		X		X				Potentially Pathogenic	The guanidinium group of Arg596, located in an α helix (res. Glu582-Met603), forms a salt bridge with the carboxylate group of Glu495 from another α helix (res. Leu489-Glu519). In the WT simulations, the side chain of Arg596 hydrogen bonds with the backbone carbonyl groups of Asn487, Glu486, Arg485, and Phe484. Additionally, Arg596 can hydrogen bond with the carboxamide group of the Asn487 side chain on an opposing loop that links two α helices (res. Ala461-Arg475, res. Leu489-Glu519).However, in the variant simulations, the branched hydrocarbon side chain of Leu596 cannot form any of the hydrogen bonds or salt bridges maintained by the considerably bulkier and positively charged Arg596 side chain. Instead, Leu596 packs hydrophobically with the phenyl ring of Phe484 in the linker loop or residues from the opposing helix (e.g., Ile494, Thr491).Thus, the residue swap could affect the tertiary structure assembly more profoundly than observed in the simulations. Notably, Arg596 plays a key role in positioning the aforementioned loop, which is crucial for the placement of the “arginine finger” or the Arg485 side chain during RasGTPase activation.	10.1016/j.ajhg.2020.11.011
c.1862G>T	R621L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R621L has no ClinVar entry and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and FATHMM, whereas the majority—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—label it pathogenic or likely pathogenic. FoldX and Foldetta return uncertain results and are not considered evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, and Foldetta remains inconclusive. Overall, the consensus of the available predictions points to a pathogenic effect for R621L, 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	0.222385	Structured	0.084420	Uncertain	0.945	0.216	0.000											-16.055	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	1.70	Ambiguous	0.3	-0.22	Likely Benign	0.74	Ambiguous	0.34	Likely Benign	0.718	Likely Pathogenic	-6.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.83	Benign	0.00	Affected			0.1424	0.3568		-3	-2	8.3	-43.03
c.2060G>T	R687L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign include REVEL, SIFT, ESM1b, and FATHMM, while those that agree on pathogenic are AlphaMissense‑Default, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools—AlphaMissense‑Optimized, FoldX, Foldetta, and premPS—return uncertain or inconclusive results. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and Foldetta is uncertain. Consequently, the evidence does not strongly support either benign or pathogenic classification. The variant is therefore most likely inconclusive, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-6.925	Likely Benign	0.901	Likely Pathogenic	Ambiguous	1.43	Ambiguous	0.3	0.05	Likely Benign	0.74	Ambiguous	0.83	Ambiguous	0.448	Likely Benign	-5.76	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.90	Benign	0.10	Tolerated			0.1252	0.3376		-3	-2	8.3	-43.03
c.209G>T	R70L 2D AIThe SynGAP1 missense variant R70L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.458981	Uncertain	0.392	0.793	0.375											-3.422	Likely Benign	0.636	Likely Pathogenic	Likely Benign										0.125	Likely Benign	-1.39	Neutral	0.962	Probably Damaging	0.726	Possibly Damaging	4.11	Benign	0.00	Affected			0.1455	0.4554		-3	-2	8.3	-43.03
c.2147G>T	R716L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R716L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, premPS, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (7/13) lean toward pathogenicity, with a near‑even split and a slight edge for pathogenic. The variant is therefore most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists for R716L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000											-10.690	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign	0.31	Likely Benign	0.0	0.51	Ambiguous	0.41	Likely Benign	0.37	Likely Benign	0.289	Likely Benign	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.46	Benign	0.01	Affected			0.1701	0.3775		-3	-2	8.3	-43.03
c.215G>T	R72L 2D AIThe SynGAP1 missense variant R72L is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Pathogenicity is suggested only by polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for R72L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.455349	Uncertain	0.355	0.819	0.375											-3.102	Likely Benign	0.476	Ambiguous	Likely Benign										0.108	Likely Benign	-1.49	Neutral	0.686	Possibly Damaging	0.250	Benign	4.12	Benign	0.00	Affected			0.2104	0.4352		-3	-2	8.3	-43.03
c.2207G>T	R736L 2D AIThe SynGAP1 missense variant R736L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. 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 benign classification, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.415259	Uncertain	0.305	0.771	0.875											-4.173	Likely Benign	0.133	Likely Benign	Likely Benign										0.061	Likely Benign	-1.27	Neutral	0.653	Possibly Damaging	0.361	Benign	2.60	Benign	0.00	Affected			0.1856	0.3180		-3	-2	8.3	-43.03
c.2219G>T	R740L 2D AIThe SynGAP1 missense variant R740L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.475392	Uncertain	0.269	0.849	0.875											-4.958	Likely Benign	0.126	Likely Benign	Likely Benign										0.043	Likely Benign	-2.30	Neutral	0.064	Benign	0.040	Benign	2.57	Benign	0.03	Affected			0.2341	0.4243		-3	-2	8.3	-43.03
c.2225G>T	R742L 2D AIThe SynGAP1 missense variant R742L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.509587	Binding	0.309	0.856	0.875											-3.778	Likely Benign	0.101	Likely Benign	Likely Benign										0.064	Likely Benign	-0.77	Neutral	0.001	Benign	0.001	Benign	2.71	Benign	0.16	Tolerated			0.2342	0.3831		-3	-2	8.3	-43.03
c.2246G>T	R749L 2D AIThe SynGAP1 missense variant R749L is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy predictors that are available—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign classification. Consequently, the overall evidence points to the variant being most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.626050	Binding	0.337	0.860	0.625											-3.926	Likely Benign	0.413	Ambiguous	Likely Benign										0.168	Likely Benign	-2.15	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.65	Benign	0.01	Affected			0.2106	0.5154		-3	-2	8.3	-43.03
c.2282G>T	R761L 2D AIThe SynGAP1 missense variant R761L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact. This consensus does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250											-5.653	Likely Benign	0.718	Likely Pathogenic	Likely Benign										0.171	Likely Benign	-2.51	Deleterious	0.992	Probably Damaging	0.900	Possibly Damaging	2.70	Benign	0.24	Tolerated			0.1786	0.4326		-3	-2	8.3	-43.03
c.2324G>T	R775L 2D AIThe SynGAP1 missense variant R775L (ClinVar ID 4327035) is present in gnomAD (ID 6‑33442482‑G‑T). Prediction tools that agree on benign include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those predicting pathogenic are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also indicates likely benign; Foldetta results are unavailable. Overall, the consensus of computational evidence points to a benign effect, consistent with the ClinVar annotation and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.895337	Binding	0.320	0.896	0.250							1	6-33442482-G-T			-5.951	Likely Benign	0.598	Likely Pathogenic	Likely Benign										0.124	Likely Benign	-1.86	Neutral	0.933	Possibly Damaging	0.871	Possibly Damaging	4.13	Benign	0.06	Tolerated	3.64	6	0.1665	0.5089		-2	-3	8.3	-43.03
c.233G>T	R78L 2D AIThe SynGAP1 missense variant R78L is listed in ClinVar (ID 3390541.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, 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 Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500					Uncertain		1				-3.389	Likely Benign	0.635	Likely Pathogenic	Likely Benign										0.062	Likely Benign	-1.59	Neutral	0.385	Benign	0.021	Benign	3.84	Benign	0.00	Affected			0.1445	0.4276		-3	-2	8.3	-43.03
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.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.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.248G>T	R83I 2D AIThe SynGAP1 missense variant R83I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of evidence (seven pathogenic vs. three benign predictions) indicates that R83I is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.522784	Binding	0.275	0.895	0.250											-4.021	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-3.15	Deleterious	0.972	Probably Damaging	0.766	Possibly Damaging	3.17	Benign	0.00	Affected			0.1450	0.3219		-2	-3	9.0	-43.03
c.251G>T	R84L 2D AIThe SynGAP1 missense variant R84L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R84L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-7.579	In-Between	0.987	Likely Pathogenic	Likely Pathogenic										0.120	Likely Benign	-2.75	Deleterious	0.962	Probably Damaging	0.726	Possibly Damaging	3.70	Benign	0.00	Affected			0.1595	0.4653		-3	-2	8.3	-43.03
c.2561G>T	R854L 2D AIThe SynGAP1 missense variant R854L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for R854L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750											-2.573	Likely Benign	0.167	Likely Benign	Likely Benign										0.131	Likely Benign	-1.78	Neutral	0.960	Probably Damaging	0.765	Possibly Damaging	4.11	Benign	0.03	Affected			0.1875	0.5223		-3	-2	8.3	-43.03
c.2651G>T	R884L 2D AIThe SynGAP1 missense variant R884L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.641526	Binding	0.305	0.898	0.250											-3.482	Likely Benign	0.280	Likely Benign	Likely Benign										0.095	Likely Benign	-1.08	Neutral	0.300	Benign	0.191	Benign	2.63	Benign	0.24	Tolerated			0.1809	0.4177		-3	-2	8.3	-43.03
c.2669G>T	R890L 2D AIThe SynGAP1 missense variant R890L 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign prediction (2 benign vs. 1 pathogenic, with one 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‑accuracy and consensus predictions indicate a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625											-2.387	Likely Benign	0.389	Ambiguous	Likely Benign										0.213	Likely Benign	-2.74	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	3.98	Benign	0.20	Tolerated			0.1876	0.3406		-3	-2	8.3	-43.03
c.2714G>T	R905L 2D AIThe SynGAP1 missense variant R905L is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (allele ID 6‑33443266‑G‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of predictions leans toward a benign interpretation, and this conclusion does not contradict the ClinVar status, which currently has no assertion for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.618085	Binding	0.291	0.920	0.250								6-33443266-G-T			-3.284	Likely Benign	0.709	Likely Pathogenic	Likely Benign										0.242	Likely Benign	-2.55	Deleterious	0.963	Probably Damaging	0.753	Possibly Damaging	2.61	Benign	0.10	Tolerated	3.77	5	0.1676	0.4905		-2	-3	8.3	-43.03
c.2765G>T	R922L 2D AIThe SynGAP1 missense variant R922L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods that are available—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign interpretation. Therefore, the variant is most likely benign according to the consensus of predictive tools, 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 Benign		0.549308	Disordered	0.955308	Binding	0.277	0.845	0.375											-3.714	Likely Benign	0.546	Ambiguous	Likely Benign										0.150	Likely Benign	0.84	Neutral	0.983	Probably Damaging	0.828	Possibly Damaging	3.04	Benign	1.00	Tolerated			0.2033	0.5022		-3	-2	8.3	-43.03
c.278G>T	R93L 2D AIThe SynGAP1 R93L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.549151	Binding	0.290	0.874	0.625											-2.850	Likely Benign	0.425	Ambiguous	Likely Benign										0.064	Likely Benign	-1.72	Neutral	0.103	Benign	0.019	Benign	4.00	Benign	0.00	Affected			0.2197	0.4861		-3	-2	8.3	-43.03
c.2900G>T	R967L 2D AIThe SynGAP1 missense variant R967L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443452‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for R967L, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.974374	Disordered	0.969686	Binding	0.340	0.888	0.750					Uncertain		1	6-33443452-G-T	1	6.20e-7	-3.496	Likely Benign	0.164	Likely Benign	Likely Benign										0.123	Likely Benign	-0.99	Neutral	0.959	Probably Damaging	0.586	Possibly Damaging	4.15	Benign	0.75	Tolerated	4.32	2	0.1964	0.5093		-2	-3	8.3	-43.03
c.29G>T	R10L 2D AIThe SynGAP1 missense variant R10L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign impact, 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 Benign		0.534167	Disordered	0.513657	Binding	0.330	0.915	0.625											-3.269	Likely Benign	0.244	Likely Benign	Likely Benign										0.143	Likely Benign	0.09	Neutral	0.058	Benign	0.009	Benign	4.21	Benign	0.00	Affected			0.2255	0.5261		-3	-2	8.3	-43.03
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.3059G>T	R1020L 2D AISynGAP1 missense variant R1020L is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive; Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic effect, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500					Uncertain		1				-6.031	Likely Benign	0.907	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-4.03	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	2.50	Benign	0.00	Affected	3.77	5	0.1898	0.5214		-3	-2	8.3	-43.03
c.311G>T	R104L 2D AIThe SynGAP1 missense variant R104L is listed in ClinVar (ID 2746314.0) as Benign and is present in gnomAD (6‑33432176‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the ClinVar benign classification and does not contradict the existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.678998	Binding	0.339	0.869	0.625					Benign		1	6-33432176-G-T	1	6.20e-7	-3.563	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.170	Likely Benign	-1.38	Neutral	0.001	Benign	0.002	Benign	4.05	Benign	0.00	Affected	4.32	1	0.1681	0.4894		-2	-3	8.3	-43.03
c.3254G>T	R1085L 2D AIThe SynGAP1 missense variant R1085L is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R1085L, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000											-3.674	Likely Benign	0.734	Likely Pathogenic	Likely Benign										0.243	Likely Benign	-2.38	Neutral	0.997	Probably Damaging	0.993	Probably Damaging	2.72	Benign	0.01	Affected			0.1909	0.4568		-3	-2	8.3	-43.03
c.3308G>T	R1103L 2D AIThe SynGAP1 missense variant R1103L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443860‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this 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 Benign		0.945666	Disordered	0.957363	Binding	0.328	0.862	0.875					Uncertain		1	6-33443860-G-T			-2.330	Likely Benign	0.205	Likely Benign	Likely Benign										0.173	Likely Benign	-2.35	Neutral	0.002	Benign	0.005	Benign	2.44	Pathogenic	0.02	Affected	3.77	5	0.2098	0.5181		-3	-2	8.3	-43.03
c.3314G>T	R1105L 2D AIThe SynGAP1 missense variant R1105L is not reported in ClinVar and is present in gnomAD (ID 6‑33443866‑G‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments 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—labels it pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this residue, so its stability impact is unavailable. Overall, the balance of evidence leans toward a benign effect, with no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.901269	Disordered	0.954396	Binding	0.330	0.863	0.875								6-33443866-G-T			-4.031	Likely Benign	0.459	Ambiguous	Likely Benign										0.125	Likely Benign	-3.51	Deleterious	0.677	Possibly Damaging	0.168	Benign	2.46	Pathogenic	0.19	Tolerated	3.77	5	0.1734	0.5373		-2	-3	8.3	-43.03
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.3524G>T	R1175L 2D AISynGAP1 missense variant R1175L is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign predictions come from PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized is Uncertain, SGM‑Consensus remains Likely Benign, and Foldetta data are unavailable. Overall, the majority of individual predictors lean toward pathogenicity, yet the consensus of the most reliable tools suggests a benign outcome, leaving the variant’s clinical significance ambiguous. Consequently, the variant is most likely pathogenic based on the bulk of predictions, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.589347	Binding	0.545	0.732	0.375											-2.560	Likely Benign	0.876	Likely Pathogenic	Ambiguous										0.535	Likely Pathogenic	-2.37	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	5.38	Benign	0.00	Affected			0.1240	0.2849		-3	-2	8.3	-43.03
c.3572G>T	R1191L 2D AIThe SynGAP1 missense variant R1191L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1191L. This prediction 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.		Coiled-coil	0.661982	Disordered	0.439584	Uncertain	0.765	0.622	0.625											0.014	Likely Benign	0.981	Likely Pathogenic	Likely Pathogenic										0.352	Likely Benign	-2.82	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.64	Benign	0.03	Affected			0.1792	0.4178		-3	-2	8.3	-43.03
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.3641G>T	R1214L 2D AIThe SynGAP1 missense variant R1214L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of available predictions (four pathogenic versus three benign) suggest a pathogenic impact. This conclusion does not conflict with ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375											-7.058	In-Between	0.510	Ambiguous	Likely Benign										0.114	Likely Benign	-3.65	Deleterious	0.992	Probably Damaging	0.828	Possibly Damaging	2.56	Benign	0.01	Affected			0.1497	0.2988		-3	-2	8.3	-43.03
c.3662G>T	R1221L 2D AIThe SynGAP1 missense variant R1221L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is uncertain because it receives one benign, one pathogenic, and two uncertain votes. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional predictors lean toward pathogenicity, whereas the single high‑accuracy tool predicts benign and the consensus remains inconclusive. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375											-7.995	In-Between	0.480	Ambiguous	Likely Benign										0.150	Likely Benign	-3.71	Deleterious	0.992	Probably Damaging	0.866	Possibly Damaging	2.55	Benign	0.05	Affected			0.1557	0.3206		-3	-2	8.3	-43.03
c.3719G>T	R1240L 2D AIThe SynGAP1 missense variant R1240L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, R1240L is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-10.181	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic										0.372	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.1513	0.3394		-3	-2	8.3	-43.03
c.380G>T	R127L 2D AIThe SynGAP1 missense variant R127L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.711716	Binding	0.333	0.870	0.625											-0.626	Likely Benign	0.643	Likely Pathogenic	Likely Benign										0.127	Likely Benign	-2.02	Neutral	0.080	Benign	0.012	Benign	3.92	Benign	0.01	Affected			0.1965	0.3834		-3	-2	8.3	-43.03
c.3821G>T	R1274L 2D AIThe SynGAP1 missense variant R1274L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the majority of reliable predictors and the high‑accuracy consensus favor a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.613573	Disordered	0.779985	Binding	0.746	0.688	0.625											-5.318	Likely Benign	0.457	Ambiguous	Likely Benign										0.165	Likely Benign	-4.48	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	2.50	Benign	0.01	Affected			0.1657	0.3006		-3	-2	8.3	-43.03
c.3824G>T	R1275L 2D AIThe SynGAP1 missense variant R1275L is listed in ClinVar as benign and is present in gnomAD (ID 6‑33447872‑G‑T). Functional prediction tools show a split: benign calls come from REVEL, ESM1b, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar, while pathogenic calls come from PROVEAN, polyPhen2_HumDiv, and SIFT. Grouping by agreement, the benign‑predicted tools outnumber the pathogenic ones (5 vs 3). High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta results are unavailable. Overall, the computational evidence leans toward a benign effect, consistent with the ClinVar classification and showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.790317	Binding	0.723	0.697	0.500					Likely Benign		1	6-33447872-G-T	1	6.45e-7	-6.052	Likely Benign	0.446	Ambiguous	Likely Benign										0.117	Likely Benign	-4.04	Deleterious	0.800	Possibly Damaging	0.277	Benign	2.55	Benign	0.01	Affected	3.77	5	0.1687	0.3181		-3	-2	8.3	-43.03
c.3923G>T	R1308L 2D AIThe SynGAP1 missense variant R1308L is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. This assessment does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.741537	Disordered	0.930652	Binding	0.378	0.904	0.750											-1.838	Likely Benign	0.257	Likely Benign	Likely Benign										0.360	Likely Benign	-4.04	Deleterious	0.982	Probably Damaging	0.982	Probably Damaging	2.39	Pathogenic	0.00	Affected			0.1751	0.4930		-3	-2	8.3	-43.03
c.3983G>T	R1328L 2D AIThe SynGAP1 missense variant R1328L is listed in gnomAD (ID 6‑33451857‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.911775	Binding	0.360	0.762	0.875								6-33451857-G-T			-3.233	Likely Benign	0.452	Ambiguous	Likely Benign										0.038	Likely Benign	-1.94	Neutral	0.784	Possibly Damaging	0.145	Benign	4.08	Benign	0.01	Affected	3.77	5	0.1978	0.3555		-2	-3	8.3	-43.03
c.4013G>T	R1338L 2D AIThe SynGAP1 missense variant R1338L is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451887‑G‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000								6-33451887-G-T			-3.359	Likely Benign	0.587	Likely Pathogenic	Likely Benign										0.232	Likely Benign	-3.65	Deleterious	0.001	Benign	0.001	Benign	3.78	Benign	0.01	Affected	3.77	5	0.2066	0.5307		-2	-3	8.3	-43.03
c.404G>T	R135L 2D AIThe SynGAP1 missense variant R135L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also indicates pathogenicity. 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 tools, support a pathogenic classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-7.372	In-Between	0.976	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-3.61	Deleterious	0.308	Benign	0.122	Benign	3.70	Benign	0.01	Affected			0.1962	0.4727		-3	-2	8.3	-43.03
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.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.455G>T	R152L 2D AIThe SynGAP1 missense variant R152L 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 (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 indicates that R152L 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		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.501	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.331	Likely Benign	-3.85	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.83	Benign	0.00	Affected			0.2032	0.5249		-3	-2	8.3	-43.03
c.470G>T	R157L 2D AIThe SynGAP1 missense variant R157L 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, 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. Overall, the preponderance of evidence points to 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		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-8.978	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-3.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.81	Benign	0.00	Affected			0.2015	0.3709		-3	-2	8.3	-43.03
c.485G>T	R162L 2D AIThe SynGAP1 missense variant R162L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, giving six concordant benign calls. Two tools predict a pathogenic effect: ESM1b and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250											-9.952	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-1.83	Neutral	0.001	Benign	0.003	Benign	4.05	Benign	0.15	Tolerated			0.1888	0.5894		-3	-2	8.3	-43.03
c.491G>T	R164L 2D AIThe SynGAP1 missense variant R164L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence, including the SGM Consensus, points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for R164L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.512396	Binding	0.317	0.666	0.250											-10.794	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous										0.274	Likely Benign	-3.37	Deleterious	0.001	Benign	0.003	Benign	3.80	Benign	0.00	Affected			0.2137	0.5154		-3	-2	8.3	-43.03
c.509G>T	R170L 2D AIThe SynGAP1 missense variant R170L has no ClinVar entry and is not reported in gnomAD. In silico predictors fall into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools 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 preponderance of pathogenic predictions, including the high‑accuracy consensus, suggests that R170L is most likely pathogenic. 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		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-8.649	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-4.02	Deleterious	0.798	Possibly Damaging	0.319	Benign	3.87	Benign	0.00	Affected			0.1561	0.4310		-3	-2	8.3	-43.03
c.515G>T	R172L 2D AIThe SynGAP1 missense variant R172L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence, including the SGM Consensus, points to a pathogenic impact. This conclusion 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		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375											-8.201	Likely Pathogenic	0.797	Likely Pathogenic	Ambiguous										0.131	Likely Benign	-3.09	Deleterious	0.276	Benign	0.103	Benign	3.99	Benign	0.02	Affected			0.1423	0.4729		-3	-2	8.3	-43.03
c.65G>T	R22I 2D AIThe SynGAP1 missense variant R22I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.441505	Uncertain	0.377	0.891	0.500											-4.849	Likely Benign	0.692	Likely Pathogenic	Likely Benign										0.118	Likely Benign	0.06	Neutral	0.676	Possibly Damaging	0.308	Benign	4.20	Benign	0.00	Affected			0.2120	0.5048		-2	-3	9.0	-43.03
c.701G>T	R234L 2D AIThe SynGAP1 missense variant R234L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy methods show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (7 pathogenic vs. 4 benign) and the pathogenic consensus from the high‑accuracy SGM‑Consensus suggest that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.311558	Uncertain	0.804	0.322	0.000											-11.153	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.38	Ambiguous	0.9	0.50	Ambiguous	0.94	Ambiguous	0.20	Likely Benign	0.734	Likely Pathogenic	-4.64	Deleterious	0.649	Possibly Damaging	0.199	Benign	5.78	Benign	0.11	Tolerated			0.1846	0.4783		-3	-2	8.3	-43.03
c.716G>T	R239I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R239I is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic or likely pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. 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 (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.170161	Structured	0.336504	Uncertain	0.854	0.319	0.000											-19.414	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	4.32	Destabilizing	0.5	2.53	Destabilizing	3.43	Destabilizing	0.83	Ambiguous	0.890	Likely Pathogenic	-7.16	Deleterious	0.985	Probably Damaging	0.724	Possibly Damaging	5.69	Benign	0.00	Affected			0.1480	0.3985		-2	-3	9.0	-43.03
c.743G>T	R248L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R248L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta and FATHMM, whereas the majority of algorithms predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Predictions labeled uncertain are FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the consensus of the available evidence points to a pathogenic effect for R248L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.267126	Uncertain	0.781	0.346	0.250											-12.110	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	1.13	Ambiguous	0.5	0.01	Likely Benign	0.57	Ambiguous	0.67	Ambiguous	0.825	Likely Pathogenic	-6.06	Deleterious	0.979	Probably Damaging	0.680	Possibly Damaging	5.66	Benign	0.03	Affected			0.1616	0.4741		-3	-2	8.3	-43.03
c.74G>T	R25L 2D AIThe SynGAP1 missense variant R25L is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict a pathogenic impact. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically highlight a benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta data are missing. Taken together, the majority of robust predictors and the consensus analysis support a benign classification for R25L. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375											-3.443	Likely Benign	0.484	Ambiguous	Likely Benign										0.121	Likely Benign	-1.59	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	3.97	Benign	0.00	Affected			0.2045	0.4792		-3	-2	8.3	-43.03
c.773G>T	R258L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R258L is not reported in ClinVar and is present in gnomAD (ID 6‑33437678‑G‑T). Prediction tools that agree on a benign effect include FoldX, Rosetta, FATHMM, and the combined Foldetta stability method. Tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools give inconclusive results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.295083	Structured	0.293667	Uncertain	0.894	0.260	0.250								6-33437678-G-T	1	6.20e-7	-13.302	Likely Pathogenic	0.905	Likely Pathogenic	Ambiguous	0.14	Likely Benign	0.2	0.10	Likely Benign	0.12	Likely Benign	0.52	Ambiguous	0.908	Likely Pathogenic	-5.90	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	5.84	Benign	0.01	Affected	3.39	15	0.1606	0.4602		-2	-3	8.3	-43.03
c.776G>T	R259L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R259L is not reported in ClinVar and is absent from gnomAD. Among the available in‑silico predictors, the benign‑predicted tools are Rosetta and FATHMM, while the pathogenic‑predicted tools include SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Foldetta and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of predictions support a pathogenic effect, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.338208	Uncertain	0.885	0.255	0.250											-14.185	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.84	Destabilizing	1.1	0.16	Likely Benign	1.50	Ambiguous	0.64	Ambiguous	0.894	Likely Pathogenic	-6.43	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	5.87	Benign	0.00	Affected			0.1934	0.5499		-3	-2	8.3	-43.03
c.815G>T	R272L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R272L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and premPS. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the majority of evaluated tools predict a pathogenic impact. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.071867	Structured	0.425620	Uncertain	0.925	0.215	0.125											-10.796	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	1.66	Ambiguous	0.3	-0.46	Likely Benign	0.60	Ambiguous	0.41	Likely Benign	0.470	Likely Benign	-4.57	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.75	Pathogenic	0.01	Affected			0.1691	0.4230		-3	-2	8.3	-43.03
c.836G>T	R279L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R279L is reported in gnomAD (ID 6‑33437741‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous 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 impact. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125								6-33437741-G-T	1	6.20e-7	-12.390	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	0.01	Likely Benign	0.2	0.14	Likely Benign	0.08	Likely Benign	0.39	Likely Benign	0.576	Likely Pathogenic	-5.37	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.91	Pathogenic	0.03	Affected	3.39	18	0.1682	0.3266		-2	-3	8.3	-43.03
c.878G>T	R293L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R293L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and premPS, while the remaining evaluated tools (SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict pathogenicity. Uncertain results from FoldX, Rosetta, and Foldetta are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta provides no definitive stability change. Consequently, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125											-15.502	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.2	0.93	Ambiguous	1.25	Ambiguous	0.08	Likely Benign	0.493	Likely Benign	-6.43	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.46	Pathogenic	0.01	Affected			0.1815	0.4987		-3	-2	8.3	-43.03
c.896G>T	R299L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R299L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of consensus predictions favor a pathogenic effect, and the high‑accuracy tools do not overturn this trend. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for R299L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500											-5.171	Likely Benign	0.645	Likely Pathogenic	Likely Benign	1.37	Ambiguous	0.6	0.77	Ambiguous	1.07	Ambiguous	0.59	Ambiguous	0.356	Likely Benign	-4.03	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.02	Affected			0.2027	0.5202		-3	-2	8.3	-43.03
c.92G>T	R31L 2D AIThe SynGAP1 missense variant R31L is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict pathogenic. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically indicate benign: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta data are missing. Overall, the majority of reliable predictions lean toward a benign effect, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.437905	Uncertain	0.324	0.878	0.250											-3.147	Likely Benign	0.360	Ambiguous	Likely Benign										0.149	Likely Benign	-1.79	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	4.01	Benign	0.00	Affected			0.2264	0.5148		-3	-2	8.3	-43.03
c.962G>T	R321L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R321L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign; FoldX and Rosetta individually are inconclusive. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.423273	Uncertain	0.931	0.297	0.125											-11.709	Likely Pathogenic	0.551	Ambiguous	Likely Benign	0.54	Ambiguous	0.0	-0.58	Ambiguous	-0.02	Likely Benign	0.18	Likely Benign	0.451	Likely Benign	-4.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.93	Pathogenic	0.03	Affected			0.1745	0.4048		-3	-2	8.3	-43.03
c.971G>T	R324L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R324L is catalogued in gnomAD (6-33437876‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, and SIFT; pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta (integrating FoldX‑MD and Rosetta outputs) reports a benign stability change. Overall, the majority of evidence points toward a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.257454	Structured	0.426893	Uncertain	0.954	0.397	0.000								6-33437876-G-T	1	6.20e-7	-10.328	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	-0.28	Likely Benign	0.0	-0.08	Likely Benign	-0.18	Likely Benign	0.29	Likely Benign	0.489	Likely Benign	-2.20	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.86	Pathogenic	0.63	Tolerated	3.39	22	0.2310	0.5607		-2	-3	8.3	-43.03
c.986G>T	R329L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R329L has no ClinVar entry and is not reported in gnomAD. Consensus from standard prediction tools shows a split: benign calls come from REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar, while pathogenic calls arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked uncertain (Rosetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the majority of tools lean toward pathogenicity, but the folding‑stability evidence suggests a benign effect. Given the lack of ClinVar annotation, there is no contradiction. The variant is most likely pathogenic based on the preponderance of pathogenic predictions, though the benign folding‑stability result introduces uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-10.186	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	-0.09	Likely Benign	0.4	0.53	Ambiguous	0.22	Likely Benign	0.54	Ambiguous	0.219	Likely Benign	-4.81	Deleterious	0.653	Possibly Damaging	0.361	Benign	4.02	Benign	0.01	Affected			0.1827	0.4121		-3	-2	8.3	-43.03
c.1028T>G	V343G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the preponderance of evidence indicates that V343G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250											-11.332	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	2.49	Destabilizing	0.1	4.40	Destabilizing	3.45	Destabilizing	1.68	Destabilizing	0.421	Likely Benign	-5.84	Deleterious	0.898	Possibly Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.00	Affected			0.1982	0.3341		-1	-3	-4.6	-42.08
c.1037T>G	V346G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). All available in‑silico predictors classify it as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports pathogenic. With all evidence converging on a deleterious impact and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-12.779	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	4.24	Destabilizing	0.2	4.62	Destabilizing	4.43	Destabilizing	2.15	Destabilizing	0.667	Likely Pathogenic	-6.03	Deleterious	0.991	Probably Damaging	0.999	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.2378	0.2522		-1	-3	-4.6	-42.08
c.1043T>G	V348G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348G 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 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 methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among pathogenic predictions and the lack of a benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-12.793	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.2	5.70	Destabilizing	4.84	Destabilizing	2.23	Destabilizing	0.419	Likely Benign	-6.18	Deleterious	0.637	Possibly Damaging	0.989	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.2229	0.2082		-1	-3	-4.6	-42.08
c.1049T>G	V350G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350G lies in the C2 domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, polyPhen‑2 HumDiv, and AlphaMissense‑Optimized. The remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict it to be pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All predictions are available and consistent. Based on the preponderance of pathogenic calls, 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.		C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-12.267	Likely Pathogenic	0.597	Likely Pathogenic	Likely Benign	2.57	Destabilizing	0.0	4.25	Destabilizing	3.41	Destabilizing	1.93	Destabilizing	0.330	Likely Benign	-5.46	Deleterious	0.435	Benign	0.920	Probably Damaging	1.61	Pathogenic	0.02	Affected			0.2316	0.2522		-1	-3	-4.6	-42.08
c.104T>G	V35G 2D AIThe SynGAP1 missense variant V35G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus also predicts benign; 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 benign, and this assessment does not contradict any ClinVar status because the variant is not currently catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.613573	Disordered	0.434838	Uncertain	0.360	0.851	0.375											-3.614	Likely Benign	0.109	Likely Benign	Likely Benign										0.143	Likely Benign	0.66	Neutral	0.693	Possibly Damaging	0.824	Possibly Damaging	4.41	Benign	0.00	Affected			0.1514	0.2618		-1	-3	-4.6	-42.08
c.1094T>G	V365G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a pathogenic effect. Therefore, 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.		C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-13.020	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	4.18	Destabilizing	0.2	4.83	Destabilizing	4.51	Destabilizing	2.18	Destabilizing	0.576	Likely Pathogenic	-5.88	Deleterious	0.688	Possibly Damaging	0.989	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.1835	0.2717		-1	-3	-4.6	-42.08
c.1199T>G	V400G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V400G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are polyPhen‑2 HumDiv and FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.398279	Structured	0.415488	Uncertain	0.951	0.451	0.000											-11.508	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	4.84	Destabilizing	0.1	5.40	Destabilizing	5.12	Destabilizing	2.40	Destabilizing	0.819	Likely Pathogenic	-5.70	Deleterious	0.335	Benign	0.920	Probably Damaging	5.27	Benign	0.00	Affected			0.2296	0.2522		-1	-3	-4.6	-42.08
c.1271T>G	V424G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V424G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic consensus (3 pathogenic vs. 1 benign); and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. No predictions are missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-13.697	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	3.90	Destabilizing	0.1	4.84	Destabilizing	4.37	Destabilizing	2.44	Destabilizing	0.622	Likely Pathogenic	-6.26	Deleterious	0.994	Probably Damaging	1.000	Probably Damaging	3.34	Benign	0.00	Affected			0.1396	0.2029		-1	-3	-4.6	-42.08
c.1301T>G	V434G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as pathogenic. Taken together, the overwhelming majority of evidence indicates a deleterious effect. Therefore, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-12.519	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous	3.08	Destabilizing	0.0	4.37	Destabilizing	3.73	Destabilizing	1.91	Destabilizing	0.564	Likely Pathogenic	-5.16	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.07	Tolerated			0.1758	0.2408		-1	-3	-4.6	-42.08
c.1322T>G	V441G 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V441G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, FoldX, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; the remaining tools (Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenic, and Foldetta is inconclusive. Taken together, the majority of evidence points to a benign effect, but the SGM Consensus and several individual pathogenic predictors introduce uncertainty. Therefore, the variant is most likely benign based on the overall prediction landscape, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-12.380	Likely Pathogenic	0.478	Ambiguous	Likely Benign	0.18	Likely Benign	0.0	1.25	Ambiguous	0.72	Ambiguous	0.95	Ambiguous	0.273	Likely Benign	-5.88	Deleterious	0.841	Possibly Damaging	0.997	Probably Damaging	3.41	Benign	0.24	Tolerated			0.1664	0.1715		-1	-3	-4.6	-42.08
c.1340T>G	V447G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V447G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM, while the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that V447G is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000											-13.648	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	3.81	Destabilizing	0.1	4.62	Destabilizing	4.22	Destabilizing	2.28	Destabilizing	0.499	Likely Benign	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.31	Benign	0.01	Affected			0.1863	0.2240		-1	-3	-4.6	-42.08
c.1355T>G	V452G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V452G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. AlphaMissense‑Optimized remains uncertain. Overall, the preponderance of evidence indicates that V452G is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000											-13.410	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	3.70	Destabilizing	0.1	3.37	Destabilizing	3.54	Destabilizing	2.46	Destabilizing	0.570	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.17	Benign	0.00	Affected			0.1948	0.2567		-1	-3	-4.6	-42.08
c.1418T>G	V473G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the remaining eleven tools (REVEL, 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: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) votes pathogenic, and Foldetta also predicts pathogenic. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic based on the collective evidence, and this conclusion does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000											-14.782	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	3.45	Destabilizing	0.0	3.40	Destabilizing	3.43	Destabilizing	2.69	Destabilizing	0.683	Likely Pathogenic	-6.91	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.13	Benign	0.00	Affected			0.1885	0.2567		-1	-3	-4.6	-42.08
c.1577T>G	V526G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V526G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on pathogenicity include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; no tool predicts it benign. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. All available evidence points to a deleterious effect. Consequently, 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.		GAP	0.139895	Structured	0.023118	Uncertain	0.943	0.403	0.000											-15.811	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	3.21	Destabilizing	0.3	4.79	Destabilizing	4.00	Destabilizing	2.19	Destabilizing	0.935	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.49	Pathogenic	0.00	Affected			0.1636	0.1837		-1	-3	-4.6	-42.08
c.1661T>G	V554G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V554G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, while the remaining eleven tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as pathogenic. No predictions are missing or inconclusive. Overall, the variant is most likely pathogenic based on the collective evidence, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000											-13.879	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	3.31	Destabilizing	0.1	4.13	Destabilizing	3.72	Destabilizing	2.40	Destabilizing	0.594	Likely Pathogenic	-6.96	Deleterious	0.997	Probably Damaging	1.000	Probably Damaging	3.21	Benign	0.00	Affected			0.1619	0.1548		-1	-3	-4.6	-42.08
c.1664T>G	V555G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V555G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on pathogenicity include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; no tool predicts it benign. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as 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 because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.013265	Structured	0.008218	Uncertain	0.943	0.225	0.000											-13.327	Likely Pathogenic	0.899	Likely Pathogenic	Ambiguous	2.07	Destabilizing	0.1	2.22	Destabilizing	2.15	Destabilizing	1.07	Destabilizing	0.798	Likely Pathogenic	-6.35	Deleterious	0.984	Probably Damaging	1.000	Probably Damaging	-1.39	Pathogenic	0.01	Affected			0.1994	0.1677		-1	-3	-4.6	-42.08
c.1679T>G	V560G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V560G 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 SIFT, whereas the majority of tools (REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Uncertain results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized is uncertain, and Foldetta is uncertain. Overall, the preponderance of evidence indicates that V560G 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.		GAP	0.021381	Structured	0.013872	Uncertain	0.853	0.204	0.000											-12.485	Likely Pathogenic	0.799	Likely Pathogenic	Ambiguous	0.66	Ambiguous	0.1	2.12	Destabilizing	1.39	Ambiguous	1.80	Destabilizing	0.753	Likely Pathogenic	-5.87	Deleterious	0.981	Probably Damaging	1.000	Probably Damaging	-1.25	Pathogenic	0.19	Tolerated			0.1738	0.2036		-1	-3	-4.6	-42.08
c.1703T>G	V568G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568G is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID 6‑33440755‑T‑G). Prediction tools that agree on a pathogenic effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. 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 Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000								6-33440755-T-G			-15.135	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	3.39	Destabilizing	0.1	4.45	Destabilizing	3.92	Destabilizing	2.34	Destabilizing	0.933	Likely Pathogenic	-6.81	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.46	Pathogenic	0.00	Affected	3.37	35	0.1822	0.1877		-3	-1	-4.6	-42.08
c.1886T>G	V629G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V629G missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining eleven tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) uniformly predict a pathogenic outcome; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Taken together, the overwhelming majority of evidence indicates that V629G is 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.		GAP	0.040537	Structured	0.034796	Uncertain	0.970	0.236	0.000											-13.150	Likely Pathogenic	0.871	Likely Pathogenic	Ambiguous	3.81	Destabilizing	0.0	4.52	Destabilizing	4.17	Destabilizing	1.94	Destabilizing	0.678	Likely Pathogenic	-6.47	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.07	Benign	0.00	Affected			0.1903	0.2240		-1	-3	-4.6	-42.08
c.2096T>G	V699G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V699G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FATHMM and AlphaMissense‑Optimized, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict; and Foldetta also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000											-11.912	Likely Pathogenic	0.481	Ambiguous	Likely Benign	2.22	Destabilizing	0.0	3.25	Destabilizing	2.74	Destabilizing	1.77	Destabilizing	0.514	Likely Pathogenic	-5.11	Deleterious	0.972	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.01	Affected			0.1830	0.2240		-1	-3	-4.6	-42.08
c.2237T>G	V746G 2D AIThe SynGAP1 missense variant V746G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, V746G is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.576597	Binding	0.336	0.867	0.875											-2.971	Likely Benign	0.113	Likely Benign	Likely Benign										0.035	Likely Benign	-0.89	Neutral	0.136	Benign	0.270	Benign	2.74	Benign	0.02	Affected			0.1897	0.2550		-1	-3	-4.6	-42.08
c.2240T>G	V747G 2D AIThe SynGAP1 missense variant V747G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that V747G is most likely benign, and this conclusion 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.			0.816150	Disordered	0.594069	Binding	0.343	0.873	0.750											-3.883	Likely Benign	0.188	Likely Benign	Likely Benign										0.069	Likely Benign	-1.22	Neutral	0.589	Possibly Damaging	0.917	Probably Damaging	2.56	Benign	0.00	Affected			0.1960	0.2374		-1	-3	-4.6	-42.08
c.2423T>G	V808G 2D AIThe SynGAP1 V808G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of individual predictors (five benign vs. three pathogenic) support a benign classification, and this is not contradicted by any ClinVar annotation. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-6.635	Likely Benign	0.460	Ambiguous	Likely Benign										0.268	Likely Benign	-2.94	Deleterious	0.069	Benign	0.135	Benign	2.27	Pathogenic	0.00	Affected			0.1925	0.3336		-1	-3	-4.6	-42.08
c.2510T>G	V837G 2D AIThe SynGAP1 missense variant V837G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125											-2.599	Likely Benign	0.315	Likely Benign	Likely Benign										0.187	Likely Benign	0.93	Neutral	0.997	Probably Damaging	0.999	Probably Damaging	3.18	Benign	1.00	Tolerated			0.2260	0.2422		-1	-3	-4.6	-42.08
c.2522T>G	V841G 2D AIThe SynGAP1 missense variant V841G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, whereas the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for V841G, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-10.054	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.288	Likely Benign	-4.11	Deleterious	0.997	Probably Damaging	0.999	Probably Damaging	2.51	Benign	0.00	Affected			0.2351	0.2422		-1	-3	-4.6	-42.08
c.2579T>G	V860G 2D AIThe SynGAP1 missense variant V860G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: the benign group includes REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic group contains only SIFT. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from the majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, while Foldetta results are unavailable. Overall, the collective evidence indicates that V860G is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-3.471	Likely Benign	0.173	Likely Benign	Likely Benign										0.198	Likely Benign	-1.54	Neutral	0.012	Benign	0.009	Benign	4.11	Benign	0.00	Affected			0.2312	0.2547		-1	-3	-4.6	-42.08
c.257T>G	V86G 2D AIThe SynGAP1 missense variant V86G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, which evaluates protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence (five pathogenic versus four benign predictions) indicates that V86G 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.			0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500											-4.212	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.130	Likely Benign	-2.50	Deleterious	0.307	Benign	0.824	Possibly Damaging	3.74	Benign	0.00	Affected			0.2321	0.2547		-1	-3	-4.6	-42.08
c.2597T>G	V866G 2D AIThe SynGAP1 missense variant V866G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates benign. 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 benign impact for V866G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.638070	Binding	0.266	0.788	0.250											-1.519	Likely Benign	0.136	Likely Benign	Likely Benign										0.124	Likely Benign	-2.30	Neutral	0.912	Possibly Damaging	0.993	Probably Damaging	2.69	Benign	0.07	Tolerated			0.2548	0.2157		-1	-3	-4.6	-42.08
c.263T>G	V88G 2D AIThe SynGAP1 missense variant V88G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta results are unavailable. Overall, the majority of predictions (5 benign vs. 4 pathogenic) and the lack of a ClinVar pathogenic classification suggest that V88G is most likely benign, with no contradiction to existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-8.588	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.084	Likely Benign	-2.40	Neutral	0.024	Benign	0.208	Benign	3.68	Benign	0.00	Affected			0.2608	0.2609		-1	-3	-4.6	-42.08
c.269T>G	V90G 2D AIThe SynGAP1 missense variant V90G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign verdict. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500											-2.617	Likely Benign	0.358	Ambiguous	Likely Benign										0.094	Likely Benign	-0.55	Neutral	0.024	Benign	0.208	Benign	4.00	Benign	0.00	Affected			0.2047	0.2936		-1	-3	-4.6	-42.08
c.2732T>G	V911G 2D AIThe SynGAP1 missense variant V911G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). All available in silico predictors classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity, so the benign group includes every listed predictor, while the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.724137	Binding	0.327	0.914	0.375											-2.754	Likely Benign	0.222	Likely Benign	Likely Benign										0.124	Likely Benign	-0.04	Neutral	0.004	Benign	0.003	Benign	2.74	Benign	0.16	Tolerated			0.2307	0.3360		-1	-3	-4.6	-42.08
c.2747T>G	V916G 2D AIThe SynGAP1 missense variant V916G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion 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.			0.642678	Disordered	0.835395	Binding	0.308	0.879	0.250											-1.950	Likely Benign	0.091	Likely Benign	Likely Benign										0.093	Likely Benign	-0.63	Neutral	0.666	Possibly Damaging	0.917	Probably Damaging	2.69	Benign	0.05	Affected			0.2420	0.2681		-1	-3	-4.6	-42.08
c.2975T>G	V992G 2D AIThe SynGAP1 missense variant V992G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). All available in silico predictors classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity, so the benign group includes every listed predictor, while the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.754692	Disordered	0.921728	Binding	0.331	0.917	0.750											-1.906	Likely Benign	0.080	Likely Benign	Likely Benign										0.067	Likely Benign	-0.28	Neutral	0.056	Benign	0.086	Benign	4.21	Benign	0.16	Tolerated			0.2114	0.2612		-1	-3	-4.6	-42.08
c.3233T>G	V1078G 2D AIThe SynGAP1 missense variant V1078G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign (3 benign vs 1 pathogenic). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence indicates a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750											-3.270	Likely Benign	0.699	Likely Pathogenic	Likely Benign										0.168	Likely Benign	-0.54	Neutral	0.157	Benign	0.292	Benign	3.85	Benign	0.00	Affected			0.2041	0.2693		-1	-3	-4.6	-42.08
c.329T>G	V110G 2D AIThe SynGAP1 missense variant V110G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.665934	Binding	0.347	0.860	0.750											-4.012	Likely Benign	0.724	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-2.87	Deleterious	0.377	Benign	0.928	Probably Damaging	4.06	Benign	0.00	Affected			0.2302	0.2671		-1	-3	-4.6	-42.08
c.3464T>G	V1155G 2D AIThe SynGAP1 missense variant V1155G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give mixed results: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (benign), and PROVEAN (benign), reports a benign outcome; Foldetta’s stability assessment is unavailable. Overall, the majority of conventional tools lean toward pathogenicity, whereas the high‑accuracy consensus leans benign, leaving the functional impact uncertain. 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.			0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-3.018	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.91	Neutral	0.997	Probably Damaging	0.999	Probably Damaging	2.59	Benign	0.05	Affected			0.2211	0.2374		-1	-3	-4.6	-42.08
c.3473T>G	V1158G 2D AIThe SynGAP1 missense variant V1158G 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, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic outcome. High‑accuracy assessments reinforce this pattern: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict. 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 V1158G is most likely pathogenic, 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.			0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-3.058	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.433	Likely Benign	-4.62	Deleterious	0.997	Probably Damaging	0.999	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.1870	0.3289		-1	-3	-4.6	-42.08
c.3584T>G	V1195G 2D AIThe SynGAP1 missense variant V1195G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Tools that agree on a benign effect are ESM1b and FATHMM. AlphaMissense‑Optimized is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, six of the eight evaluated tools predict pathogenicity while only two predict benign, and no high‑accuracy consensus or folding‑stability evidence contradicts this. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not conflict with the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250											-5.463	Likely Benign	0.881	Likely Pathogenic	Ambiguous										0.586	Likely Pathogenic	-2.81	Deleterious	0.998	Probably Damaging	1.000	Probably Damaging	5.55	Benign	0.01	Affected			0.2005	0.2100		-1	-3	-4.6	-42.08
c.3806T>G	V1269G 2D AIThe SynGAP1 missense variant V1269G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus is pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-9.927	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.420	Likely Benign	-5.91	Deleterious	0.995	Probably Damaging	0.999	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2180	0.2557		-1	-3	-4.6	-42.08
c.3926T>G	V1309G 2D AIThe SynGAP1 missense variant V1309G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation because the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.712013	Disordered	0.948596	Binding	0.402	0.907	0.750											-2.618	Likely Benign	0.160	Likely Benign	Likely Benign										0.326	Likely Benign	-3.40	Deleterious	0.391	Benign	0.767	Possibly Damaging	2.40	Pathogenic	0.00	Affected			0.1901	0.2144		-1	-3	-4.6	-42.08
c.626T>G	V209G 2D AIThe SynGAP1 missense variant V209G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a pathogenic classification; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. Taken together, the overwhelming majority of computational evidence indicates that V209G is 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.		PH	0.247041	Structured	0.397624	Uncertain	0.874	0.331	0.125											-13.763	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.05	Destabilizing	0.5	3.99	Destabilizing	3.52	Destabilizing	1.27	Destabilizing	0.390	Likely Benign	-5.49	Deleterious	0.829	Possibly Damaging	0.995	Probably Damaging	3.65	Benign	0.04	Affected			0.1600	0.2035		-1	-3	-4.6	-42.08
c.665T>G	V222G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V222G resides in the PH domain. ClinVar has no entry for this variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining eleven tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Thus, the variant is most likely pathogenic based on the collective predictions, 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.		PH	0.116183	Structured	0.402706	Uncertain	0.885	0.310	0.125											-14.857	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	4.54	Destabilizing	0.4	5.25	Destabilizing	4.90	Destabilizing	2.05	Destabilizing	0.962	Likely Pathogenic	-6.05	Deleterious	0.987	Probably Damaging	0.998	Probably Damaging	5.21	Benign	0.00	Affected			0.1678	0.1996		-1	-3	-4.6	-42.08
c.71T>G	V24G 2D AIThe SynGAP1 missense variant V24G is not reported in ClinVar (ClinVar status: not present) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500											-2.673	Likely Benign	0.256	Likely Benign	Likely Benign										0.178	Likely Benign	-1.67	Neutral	0.026	Benign	0.049	Benign	3.77	Benign	0.00	Affected			0.2081	0.3105		-1	-3	-4.6	-42.08
c.749T>G	V250G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V250G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default, while only FATHMM predicts a benign outcome. Uncertain results are reported by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is pathogenic. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.244075	Uncertain	0.778	0.324	0.125											-11.255	Likely Pathogenic	0.917	Likely Pathogenic	Ambiguous	1.65	Ambiguous	0.3	3.18	Destabilizing	2.42	Destabilizing	2.08	Destabilizing	0.900	Likely Pathogenic	-5.90	Deleterious	0.879	Possibly Damaging	0.997	Probably Damaging	5.75	Benign	0.00	Affected			0.1884	0.1996		-1	-3	-4.6	-42.08
c.779T>G	V260G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V260G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FATHMM and AlphaMissense‑Optimized, while the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, and Foldetta are uncertain and therefore not considered evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (3 pathogenic vs. 1 benign). Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for V260G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.254060	Structured	0.382651	Uncertain	0.888	0.259	0.250											-9.300	Likely Pathogenic	0.644	Likely Pathogenic	Likely Benign	1.00	Ambiguous	0.3	1.86	Ambiguous	1.43	Ambiguous	1.40	Destabilizing	0.817	Likely Pathogenic	-4.20	Deleterious	0.991	Probably Damaging	0.999	Probably Damaging	5.76	Benign	0.00	Affected			0.1844	0.1949		-1	-3	-4.6	-42.08
c.788T>G	V263G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V263G missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized; those that agree on a pathogenic effect are REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence points to a pathogenic impact for V263G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.268042	Structured	0.356141	Uncertain	0.918	0.257	0.000											-10.388	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	2.27	Destabilizing	0.2	1.63	Ambiguous	1.95	Ambiguous	1.88	Destabilizing	0.820	Likely Pathogenic	-4.59	Deleterious	0.991	Probably Damaging	0.999	Probably Damaging	6.07	Benign	0.01	Affected			0.1790	0.1868		-1	-3	-4.6	-42.08
c.917T>G	V306G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V306G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a pathogenic effect. Therefore, 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.		C2	0.363090	Structured	0.315026	Uncertain	0.896	0.287	0.125											-12.313	Likely Pathogenic	0.795	Likely Pathogenic	Ambiguous	4.39	Destabilizing	0.2	5.89	Destabilizing	5.14	Destabilizing	2.46	Destabilizing	0.529	Likely Pathogenic	-5.48	Deleterious	0.998	Probably Damaging	1.000	Probably Damaging	1.78	Pathogenic	0.00	Affected			0.1874	0.2035		-1	-3	-4.6	-42.08
c.959T>G	V320G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V320G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools cluster into two agreement groups: the single benign prediction comes from REVEL, while the pathogenic group includes FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain; the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—returns pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. Overall, the preponderance of evidence indicates that V320G is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.185198	Structured	0.419626	Uncertain	0.905	0.266	0.125											-9.043	Likely Pathogenic	0.816	Likely Pathogenic	Ambiguous	2.15	Destabilizing	1.1	1.87	Ambiguous	2.01	Destabilizing	1.48	Destabilizing	0.438	Likely Benign	-5.74	Deleterious	0.958	Probably Damaging	0.999	Probably Damaging	1.89	Pathogenic	0.02	Affected			0.1688	0.1949		-1	-3	-4.6	-42.08
c.1070A>C	H357P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357P missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools give uncertain results: Foldetta (protein‑folding stability) and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-7.953	In-Between	0.267	Likely Benign	Likely Benign	0.17	Likely Benign	0.9	3.52	Destabilizing	1.85	Ambiguous	-0.06	Likely Benign	0.197	Likely Benign	-2.70	Deleterious	0.936	Possibly Damaging	0.469	Possibly Damaging	4.18	Benign	0.17	Tolerated			0.2433	0.4468		0	-2	1.6	-40.02
c.107A>C	H36P 2D AIThe SynGAP1 missense variant H36P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375											-2.285	Likely Benign	0.066	Likely Benign	Likely Benign										0.171	Likely Benign	-1.23	Neutral	0.182	Benign	0.046	Benign	4.16	Benign	0.00	Affected			0.2097	0.4723		0	-2	1.6	-40.02
c.1280A>C	H427P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Two tools are uncertain: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate a pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification for H427P, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-11.098	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	4.74	Destabilizing	0.1	7.61	Destabilizing	6.18	Destabilizing	0.68	Ambiguous	0.324	Likely Benign	-4.22	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.51	Benign	0.01	Affected			0.2061	0.3442		0	-2	1.6	-40.02
c.1358A>C	H453P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H453P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM. The majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-15.704	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.29	Destabilizing	0.4	7.04	Destabilizing	5.17	Destabilizing	0.84	Ambiguous	0.488	Likely Benign	-9.88	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.04	Affected			0.2115	0.3938		0	-2	1.6	-40.02
c.1442A>C	H481P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H481P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM. Those that predict a pathogenic effect comprise SGM Consensus (Likely Pathogenic), PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and PROVEAN. Tools with inconclusive results are Foldetta (Uncertain) and premPS (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta remains uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-10.205	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.3	3.69	Destabilizing	1.61	Ambiguous	0.67	Ambiguous	0.385	Likely Benign	-5.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.26	Tolerated			0.1979	0.3553		0	-2	1.6	-40.02
c.1616A>C	H539P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H539P missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only FoldX, whereas all other evaluated algorithms—REVEL, Rosetta, Foldetta, premPS, 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 impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Taken together, the overwhelming 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	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000											-15.182	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.3	9.08	Destabilizing	4.65	Destabilizing	1.03	Destabilizing	0.913	Likely Pathogenic	-9.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.29	Pathogenic	0.01	Affected			0.1900	0.2794		0	-2	1.6	-40.02
c.1673A>C	H558P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H558P 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 SIFT and AlphaMissense‑Optimized; those that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Overall, the majority of tools, including the high‑accuracy ones, indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.033407	Structured	0.011039	Uncertain	0.897	0.200	0.000											-13.706	Likely Pathogenic	0.675	Likely Pathogenic	Likely Benign	0.63	Ambiguous	0.2	6.93	Destabilizing	3.78	Destabilizing	0.94	Ambiguous	0.782	Likely Pathogenic	-6.28	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	-1.25	Pathogenic	0.09	Tolerated			0.2061	0.2405		0	-2	1.6	-40.02
c.194A>C	H65P 2D AIThe SynGAP1 missense variant H65P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for H65P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.476188	Uncertain	0.458	0.758	0.125											-1.732	Likely Benign	0.479	Ambiguous	Likely Benign										0.103	Likely Benign	-1.47	Neutral	0.676	Possibly Damaging	0.227	Benign	4.16	Benign	0.00	Affected			0.1915	0.3701		0	-2	1.6	-40.02
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.2612A>C	H871P 2D AIThe SynGAP1 missense variant H871P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.679301	Binding	0.279	0.858	0.250											-3.420	Likely Benign	0.074	Likely Benign	Likely Benign										0.207	Likely Benign	-0.91	Neutral	0.510	Possibly Damaging	0.206	Benign	2.63	Benign	0.18	Tolerated			0.2163	0.3757		0	-2	1.6	-40.02
c.26A>C	H9P 2D AIThe SynGAP1 missense variant H9P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750											-2.838	Likely Benign	0.061	Likely Benign	Likely Benign										0.224	Likely Benign	-0.16	Neutral	0.107	Benign	0.006	Benign	4.19	Benign	0.00	Affected			0.2644	0.5169		0	-2	1.6	-40.02
c.2798A>C	H933P 2D AIThe SynGAP1 missense variant H933P 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 ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, six tools predict pathogenicity versus three predicting benign, and the high‑accuracy benign prediction is outweighed by the majority of pathogenic calls. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-3.890	Likely Benign	0.332	Likely Benign	Likely Benign										0.508	Likely Pathogenic	-5.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.36	Pathogenic	0.02	Affected			0.1821	0.4400		0	-2	1.6	-40.02
c.2834A>C	H945P 2D AIThe SynGAP1 missense variant H945P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of benign predictions and the lack of pathogenic evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.982235	Disordered	0.849210	Binding	0.386	0.923	0.750											-1.962	Likely Benign	0.055	Likely Benign	Likely Benign										0.420	Likely Benign	-0.34	Neutral	0.012	Benign	0.047	Benign	5.04	Benign	0.05	Affected			0.2730	0.3907		0	-2	1.6	-40.02
c.284A>C	H95P 2D AIThe SynGAP1 missense variant H95P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while the single pathogenic call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) confirms a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence indicates that H95P is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.590542	Binding	0.335	0.875	0.625											-1.611	Likely Benign	0.045	Likely Benign	Likely Benign										0.164	Likely Benign	-1.66	Neutral	0.000	Benign	0.000	Benign	4.19	Benign	0.00	Affected			0.2244	0.3704		0	-2	1.6	-40.02
c.2852A>C	H951P 2D AIThe SynGAP1 missense variant H951P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion is consistent with the lack 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 Benign		0.988291	Disordered	0.901477	Binding	0.415	0.925	0.750											-2.798	Likely Benign	0.051	Likely Benign	Likely Benign										0.312	Likely Benign	-0.06	Neutral	0.000	Benign	0.001	Benign	5.43	Benign	0.14	Tolerated			0.2745	0.3707		0	-2	1.6	-40.02
c.2870A>C	H957P 2D AIThe SynGAP1 H957P missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a Likely Benign classification (3 benign vs. 1 pathogenic). AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.968874	Binding	0.362	0.915	0.750											-6.347	Likely Benign	0.061	Likely Benign	Likely Benign										0.244	Likely Benign	-0.61	Neutral	0.453	Possibly Damaging	0.105	Benign	2.42	Pathogenic	0.13	Tolerated			0.2300	0.4701		0	-2	1.6	-40.02
c.2873A>C	H958P 2D AIThe SynGAP1 missense variant H958P is listed in ClinVar as a benign alteration (ClinVar ID 1006798.0) and is present in the gnomAD database (gnomAD ID 6‑33443425‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar benign status, showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.976011	Binding	0.371	0.913	0.750					Benign		1	6-33443425-A-C	2	1.24e-6	-8.369	Likely Pathogenic	0.068	Likely Benign	Likely Benign										0.204	Likely Benign	-0.36	Neutral	0.925	Possibly Damaging	0.316	Benign	4.14	Benign	0.10	Tolerated	3.77	5	0.2290	0.4701		0	-2	1.6	-40.02
c.2876A>C	H959P 2D AIThe SynGAP1 missense variant H959P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.980566	Binding	0.333	0.905	0.750											-8.902	Likely Pathogenic	0.070	Likely Benign	Likely Benign										0.232	Likely Benign	-0.61	Neutral	0.453	Possibly Damaging	0.105	Benign	4.14	Benign	0.38	Tolerated			0.2284	0.4901		0	-2	1.6	-40.02
c.2879A>C	H960P 2D AIThe SynGAP1 missense variant H960P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.987911	Disordered	0.983385	Binding	0.380	0.901	0.750											-8.672	Likely Pathogenic	0.064	Likely Benign	Likely Benign										0.119	Likely Benign	-0.95	Neutral	0.494	Possibly Damaging	0.170	Benign	4.18	Benign	0.28	Tolerated			0.2157	0.4901		0	-2	1.6	-40.02
c.2882A>C	H961P 2D AIThe SynGAP1 missense variant H961P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while only SIFT and ESM1b predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Consequently, the collective evidence indicates that H961P is most likely benign, and this conclusion is not in 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 Benign		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750											-8.434	Likely Pathogenic	0.071	Likely Benign	Likely Benign										0.210	Likely Benign	-0.58	Neutral	0.000	Benign	0.000	Benign	4.15	Benign	0.02	Affected			0.2061	0.4701		0	-2	1.6	-40.02
c.2885A>C	H962P 2D AIThe SynGAP1 missense variant H962P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.984483	Binding	0.369	0.886	0.750											-8.419	Likely Pathogenic	0.066	Likely Benign	Likely Benign										0.197	Likely Benign	-0.94	Neutral	0.748	Possibly Damaging	0.170	Benign	4.16	Benign	0.07	Tolerated			0.2011	0.4352		0	-2	1.6	-40.02
c.2888A>C	H963P 2D AIThe SynGAP1 missense variant H963P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only ESM1b predicts a pathogenic outcome, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports benign, and the SGM Consensus also indicates Likely Benign; Foldetta data are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not in conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.983973	Binding	0.325	0.886	0.750											-8.158	Likely Pathogenic	0.074	Likely Benign	Likely Benign										0.223	Likely Benign	-1.10	Neutral	0.000	Benign	0.001	Benign	4.10	Benign	0.14	Tolerated			0.2101	0.4487		0	-2	1.6	-40.02
c.2891A>C	H964P 2D AIThe SynGAP1 missense variant H964P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while the only pathogenic call comes from SIFT. ESM1b is uncertain, and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta stability analysis is unavailable. Overall, the collective evidence points to a benign impact for H964P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.990547	Disordered	0.982486	Binding	0.364	0.886	0.750											-7.466	In-Between	0.063	Likely Benign	Likely Benign										0.156	Likely Benign	-0.34	Neutral	0.000	Benign	0.000	Benign	4.12	Benign	0.04	Affected			0.1978	0.4301		0	-2	1.6	-40.02
c.2894A>C	H965P 2D AIThe SynGAP1 missense variant H965P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool predicts pathogenicity. The high‑accuracy consensus methods also support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this prediction does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988505	Disordered	0.978700	Binding	0.342	0.882	0.750											-6.835	Likely Benign	0.059	Likely Benign	Likely Benign										0.245	Likely Benign	-0.69	Neutral	0.000	Benign	0.001	Benign	4.06	Benign	0.19	Tolerated			0.2342	0.4901		0	-2	1.6	-40.02
c.2897A>C	H966P 2D AIThe SynGAP1 missense variant H966P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.976962	Disordered	0.974672	Binding	0.378	0.879	0.750											-5.831	Likely Benign	0.064	Likely Benign	Likely Benign										0.279	Likely Benign	-0.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.72	Tolerated			0.2168	0.4301		0	-2	1.6	-40.02
c.2939A>C	H980P 2D AIThe SynGAP1 missense variant H980P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools largely favor a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, two tools—polyPhen‑2 HumDiv and SIFT—classify the change as pathogenic. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus (majority vote) is likely benign; no Foldetta stability data are available. Overall, the preponderance of evidence points to a benign effect for H980P, and this conclusion is not in conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.974598	Binding	0.309	0.892	0.625											-3.071	Likely Benign	0.151	Likely Benign	Likely Benign										0.136	Likely Benign	-1.70	Neutral	0.802	Possibly Damaging	0.432	Benign	4.15	Benign	0.00	Affected			0.2274	0.4301		0	-2	1.6	-40.02
c.293A>C	H98P 2D AIThe SynGAP1 missense variant H98P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.631713	Binding	0.348	0.872	0.625											-1.460	Likely Benign	0.069	Likely Benign	Likely Benign										0.275	Likely Benign	-0.83	Neutral	0.659	Possibly Damaging	0.024	Benign	4.20	Benign	0.00	Affected			0.2062	0.4669		0	-2	1.6	-40.02
c.3005A>C	H1002P 2D AIThe SynGAP1 missense variant H1002P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the majority of predictions and the high‑accuracy consensus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500											-4.616	Likely Benign	0.242	Likely Benign	Likely Benign										0.213	Likely Benign	-2.02	Neutral	0.989	Probably Damaging	0.874	Possibly Damaging	2.77	Benign	0.28	Tolerated			0.2015	0.3738		0	-2	1.6	-40.02
c.3011A>C	H1004P 2D AIThe SynGAP1 missense variant H1004P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and the high‑accuracy AlphaMissense‑Optimized model. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign majority vote. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction between the predictions and ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750											-3.686	Likely Benign	0.460	Ambiguous	Likely Benign										0.236	Likely Benign	-2.69	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.72	Benign	0.18	Tolerated			0.2076	0.4643		0	-2	1.6	-40.02
c.302A>C	H101P 2D AIThe SynGAP1 H101P missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.688356	Binding	0.370	0.884	0.625											-2.042	Likely Benign	0.069	Likely Benign	Likely Benign										0.170	Likely Benign	0.89	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.17	Benign	0.00	Affected			0.1777	0.3589		0	-2	1.6	-40.02
c.3089A>C	H1030P 2D AIThe SynGAP1 missense variant H1030P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that H1030P is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.849326	Disordered	0.995856	Binding	0.375	0.735	0.500											-2.185	Likely Benign	0.148	Likely Benign	Likely Benign										0.154	Likely Benign	-0.78	Neutral	0.812	Possibly Damaging	0.298	Benign	2.77	Benign	0.02	Affected			0.1872	0.4225		0	-2	1.6	-40.02
c.3410A>C	H1137P 2D AIThe SynGAP1 missense variant H1137P is listed in ClinVar as a benign alteration (ClinVar ID 3685596.0) and is present in the gnomAD database (gnomAD ID 6‑33444445‑A‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (derived from the same four high‑accuracy predictors) also indicates benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions, including the most reliable tools, support a benign classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.756488	Binding	0.314	0.879	0.875					Benign		1	6-33444445-A-C	12	7.44e-6	-2.098	Likely Benign	0.054	Likely Benign	Likely Benign										0.419	Likely Benign	-1.93	Neutral	0.925	Possibly Damaging	0.703	Possibly Damaging	5.29	Benign	0.00	Affected	4.32	4	0.2045	0.4501		-2	0	1.6	-40.02
c.3488A>C	H1163P 2D AIThe SynGAP1 missense variant H1163P 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 SIFT, ESM1b, and FATHMM, while those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, more tools predict pathogenicity than benignity (5 vs. 3), and there is no ClinVar record to contradict this assessment. 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.			0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375											-2.023	Likely Benign	0.815	Likely Pathogenic	Ambiguous										0.578	Likely Pathogenic	-3.19	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.39	Benign	0.10	Tolerated			0.2015	0.3900		0	-2	1.6	-40.02
c.3515A>C	H1172P 2D AIThe SynGAP1 missense variant H1172P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.673805	Binding	0.465	0.758	0.625											-2.871	Likely Benign	0.653	Likely Pathogenic	Likely Benign										0.403	Likely Benign	-2.09	Neutral	0.925	Possibly Damaging	0.529	Possibly Damaging	5.42	Benign	0.02	Affected			0.2033	0.4128		0	-2	1.6	-40.02
c.3608A>C	H1203P 2D AIThe SynGAP1 missense variant H1203P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.618285	Disordered	0.527023	Binding	0.892	0.589	0.250											-11.286	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.485	Likely Benign	-2.10	Neutral	0.975	Probably Damaging	0.767	Possibly Damaging	5.47	Benign	0.26	Tolerated			0.1742	0.2820		0	-2	1.6	-40.02
c.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.3830A>C	H1277P 2D AIThe SynGAP1 missense variant H1277P is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33447878‑A‑C). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the lack of a ClinVar pathogenic annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.805725	Binding	0.562	0.718	0.750								6-33447878-A-C			-3.829	Likely Benign	0.324	Likely Benign	Likely Benign										0.237	Likely Benign	-7.14	Deleterious	0.586	Possibly Damaging	0.287	Benign	2.12	Pathogenic	0.00	Affected	3.77	5	0.2266	0.3393		-2	0	1.6	-40.02
c.4028A>C	H1343P 2D AIThe SynGAP1 missense variant H1343P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.983646	Binding	0.350	0.677	0.875											-2.696	Likely Benign	0.094	Likely Benign	Likely Benign										0.126	Likely Benign	-1.23	Neutral	0.659	Possibly Damaging	0.104	Benign	4.02	Benign	0.00	Affected			0.2333	0.4220		0	-2	1.6	-40.02
c.503A>C	H168P 2D AIThe SynGAP1 missense variant H168P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Taken together, the preponderance of evidence points to a benign 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 Benign		0.433034	Structured	0.502450	Binding	0.402	0.678	0.125											-7.686	In-Between	0.124	Likely Benign	Likely Benign										0.279	Likely Benign	-1.66	Neutral	0.072	Benign	0.043	Benign	4.19	Benign	0.02	Affected			0.2004	0.3960		0	-2	1.6	-40.02
c.542A>C	H181P 2D AISynGAP1 H181P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign calls come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, 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 support this: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus indicates pathogenicity; Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic effect, 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		0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500											-13.151	Likely Pathogenic	0.737	Likely Pathogenic	Likely Benign										0.236	Likely Benign	-3.27	Deleterious	0.940	Possibly Damaging	0.360	Benign	4.14	Benign	0.04	Affected			0.1783	0.3169		0	-2	1.6	-40.02
c.548A>C	H183P 2D AIThe SynGAP1 missense variant H183P 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, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-18.527	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.410	Likely Benign	-7.18	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.79	Benign	0.01	Affected			0.2143	0.3712		0	-2	1.6	-40.02
c.629A>C	H210P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H210P 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; all other evaluated algorithms—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 from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also 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 classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.144935	Structured	0.390904	Uncertain	0.872	0.298	0.125											-14.634	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	2.26	Destabilizing	0.5	2.80	Destabilizing	2.53	Destabilizing	1.00	Destabilizing	0.512	Likely Pathogenic	-8.55	Deleterious	0.989	Probably Damaging	0.795	Possibly Damaging	3.09	Benign	0.00	Affected			0.1805	0.3175		0	-2	1.6	-40.02
c.89A>C	H30P 2D AIThe SynGAP1 H30P missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-1.933	Likely Benign	0.077	Likely Benign	Likely Benign										0.202	Likely Benign	-2.77	Deleterious	0.676	Possibly Damaging	0.599	Possibly Damaging	3.89	Benign	0.00	Affected			0.2527	0.4723		0	-2	1.6	-40.02
c.932A>C	H311P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H311P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign outcome; the remaining predictions are uncertain (FoldX, Foldetta, premPS, AlphaMissense‑Optimized). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the majority of evidence points to a deleterious impact on protein function. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for H311P. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125											-10.454	Likely Pathogenic	0.869	Likely Pathogenic	Ambiguous	1.57	Ambiguous	0.6	2.39	Destabilizing	1.98	Ambiguous	0.74	Ambiguous	0.724	Likely Pathogenic	-7.76	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.87	Pathogenic	0.01	Affected			0.2173	0.4172		0	-2	1.6	-40.02
c.977A>C	H326P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions are absent; pathogenic predictions are reported by REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). The only inconclusive result is premPS, which is listed as Uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Pathogenic. Based on the consensus of these predictions, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-18.452	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	2.67	Destabilizing	0.3	2.59	Destabilizing	2.63	Destabilizing	0.88	Ambiguous	0.711	Likely Pathogenic	-8.73	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.92	Pathogenic	0.03	Affected			0.2383	0.4492		0	-2	1.6	-40.02
c.1072T>A	F358I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F358I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports an uncertain impact. Overall, the preponderance of evidence points to a pathogenic effect for F358I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-10.636	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.93	Ambiguous	0.2	1.66	Ambiguous	1.30	Ambiguous	0.95	Ambiguous	0.393	Likely Benign	-4.45	Deleterious	0.993	Probably Damaging	0.977	Probably Damaging	4.07	Benign	0.13	Tolerated			0.2331	0.2821		1	0	1.7	-34.02
c.1072T>C	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L 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, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.290	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1074C>A	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L 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, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1074C>G	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L 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, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the majority of reliable tools predict a pathogenic impact for F358L. This conclusion does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1258T>A	F420I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420I 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, while pathogenic calls are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-12.567	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.88	Destabilizing	0.0	3.64	Destabilizing	3.26	Destabilizing	1.25	Destabilizing	0.330	Likely Benign	-5.46	Deleterious	0.575	Possibly Damaging	0.059	Benign	3.22	Benign	0.02	Affected			0.1864	0.2113		1	0	1.7	-34.02
c.1258T>C	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise the SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated predictors (six pathogenic vs. five benign) indicate that F420L is most likely pathogenic, 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	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	0.262	Likely Benign	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	0.2053	0.3016		2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1260T>A	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise the SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated predictors (six pathogenic vs. five benign) indicate that F420L is most likely pathogenic, 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	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	0.146	Likely Benign	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	0.2053	0.3016		2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1260T>G	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is listed in ClinVar (ID 1397885.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Those that predict a pathogenic effect comprise premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, Foldetta) yield inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus also as pathogenic, while Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar “Uncertain” status but suggests 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	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000					Uncertain		1				-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	0.146	Likely Benign	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	0.2053	0.3016		2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1390T>A	F464I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, while all other evaluated algorithms—including SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-11.210	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	4.77	Destabilizing	0.2	4.35	Destabilizing	4.56	Destabilizing	1.23	Destabilizing	0.539	Likely Pathogenic	-5.97	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.44	Benign	0.03	Affected			0.1439	0.2002		1	0	1.7	-34.02
c.1390T>C	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.435	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>A	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>G	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1426T>A	F476I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F476I has no ClinVar entry and is not reported in gnomAD. Functional prediction tools fall into two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, and FATHMM; pathogenic predictions come from FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive and is treated as unavailable. With seven tools indicating pathogenicity versus five indicating benign, and two high‑accuracy tools supporting pathogenicity, the evidence points to a likely pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-12.617	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.90	Destabilizing	0.1	3.09	Destabilizing	3.50	Destabilizing	0.39	Likely Benign	0.239	Likely Benign	-1.23	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.50	Benign	0.37	Tolerated			0.1383	0.2202		1	0	1.7	-34.02
c.1426T>C	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.196	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1428C>A	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.180	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1428C>G	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438460‑C‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that returned uncertain results—FoldX, Rosetta, Foldetta, and premPS—do not contribute to the assessment. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, with two pathogenic and two benign calls; Foldetta also reports an uncertain stability change. Overall, the balance of evidence favors a pathogenic effect for F476L, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000					Uncertain		2	6-33438460-C-G	4	2.48e-6	-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.180	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.142T>A	F48I 2D AIThe SynGAP1 missense variant F48I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while SIFT and AlphaMissense‑Default predict a pathogenic impact. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further clarify the variant’s likely benign nature: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors benign; AlphaMissense‑Optimized remains uncertain, and Foldetta (which would evaluate protein‑folding stability) is unavailable. Overall, the balance of evidence points to a benign classification, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-7.994	In-Between	0.808	Likely Pathogenic	Ambiguous										0.108	Likely Benign	-1.67	Neutral	0.092	Benign	0.050	Benign	3.99	Benign	0.00	Affected			0.2561	0.2301		1	0	1.7	-34.02
c.142T>C	F48L 2D AIThe SynGAP1 missense variant F48L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence and no Foldetta data is available. Thus, the variant is most likely benign based on the consensus of available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-4.955	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.108	Likely Benign	-1.56	Neutral	0.022	Benign	0.016	Benign	4.16	Benign	0.00	Affected			0.2641	0.3082		2	0	1.0	-34.02
c.144C>A	F48L 2D AIThe SynGAP1 missense variant F48L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence and no Foldetta data is available. Thus, the variant is most likely benign based on the consensus of available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-4.955	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.052	Likely Benign	-1.56	Neutral	0.022	Benign	0.016	Benign	4.16	Benign	0.00	Affected			0.2641	0.3082		2	0	1.0	-34.02
c.144C>G	F48L 2D AIThe SynGAP1 missense variant F48L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence and no Foldetta data is available. Thus, the variant is most likely benign based on the consensus of available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-4.955	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.053	Likely Benign	-1.56	Neutral	0.022	Benign	0.016	Benign	4.16	Benign	0.00	Affected			0.2641	0.3082		2	0	1.0	-34.02
c.1450T>A	F484I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484I 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. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive or missing. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-16.197	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	5.62	Destabilizing	0.2	5.62	Destabilizing	5.62	Destabilizing	1.33	Destabilizing	0.399	Likely Benign	-5.70	Deleterious	0.894	Possibly Damaging	0.332	Benign	2.74	Benign	0.00	Affected			0.1516	0.1885		1	0	1.7	-34.02
c.1450T>C	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic vs. 1 benign) and therefore also indicates pathogenicity. AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy consensus supports a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.275	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1452C>A	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic vs. 1 benign) and therefore also indicates pathogenicity. AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy consensus supports a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.214	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1452C>G	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy methods reinforce the pathogenic signal. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.214	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1537T>A	F513I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513I is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely converge on a deleterious effect: SIFT is the sole benign caller, whereas REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. Grouping by consensus, the single benign prediction (SIFT) is outweighed by the 13 pathogenic calls. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-12.003	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.42	Destabilizing	0.4	2.18	Destabilizing	2.80	Destabilizing	1.12	Destabilizing	0.766	Likely Pathogenic	-5.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.24	Pathogenic	0.22	Tolerated			0.1473	0.1766		1	0	1.7	-34.02
c.1537T>C	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a deleterious effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No evidence from FoldX or Rosetta is considered decisive. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.674	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1539C>A	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic)—all predict a deleterious effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. No evidence from FoldX or Rosetta is considered decisive. Overall, the preponderance of predictions indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.537	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1539C>G	F513L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F513L missense variant has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is inconclusive and therefore not considered evidence. FoldX and Rosetta predictions are uncertain and treated as unavailable. Overall, the preponderance of evidence indicates that F513L is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.370	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.36	Ambiguous	0.2	1.63	Ambiguous	1.50	Ambiguous	1.14	Destabilizing	0.537	Likely Pathogenic	-5.63	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.07	Pathogenic	0.19	Tolerated			0.1645	0.2447		2	0	1.0	-34.02
c.1681T>A	F561I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561I is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (variant ID 6‑33440733‑T‑A). Prediction tools that agree on a benign effect include only SIFT. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts 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 (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000								6-33440733-T-A	1	6.32e-7	-11.708	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	3.82	Destabilizing	0.1	2.13	Destabilizing	2.98	Destabilizing	1.46	Destabilizing	0.710	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.06	Pathogenic	0.09	Tolerated	3.37	35	0.1825	0.1925		0	1	1.7	-34.02
c.1681T>C	F561L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only SIFT, whereas the remaining evaluated algorithms (REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic or likely pathogenic outcome; FoldX is listed as uncertain and is therefore not considered evidence for either side. 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) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for F561L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-8.947	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.2	2.52	Destabilizing	2.12	Destabilizing	1.39	Destabilizing	0.656	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-0.81	Pathogenic	0.32	Tolerated			0.1911	0.2629		2	0	1.0	-34.02
c.1683C>A	F561L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the remaining tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-8.947	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.2	2.52	Destabilizing	2.12	Destabilizing	1.39	Destabilizing	0.492	Likely Benign	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-0.81	Pathogenic	0.32	Tolerated			0.1911	0.2629		2	0	1.0	-34.02
c.1683C>G	F561L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the remaining tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-8.947	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.2	2.52	Destabilizing	2.12	Destabilizing	1.39	Destabilizing	0.493	Likely Benign	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-0.81	Pathogenic	0.32	Tolerated			0.1911	0.2629		2	0	1.0	-34.02
c.1705T>A	F569I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569I is not listed in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classifies the substitution as pathogenic. No predictor reports a benign outcome, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-15.362	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.75	Destabilizing	0.2	4.23	Destabilizing	3.99	Destabilizing	1.51	Destabilizing	0.903	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.1950	0.1973		1	0	1.7	-34.02
c.1705T>C	F569L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none; all available predictors that provide a verdict classify the variant as pathogenic, with the exception of FoldX and Foldetta, whose results are uncertain and therefore treated as unavailable. The high‑accuracy predictors give the following: AlphaMissense‑Optimized predicts pathogenic; 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, is uncertain and thus not considered evidence. Based on the overwhelming consensus of pathogenic predictions and the lack of contrary evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-9.784	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.86	Ambiguous	0.1	2.04	Destabilizing	1.45	Ambiguous	1.28	Destabilizing	0.804	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.13	Pathogenic	0.05	Affected			0.1977	0.2476		2	0	1.0	-34.02
c.1707T>A	F569L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none; all available predictors that provide a verdict classify the variant as pathogenic, with the exception of FoldX and Foldetta, whose results are uncertain and therefore treated as unavailable. The high‑accuracy predictors give the following: AlphaMissense‑Optimized predicts pathogenic; 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, is uncertain and thus not considered evidence. Based on the overwhelming consensus of pathogenic predictions and the lack of contrary evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-9.784	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.86	Ambiguous	0.1	2.04	Destabilizing	1.45	Ambiguous	1.28	Destabilizing	0.675	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.13	Pathogenic	0.05	Affected			0.1977	0.2476		2	0	1.0	-34.02
c.1707T>G	F569L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none; all available predictors that provide a verdict classify the variant as pathogenic, with the exception of FoldX and Foldetta, whose outputs are uncertain and therefore treated as unavailable. The high‑accuracy predictors 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, a protein‑folding stability method combining FoldX‑MD and Rosetta, is uncertain. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-9.784	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.86	Ambiguous	0.1	2.04	Destabilizing	1.45	Ambiguous	1.28	Destabilizing	0.677	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.13	Pathogenic	0.05	Affected			0.1977	0.2476		2	0	1.0	-34.02
c.1780T>A	F594I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594I is not reported in ClinVar and has no entries in gnomAD. In silico assessment shows that all evaluated pathogenicity predictors—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the substitution as pathogenic, while FoldX, Rosetta, and Foldetta provide inconclusive results. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Consequently, the overwhelming majority of predictions point to a pathogenic impact. The variant is therefore most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.271	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.93	Ambiguous	0.1	1.67	Ambiguous	1.80	Ambiguous	1.61	Destabilizing	0.935	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.91	Pathogenic	0.02	Affected			0.1694	0.1925		1	0	1.7	-34.02
c.1780T>C	F594L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX (uncertain), Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while only FoldX and Foldetta are inconclusive. In the high‑accuracy subset, AlphaMissense‑Optimized remains pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is uncertain. No tools predict a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.270	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.41	Destabilizing	1.96	Ambiguous	1.56	Destabilizing	0.940	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.98	Pathogenic	0.03	Affected			0.1790	0.2439		2	0	1.0	-34.02
c.1782C>A	F594L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX (uncertain), Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while only FoldX and Foldetta are inconclusive. In the high‑accuracy subset, AlphaMissense‑Optimized remains pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is uncertain. No tools predict a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.270	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.41	Destabilizing	1.96	Ambiguous	1.56	Destabilizing	0.893	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.98	Pathogenic	0.03	Affected			0.1790	0.2439		2	0	1.0	-34.02
c.1782C>G	F594L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity; SGM‑Consensus also indicates a likely pathogenic outcome. No tool in the dataset predicts a benign effect. Stability‑focused methods give mixed results: FoldX is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, so these do not provide decisive evidence. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Overall, the consensus of available predictions strongly suggests that F594L is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-11.270	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.41	Destabilizing	1.96	Ambiguous	1.56	Destabilizing	0.893	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.98	Pathogenic	0.03	Affected			0.1790	0.2439		2	0	1.0	-34.02
c.1789T>A	F597I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F597I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic effect. Therefore, 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	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-13.674	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	3.62	Destabilizing	0.9	2.15	Destabilizing	2.89	Destabilizing	1.45	Destabilizing	0.951	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-2.18	Pathogenic	0.01	Affected			0.2008	0.1815		1	0	1.7	-34.02
c.1789T>C	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is listed in ClinVar with an uncertain significance (ClinVar ID 3658115.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only SIFT, whereas the remaining tools—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. The high‑accuracy AlphaMissense‑Optimized score is pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for F597L, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000					Uncertain		1				-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	0.929	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			0.2232	0.2596		2	0	1.0	-34.02
c.1791C>A	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: the benign group contains only SIFT, while the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta are inconclusive, providing no definitive evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a damaging effect, SGM‑Consensus concurs with a likely pathogenic classification, and Foldetta remains uncertain. Taken together, the overwhelming majority of predictions indicate a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	0.879	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			0.2232	0.2596		2	0	1.0	-34.02
c.1791C>G	F597L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F597L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: the benign group contains only SIFT, while the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta are inconclusive, providing no definitive evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a damaging effect, SGM‑Consensus concurs with a likely pathogenic classification, and Foldetta remains uncertain. Taken together, the overwhelming majority of predictions indicate a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-10.173	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	2.12	Destabilizing	1.43	Ambiguous	1.20	Destabilizing	0.879	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-2.06	Pathogenic	0.13	Tolerated			0.2232	0.2596		2	0	1.0	-34.02
c.1822T>A	F608I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenic or likely pathogenic. The only tool with an inconclusive result is FoldX, which is listed as uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the collective evidence, 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	GAP	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-14.939	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.92	Ambiguous	0.1	2.14	Destabilizing	2.03	Destabilizing	1.24	Destabilizing	0.904	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.62	Pathogenic	0.00	Affected			0.2115	0.2361		1	0	1.7	-34.02
c.1822T>C	F608L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. FoldX and Foldetta report uncertain stability changes, but these are not considered evidence against pathogenicity. When predictions are grouped, no tool predicts a benign outcome; all available evidence supports a harmful effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (derived from the majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta remains 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	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-12.274	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.86	Ambiguous	0.2	2.59	Destabilizing	1.73	Ambiguous	1.24	Destabilizing	0.883	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.50	Pathogenic	0.01	Affected			0.2231	0.2874		2	0	1.0	-34.02
c.1824T>A	F608L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. FoldX and Foldetta report uncertain stability changes, but these are not considered evidence against pathogenicity. When predictions are grouped, no tool predicts a benign outcome; all available evidence supports a harmful effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (derived from the majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta remains 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	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-12.274	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.86	Ambiguous	0.2	2.59	Destabilizing	1.73	Ambiguous	1.24	Destabilizing	0.747	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.50	Pathogenic	0.01	Affected			0.2231	0.2874		2	0	1.0	-34.02
c.1824T>G	F608L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX‑MD (uncertain), Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while only FoldX and Foldetta are inconclusive. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta reports an uncertain stability change. No tool predicts a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-12.274	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.86	Ambiguous	0.2	2.59	Destabilizing	1.73	Ambiguous	1.24	Destabilizing	0.747	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.50	Pathogenic	0.01	Affected			0.2231	0.2874		2	0	1.0	-34.02
c.1906T>A	F636I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-14.031	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	2.96	Destabilizing	0.2	4.57	Destabilizing	3.77	Destabilizing	1.10	Destabilizing	0.501	Likely Pathogenic	-5.78	Deleterious	0.994	Probably Damaging	0.977	Probably Damaging	3.44	Benign	0.03	Affected			0.1660	0.2153		1	0	1.7	-34.02
c.1906T>C	F636L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 the Foldetta stability analysis is inconclusive. Other stability tools (FoldX, Rosetta, premPS) are uncertain. Based on the preponderance of pathogenic predictions and the consensus from high‑accuracy methods, 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-11.871	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	0.478	Likely Benign	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			0.1853	0.3024		2	0	1.0	-34.02
c.1908T>A	F636L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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 the Foldetta stability analysis is inconclusive. Other stability tools (FoldX, Rosetta, premPS) are uncertain. Based on the preponderance of pathogenic predictions and the consensus from high‑accuracy methods, 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	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-11.871	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	0.268	Likely Benign	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			0.1853	0.3024		2	0	1.0	-34.02
c.1908T>G	F636L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus confirms a Likely Pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from FoldX‑MD, Rosetta, or premPS is available to alter this view. Overall, the majority of reliable predictors indicate a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-11.871	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	0.268	Likely Benign	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			0.1853	0.3024		2	0	1.0	-34.02
c.1915T>A	F639I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F639I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FATHMM and Rosetta, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-12.548	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	4.32	Destabilizing	0.3	0.47	Likely Benign	2.40	Destabilizing	1.44	Destabilizing	0.545	Likely Pathogenic	-5.98	Deleterious	0.994	Probably Damaging	0.659	Possibly Damaging	3.08	Benign	0.01	Affected			0.2070	0.1755		1	0	1.7	-34.02
c.1915T>C	F639L 2D AIThe SynGAP1 missense variant F639L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, polyPhen2_HumVar, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta provide uncertain results. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. Based on the majority of predictions, 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	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-11.660	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.7	1.15	Ambiguous	1.64	Ambiguous	1.43	Destabilizing	0.499	Likely Benign	-5.98	Deleterious	0.994	Probably Damaging	0.380	Benign	3.12	Benign	0.03	Affected			0.2347	0.2726		2	0	1.0	-34.02
c.1917T>A	F639L 2D AIThe SynGAP1 missense variant F639L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, polyPhen2_HumVar, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta provide uncertain results. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. Based on the majority of predictions, 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	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-11.660	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.7	1.15	Ambiguous	1.64	Ambiguous	1.43	Destabilizing	0.336	Likely Benign	-5.98	Deleterious	0.994	Probably Damaging	0.380	Benign	3.12	Benign	0.03	Affected			0.2347	0.2726		2	0	1.0	-34.02
c.1917T>G	F639L 2D AIThe SynGAP1 missense variant F639L is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas a majority of tools predict pathogenicity: SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results come from Rosetta and Foldetta. High‑accuracy methods specifically show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Overall, the balance of evidence points to a pathogenic effect for F639L, 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	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-11.660	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.7	1.15	Ambiguous	1.64	Ambiguous	1.43	Destabilizing	0.336	Likely Benign	-5.98	Deleterious	0.994	Probably Damaging	0.380	Benign	3.12	Benign	0.03	Affected			0.2347	0.2726		2	0	1.0	-34.02
c.1933T>A	F645I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F645I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are given by premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) report uncertain or inconclusive outcomes. High‑accuracy assessments indicate that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the majority of evaluated predictors (five pathogenic vs four benign) lean toward a pathogenic effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for F645I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-13.055	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	1.12	Ambiguous	0.2	1.68	Ambiguous	1.40	Ambiguous	1.01	Destabilizing	0.299	Likely Benign	-4.24	Deleterious	0.190	Benign	0.019	Benign	3.44	Benign	0.04	Affected			0.1920	0.2891		1	0	1.7	-34.02
c.1933T>C	F645L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX, Rosetta, or premPS is available to alter this view. Overall, the majority of computational evidence points to a pathogenic impact for F645L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-10.624	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	1.25	Ambiguous	1.12	Ambiguous	0.99	Ambiguous	0.264	Likely Benign	-4.24	Deleterious	0.116	Benign	0.008	Benign	3.44	Benign	0.03	Affected			0.2214	0.3873		2	0	1.0	-34.02
c.1935T>A	F645L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX, Rosetta, or premPS is available to alter this view. Overall, the majority of computational evidence points to a pathogenic impact for F645L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-10.624	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	1.25	Ambiguous	1.12	Ambiguous	0.99	Ambiguous	0.159	Likely Benign	-4.24	Deleterious	0.116	Benign	0.008	Benign	3.44	Benign	0.03	Affected			0.2214	0.3873		2	0	1.0	-34.02
c.1935T>G	F645L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F645L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess sequence conservation and structural impact fall into two groups: benign predictions are made by REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM; pathogenic predictions are made by SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. No evidence from FoldX‑MD, Rosetta, or premPS is available to alter this conclusion. Overall, the majority of computational evidence points to a pathogenic impact for F645L, and this assessment is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-10.624	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	1.25	Ambiguous	1.12	Ambiguous	0.99	Ambiguous	0.159	Likely Benign	-4.24	Deleterious	0.116	Benign	0.008	Benign	3.44	Benign	0.03	Affected			0.2214	0.3873		2	0	1.0	-34.02
c.1942T>A	F648I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F648I resides in the GAP domain. ClinVar contains no entry for this change, and it is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report a pathogenic or likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also yields a pathogenic prediction. Taken together, the evidence overwhelmingly supports a pathogenic classification for F648I, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-11.912	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.49	Destabilizing	0.1	2.49	Destabilizing	2.49	Destabilizing	1.05	Destabilizing	0.472	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.04	Affected			0.1673	0.1955		1	0	1.7	-34.02
c.1942T>C	F648L 2D AISynGAP1 missense variant F648L is listed in ClinVar with an uncertain significance (ClinVar ID 3383902.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b—consistently predict pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic change. Taken together, the preponderance of evidence points to a pathogenic impact for F648L, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000					Uncertain		1				-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	0.468	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			0.1961	0.3126		2	0	1.0	-34.02
c.1944C>A	F648L 2D AIThe SynGAP1 missense variant F648L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while the remaining 12 tools—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic; and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic. Because the majority of evidence points to a deleterious impact and there is no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	0.319	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			0.1961	0.3126		2	0	1.0	-34.02
c.1944C>G	F648L 2D AIThe SynGAP1 missense variant F648L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b all indicate pathogenicity, and the SGM Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000											-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	0.319	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			0.1961	0.3126		2	0	1.0	-34.02
c.1954T>A	F652I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F652I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No prediction or stability assessment is missing or inconclusive. Based on the consensus of the available tools, 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	0.098513	Structured	0.356594	Uncertain	0.966	0.338	0.000											-12.085	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	2.15	Destabilizing	0.1	3.40	Destabilizing	2.78	Destabilizing	1.40	Destabilizing	0.574	Likely Pathogenic	-5.71	Deleterious	0.996	Probably Damaging	0.776	Possibly Damaging	3.06	Benign	0.00	Affected			0.1553	0.1955		1	0	1.7	-34.02
c.1954T>C	F652L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F652L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and FATHMM, whereas the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all indicate pathogenicity. Stability‑based assessments from FoldX and Rosetta are inconclusive, and Foldetta likewise yields an uncertain result. High‑accuracy methods give a clearer picture: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels the variant as likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F652L. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.356594	Uncertain	0.966	0.338	0.000											-9.026	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.1	1.88	Ambiguous	1.60	Ambiguous	1.35	Destabilizing	0.467	Likely Benign	-5.65	Deleterious	0.997	Probably Damaging	0.619	Possibly Damaging	3.09	Benign	0.00	Affected			0.1750	0.2926		2	0	1.0	-34.02
c.1956T>A	F652L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F652L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and FATHMM, whereas the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all indicate pathogenicity. Stability‑based assessments from FoldX and Rosetta are inconclusive, and Foldetta likewise yields an uncertain result. High‑accuracy methods give a clearer picture: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels the variant as likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F652L. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.356594	Uncertain	0.966	0.338	0.000											-9.026	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.1	1.88	Ambiguous	1.60	Ambiguous	1.35	Destabilizing	0.306	Likely Benign	-5.65	Deleterious	0.997	Probably Damaging	0.619	Possibly Damaging	3.09	Benign	0.00	Affected			0.1750	0.2926		2	0	1.0	-34.02
c.1956T>G	F652L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F652L 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 (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. FoldX and Rosetta give uncertain results, and Foldetta likewise reports an uncertain stability change. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it Likely Pathogenic, and Foldetta remaining uncertain. Overall, the preponderance of evidence from multiple pathogenic‑predicting tools and the high‑accuracy methods points to a likely pathogenic effect for F652L, with no conflict from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.356594	Uncertain	0.966	0.338	0.000											-9.026	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.1	1.88	Ambiguous	1.60	Ambiguous	1.35	Destabilizing	0.305	Likely Benign	-5.65	Deleterious	0.997	Probably Damaging	0.619	Possibly Damaging	3.09	Benign	0.00	Affected			0.1750	0.2926		2	0	1.0	-34.02
c.1987T>A	F663I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663I 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 agreement among these tools, 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	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-15.006	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.63	Destabilizing	0.1	4.51	Destabilizing	3.57	Destabilizing	1.60	Destabilizing	0.641	Likely Pathogenic	-5.99	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.06	Benign	0.00	Affected			0.1740	0.1955		1	0	1.7	-34.02
c.1987T>C	F663L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663L is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, which scores the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity, while Foldetta’s stability analysis is inconclusive and therefore unavailable. FoldX and Foldetta are treated as unavailable due to uncertain outputs. Based on the overwhelming agreement among pathogenic predictors and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-11.996	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	2.01	Destabilizing	1.46	Ambiguous	1.51	Destabilizing	0.540	Likely Pathogenic	-5.99	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.07	Benign	0.01	Affected			0.1973	0.2936		2	0	1.0	-34.02
c.1989T>A	F663L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663L 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 (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM Consensus, premPS, and Rosetta) indicate a pathogenic impact. FoldX‑MD and Rosetta‑based stability calculations are inconclusive, yielding an uncertain Foldetta result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence from consensus and high‑accuracy tools points to a pathogenic effect for F663L. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-11.996	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	2.01	Destabilizing	1.46	Ambiguous	1.51	Destabilizing	0.423	Likely Benign	-5.99	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.07	Benign	0.01	Affected			0.1973	0.2936		2	0	1.0	-34.02
c.1989T>G	F663L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663L 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 (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, and the SGM Consensus) indicate a pathogenic impact. FoldX‑MD and Rosetta give conflicting stability results, with FoldX uncertain and Rosetta pathogenic; Foldetta, which integrates both, is also uncertain. 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 F663L. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-11.996	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	2.01	Destabilizing	1.46	Ambiguous	1.51	Destabilizing	0.423	Likely Benign	-5.99	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.07	Benign	0.01	Affected			0.1973	0.2936		2	0	1.0	-34.02
c.2035T>A	F679I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM. In contrast, a majority of predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently classify the substitution as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as Likely Pathogenic. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain, and the SGM Consensus remains pathogenic. Because the uncertain results are treated as unavailable, the clear majority of predictions support pathogenicity. Thus, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for F679I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-12.620	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.62	Ambiguous	0.4	-0.27	Likely Benign	0.68	Ambiguous	0.88	Ambiguous	0.498	Likely Benign	-5.91	Deleterious	0.993	Probably Damaging	0.977	Probably Damaging	3.59	Benign	0.01	Affected			0.1725	0.2322		1	0	1.7	-34.02
c.2035T>C	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for F679L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.506	Likely Pathogenic	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2037T>A	F679L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F679L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, FATHMM, and Foldetta, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. The majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.287	Likely Benign	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2037T>G	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and premPS are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	0.287	Likely Benign	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			0.1918	0.3493		2	0	1.0	-34.02
c.2314T>A	F772I 2D AIThe SynGAP1 missense variant F772I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-2.925	Likely Benign	0.255	Likely Benign	Likely Benign										0.142	Likely Benign	-0.38	Neutral	0.845	Possibly Damaging	0.899	Possibly Damaging	4.24	Benign	0.41	Tolerated			0.1544	0.2051		1	0	1.7	-34.02
c.2314T>C	F772L 2D AIThe SynGAP1 missense variant F772L is listed in gnomAD (6‑33442472‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250								6-33442472-T-C	1	1.28e-6	-1.751	Likely Benign	0.762	Likely Pathogenic	Likely Benign										0.161	Likely Benign	-0.47	Neutral	0.508	Possibly Damaging	0.786	Possibly Damaging	4.31	Benign	1.00	Tolerated	3.64	6	0.1661	0.3033		0	2	1.0	-34.02
c.2316C>A	F772L 2D AIThe SynGAP1 missense variant F772L is catalogued in gnomAD (ID 6‑33442474‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the preponderance of evidence indicates that F772L is most likely benign, 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 Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250								6-33442474-C-A			-1.751	Likely Benign	0.762	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-0.47	Neutral	0.508	Possibly Damaging	0.786	Possibly Damaging	4.31	Benign	1.00	Tolerated	3.64	6	0.1661	0.3033		0	2	1.0	-34.02
c.2316C>G	F772L 2D AIThe SynGAP1 missense variant F772L has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability data are available, so it is treated as unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.922662	Binding	0.329	0.884	0.250											-1.751	Likely Benign	0.762	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-0.47	Neutral	0.508	Possibly Damaging	0.786	Possibly Damaging	4.31	Benign	1.00	Tolerated	3.64	6	0.1661	0.3033		0	2	1.0	-34.02
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.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.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.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.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.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.2926T>A	F976I 2D AIThe SynGAP1 missense variant F976I has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625											-4.595	Likely Benign	0.364	Ambiguous	Likely Benign										0.148	Likely Benign	-1.16	Neutral	0.666	Possibly Damaging	0.265	Benign	4.16	Benign	0.21	Tolerated			0.2790	0.2714		1	0	1.7	-34.02
c.2926T>C	F976L 2D AIThe SynGAP1 missense variant F976L 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 HumVar), SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as “Likely Benign.” In contrast, AlphaMissense‑Default predicts a pathogenic effect, while AlphaMissense‑Optimized is uncertain. No Foldetta (FoldX‑MD/ Rosetta) stability result is available, so it does not contribute to the assessment. Overall, the majority of high‑confidence predictors indicate a benign impact, and this is consistent with the lack of ClinVar evidence. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625											-2.432	Likely Benign	0.825	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-0.87	Neutral	0.264	Benign	0.102	Benign	4.20	Benign	0.53	Tolerated	4.32	2	0.2829	0.3082		2	0	1.0	-34.02
c.2928T>A	F976L 2D AIThe SynGAP1 missense variant F976L is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443480‑T‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from high‑accuracy predictors and consensus analysis indicates that F976L is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625								6-33443480-T-A	2	1.24e-6	-2.432	Likely Benign	0.825	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-0.87	Neutral	0.264	Benign	0.102	Benign	4.20	Benign	0.53	Tolerated	4.32	2	0.2829	0.3082		2	0	1.0	-34.02
c.2928T>G	F976L 2D AIThe SynGAP1 missense variant F976L is listed in ClinVar (ID 624245.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome. The high‑accuracy consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. AlphaMissense‑Optimized is inconclusive, and no Foldetta (FoldX‑MD/Rosetta stability) result is available. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar designation of uncertainty rather than a definitive pathogenic claim. Thus, the variant is most likely benign, and its predictions do not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625					Uncertain		1				-2.432	Likely Benign	0.825	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-0.87	Neutral	0.264	Benign	0.102	Benign	4.20	Benign	0.53	Tolerated	4.32	2	0.2829	0.3082		2	0	1.0	-34.02
c.2935T>A	F979I 2D AIThe SynGAP1 missense variant F979I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods reinforce the benign prediction: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta data are missing. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625											-4.053	Likely Benign	0.512	Ambiguous	Likely Benign										0.163	Likely Benign	-1.07	Neutral	0.925	Possibly Damaging	0.629	Possibly Damaging	4.19	Benign	0.06	Tolerated			0.2368	0.3009		1	0	1.7	-34.02
c.2935T>C	F979L 2D AIThe SynGAP1 missense variant F979L (ClinVar ID 1000410.0, status Uncertain, not found in gnomAD) has been evaluated by multiple in silico predictors. Benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while pathogenic predictions are reported by polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625					Uncertain		1				-2.341	Likely Benign	0.870	Likely Pathogenic	Ambiguous										0.228	Likely Benign	-1.00	Neutral	0.625	Possibly Damaging	0.430	Benign	4.22	Benign	0.73	Tolerated	4.32	2	0.2447	0.3876		2	0	1.0	-34.02
c.2937C>A	F979L 2D AIThe SynGAP1 missense variant F979L has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv and 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625											-2.341	Likely Benign	0.870	Likely Pathogenic	Ambiguous										0.328	Likely Benign	-1.00	Neutral	0.625	Possibly Damaging	0.430	Benign	4.22	Benign	0.73	Tolerated	4.32	2	0.2447	0.3876		2	0	1.0	-34.02
c.2937C>G	F979L 2D AIThe SynGAP1 missense variant F979L has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv and 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625											-2.341	Likely Benign	0.870	Likely Pathogenic	Ambiguous										0.328	Likely Benign	-1.00	Neutral	0.625	Possibly Damaging	0.430	Benign	4.22	Benign	0.73	Tolerated	4.32	2	0.2447	0.3876		2	0	1.0	-34.02
c.3028T>A	F1010I 2D AIThe SynGAP1 missense variant F1010I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-3.726	Likely Benign	0.664	Likely Pathogenic	Likely Benign										0.126	Likely Benign	-1.74	Neutral	0.980	Probably Damaging	0.783	Possibly Damaging	2.57	Benign	0.05	Affected			0.2405	0.2464		1	0	1.7	-34.02
c.3028T>C	F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized is currently uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-1.982	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.099	Likely Benign	-1.51	Neutral	0.910	Possibly Damaging	0.468	Possibly Damaging	2.75	Benign	0.62	Tolerated			0.2538	0.3245		2	0	1.0	-34.02
c.3030T>A	F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized is currently uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-1.982	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-1.51	Neutral	0.910	Possibly Damaging	0.468	Possibly Damaging	2.75	Benign	0.62	Tolerated			0.2538	0.3245		2	0	1.0	-34.02
c.3030T>G	F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign classification, and 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 evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for F1010L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-1.982	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-1.51	Neutral	0.910	Possibly Damaging	0.468	Possibly Damaging	2.75	Benign	0.62	Tolerated			0.2538	0.3245		2	0	1.0	-34.02
c.3049T>A	F1017I 2D AIThe SynGAP1 missense variant F1017I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of conventional tools (5 pathogenic vs 4 benign) lean toward pathogenicity, but the single high‑accuracy benign prediction introduces uncertainty. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625											-3.244	Likely Benign	0.584	Likely Pathogenic	Likely Benign										0.113	Likely Benign	-2.55	Deleterious	0.951	Possibly Damaging	0.710	Possibly Damaging	2.50	Benign	0.05	Affected			0.2050	0.1969		1	0	1.7	-34.02
c.3049T>C	F1017L 2D AIThe SynGAP1 missense variant F1017L is listed in ClinVar (ID 3719654.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus score (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote) is benign. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence points to a benign impact, aligning with the ClinVar classification and showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625					Benign		1				-2.048	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-2.38	Neutral	0.798	Possibly Damaging	0.373	Benign	2.65	Benign	0.72	Tolerated	3.77	5	0.2198	0.3027		0	2	1.0	-34.02
c.3051C>A	F1017L 2D AIThe SynGAP1 missense variant F1017L is catalogued in gnomAD (ID 6‑33443603‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM; pathogenic predictions come from polyPhen‑2 HumDiv 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 a likely benign outcome. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability data are available. Overall, the preponderance of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625								6-33443603-C-A			-2.048	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.140	Likely Benign	-2.38	Neutral	0.798	Possibly Damaging	0.373	Benign	2.65	Benign	0.72	Tolerated	3.77	5	0.2198	0.3027		0	2	1.0	-34.02
c.3051C>G	F1017L 2D AIThe SynGAP1 missense variant F1017L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv and 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625											-2.048	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.140	Likely Benign	-2.38	Neutral	0.798	Possibly Damaging	0.373	Benign	2.65	Benign	0.72	Tolerated	3.77	5	0.2198	0.3027		0	2	1.0	-34.02
c.376T>A	F126I 2D AIThe SynGAP1 missense variant F126I is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify it as benign. Only two tools predict pathogenicity—SIFT and AlphaMissense‑Default. High‑accuracy consensus methods reinforce the benign assessment: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and AlphaMissense‑Optimized itself predicts benign. The protein‑folding stability predictor Foldetta was not available for this variant. Overall, the majority of evidence points to a benign 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 Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-2.919	Likely Benign	0.735	Likely Pathogenic	Likely Benign										0.044	Likely Benign	-2.20	Neutral	0.160	Benign	0.045	Benign	3.95	Benign	0.00	Affected			0.2569	0.2418		1	0	1.7	-34.02
c.376T>C	F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status, which contains no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.992	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-2.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.00	Affected			0.2780	0.3399		2	0	1.0	-34.02
c.378C>A	F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status, which contains no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.992	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.114	Likely Benign	-2.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.00	Affected			0.2780	0.3399		2	0	1.0	-34.02
c.378C>G	F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact; the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.992	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.114	Likely Benign	-2.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.00	Affected			0.2780	0.3399		2	0	1.0	-34.02
c.394T>A	F132I 2D AISynGAP1 missense variant F132I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign) and Foldetta results are unavailable. Because the majority of consensus tools predict benign and no ClinVar evidence contradicts this, the variant is most likely benign, although the pathogenic signal from AlphaMissense‑Optimized and the inconclusive SGM Consensus leave some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-6.245	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-3.23	Deleterious	0.084	Benign	0.020	Benign	3.36	Benign	0.00	Affected			0.2306	0.1698		1	0	1.7	-34.02
c.394T>C	F132L 2D AIThe SynGAP1 missense variant F132L is not reported in ClinVar (status: none) but is present in gnomAD (ID 6‑33432691‑T‑C). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Overall, the majority of consensus tools lean toward a benign interpretation, and the single high‑accuracy pathogenic prediction is counterbalanced by inconclusive consensus and missing folding‑stability data. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250								6-33432691-T-C			-5.401	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.165	Likely Benign	-2.99	Deleterious	0.000	Benign	0.002	Benign	3.46	Benign	0.00	Affected	3.61	5	0.2564	0.2669		0	2	1.0	-34.02
c.396C>A	F132L 2D AIThe SynGAP1 missense variant F132L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). Foldetta, a protein‑folding‑stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools (AlphaMissense‑Optimized and AlphaMissense‑Default) both predict pathogenicity, while the consensus and stability analyses are inconclusive or missing. Overall, the majority of individual predictors and the high‑accuracy tools lean toward a pathogenic effect, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-5.401	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.137	Likely Benign	-2.99	Deleterious	0.000	Benign	0.002	Benign	3.46	Benign	0.00	Affected	3.61	5	0.2564	0.2669		0	2	1.0	-34.02
c.396C>G	F132L 2D AIThe SynGAP1 missense variant F132L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools (AlphaMissense‑Optimized and AlphaMissense‑Default) both predict pathogenicity, whereas the consensus and stability analyses are inconclusive or missing. Overall, the majority of individual predictors and the two high‑accuracy tools suggest a pathogenic effect, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-5.401	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.137	Likely Benign	-2.99	Deleterious	0.000	Benign	0.002	Benign	3.46	Benign	0.00	Affected	3.61	5	0.2564	0.2669		0	2	1.0	-34.02
c.4009T>A	F1337I 2D AIThe SynGAP1 missense variant F1337I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate a pathogenic effect. This prediction 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.			0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625											-2.761	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.252	Likely Benign	-3.32	Deleterious	0.947	Possibly Damaging	0.950	Probably Damaging	2.77	Benign	0.00	Affected			0.2574	0.2875		1	0	1.7	-34.02
c.4009T>C	F1337L 2D AIThe SynGAP1 missense variant F1337L 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 FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a likely 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.			0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625											-2.396	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.186	Likely Benign	-3.17	Deleterious	0.880	Possibly Damaging	0.899	Possibly Damaging	2.81	Benign	0.00	Affected	3.77	5	0.2765	0.3543		0	2	1.0	-34.02
c.4011C>A	F1337L 2D AIThe SynGAP1 missense variant F1337L is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451885‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. 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.			0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625								6-33451885-C-A			-2.396	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.111	Likely Benign	-3.17	Deleterious	0.880	Possibly Damaging	0.899	Possibly Damaging	2.81	Benign	0.00	Affected	3.77	5	0.2765	0.3543		0	2	1.0	-34.02
c.4011C>G	F1337L 2D AIThe SynGAP1 missense variant F1337L is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes), and Foldetta data are unavailable. With a predominance of pathogenic calls and a single high‑confidence pathogenic prediction, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for F1337L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625											-2.396	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.122	Likely Benign	-3.17	Deleterious	0.880	Possibly Damaging	0.899	Possibly Damaging	2.81	Benign	0.00	Affected	3.77	5	0.2765	0.3543		0	2	1.0	-34.02
c.466T>A	F156I 2D AIThe SynGAP1 missense variant F156I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-10.505	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.38	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.99	Benign	0.00	Affected			0.1960	0.1938		1	0	1.7	-34.02
c.466T>C	F156L 2D AIThe SynGAP1 missense variant F156L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus is ambiguous. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic										0.180	Likely Benign	-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			0.2067	0.3109		2	0	1.0	-34.02
c.468T>A	F156L 2D AIThe SynGAP1 missense variant F156L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus is ambiguous. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			0.2067	0.3109		2	0	1.0	-34.02
c.468T>G	F156L 2D AISynGAP1 missense variant F156L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (benign)—leans toward benign. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of conventional tools indicates a pathogenic effect, and the high‑accuracy predictions are mixed; no ClinVar entry exists to contradict the assessment. Therefore, 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.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic										0.163	Likely Benign	-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			0.2067	0.3109		2	0	1.0	-34.02
c.487T>A	F163I 2D AIThe SynGAP1 missense variant F163I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (five pathogenic vs. three benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-10.706	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-1.62	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	4.12	Benign	0.03	Affected			0.2114	0.2320		1	0	1.7	-34.02
c.487T>C	F163L 2D AIThe SynGAP1 missense variant F163L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this assessment does not contradict the ClinVar status, which currently has no classification for F163L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-6.380	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-1.22	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.21	Benign	0.37	Tolerated			0.2191	0.3491		2	0	1.0	-34.02
c.489C>A	F163L 2D AIThe SynGAP1 missense variant F163L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this assessment does not contradict the ClinVar status, which currently has no classification for F163L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-6.380	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.22	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.21	Benign	0.37	Tolerated			0.2191	0.3491		2	0	1.0	-34.02
c.489C>G	F163L 2D AIThe SynGAP1 missense variant F163L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, six tools favor a benign outcome versus four favoring pathogenicity, and the high‑accuracy predictions are conflicting. Thus, the variant is most likely benign based on the current consensus, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-6.380	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.22	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.21	Benign	0.37	Tolerated			0.2191	0.3491		2	0	1.0	-34.02
c.529T>A	F177I 2D AIThe SynGAP1 missense variant F177I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. three pathogenic) suggest a benign impact, though the presence of pathogenic signals from high‑accuracy tools introduces uncertainty. The variant is most likely benign based on the current evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-10.208	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.148	Likely Benign	-0.60	Neutral	0.131	Benign	0.058	Benign	4.18	Benign	0.11	Tolerated			0.2282	0.3299		1	0	1.7	-34.02
c.529T>C	F177L 2D AIThe SynGAP1 missense variant F177L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence (seven benign predictions versus two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-5.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.184	Likely Benign	0.24	Neutral	0.022	Benign	0.022	Benign	4.41	Benign	1.00	Tolerated			0.2376	0.4280		2	0	1.0	-34.02
c.531T>A	F177L 2D AIThe SynGAP1 missense variant F177L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence (seven benign predictions versus two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-5.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.173	Likely Benign	0.24	Neutral	0.022	Benign	0.022	Benign	4.41	Benign	1.00	Tolerated			0.2376	0.4280		2	0	1.0	-34.02
c.531T>G	F177L 2D AIThe SynGAP1 missense variant F177L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence (seven benign predictions versus two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-5.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.173	Likely Benign	0.24	Neutral	0.022	Benign	0.022	Benign	4.41	Benign	1.00	Tolerated			0.2376	0.4280		2	0	1.0	-34.02
c.61T>A	F21I 2D AIThe SynGAP1 missense variant F21I is listed in gnomAD (ID 6‑33420325‑T‑A) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also benign; Foldetta results are unavailable. Taken together, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420325-T-A			-3.678	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.141	Likely Benign	0.56	Neutral	0.462	Possibly Damaging	0.307	Benign	4.29	Benign	0.00	Affected	4.32	1	0.2703	0.2469		0	1	1.7	-34.02
c.61T>C	F21L 2D AIThe SynGAP1 missense variant F21L is reported in gnomAD (ID 6‑33420325‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized uncertain, SGM‑Consensus Likely Benign, and no Foldetta stability data is available. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420325-T-C			-2.480	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.140	Likely Benign	0.15	Neutral	0.140	Benign	0.153	Benign	4.34	Benign	0.00	Affected	4.32	1	0.2680	0.3250		0	2	1.0	-34.02
c.63C>A	F21L 2D AIThe SynGAP1 missense variant F21L is reported in gnomAD (ID 6‑33420327‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420327-C-A			-2.480	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.103	Likely Benign	0.15	Neutral	0.140	Benign	0.153	Benign	4.34	Benign	0.00	Affected	4.32	1	0.2680	0.3250		0	2	1.0	-34.02
c.63C>G	F21L 2D AIThe SynGAP1 missense variant F21L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while AlphaMissense‑Optimized remains uncertain and Foldetta is unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict the ClinVar status, which is currently unreported. Thus, based on the available computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500											-2.480	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.104	Likely Benign	0.15	Neutral	0.140	Benign	0.153	Benign	4.34	Benign	0.00	Affected	4.32	1	0.2680	0.3250		0	2	1.0	-34.02
c.652T>A	F218I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218I is reported in gnomAD (variant ID 6‑33435294‑T‑A) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while benign predictions are limited to polyPhen‑2 (HumVar), SIFT, and FATHMM. High‑accuracy assessments reinforce the pathogenic view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or folding 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 status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000								6-33435294-T-A	1	6.20e-7	-12.211	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	4.69	Destabilizing	0.2	5.93	Destabilizing	5.31	Destabilizing	1.18	Destabilizing	0.612	Likely Pathogenic	-3.81	Deleterious	0.510	Possibly Damaging	0.066	Benign	5.85	Benign	0.08	Tolerated	3.41	13	0.2106	0.2459		0	1	1.7	-34.02
c.652T>C	F218L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect comprise REVEL, Rosetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta provide uncertain results and are therefore considered unavailable for interpretation. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for F218L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000											-8.861	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.4	2.36	Destabilizing	1.66	Ambiguous	1.08	Destabilizing	0.546	Likely Pathogenic	-3.80	Deleterious	0.158	Benign	0.025	Benign	5.90	Benign	0.15	Tolerated			0.2331	0.3241		2	0	1.0	-34.02
c.654C>A	F218L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218L 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that agree on a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), Rosetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta are inconclusive and are treated as unavailable. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts Likely Pathogenic; Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000											-8.861	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.4	2.36	Destabilizing	1.66	Ambiguous	1.08	Destabilizing	0.477	Likely Benign	-3.80	Deleterious	0.158	Benign	0.025	Benign	5.90	Benign	0.15	Tolerated			0.2331	0.3241		2	0	1.0	-34.02
c.654C>G	F218L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218L 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that agree on a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), Rosetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Foldetta are inconclusive and are treated as unavailable. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts Likely Pathogenic; Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000											-8.861	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.4	2.36	Destabilizing	1.66	Ambiguous	1.08	Destabilizing	0.477	Likely Benign	-3.80	Deleterious	0.158	Benign	0.025	Benign	5.90	Benign	0.15	Tolerated			0.2331	0.3241		2	0	1.0	-34.02
c.658T>A	F220I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F220I 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 polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding 3 pathogenic versus 1 benign calls, thus supporting a pathogenic classification. High‑accuracy tools specifically report pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.219301	Structured	0.429422	Uncertain	0.898	0.295	0.000											-12.041	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.1	2.35	Destabilizing	2.73	Destabilizing	1.03	Destabilizing	0.921	Likely Pathogenic	-4.98	Deleterious	0.300	Benign	0.098	Benign	4.06	Benign	0.01	Affected			0.2292	0.3127		1	0	1.7	-34.02
c.658T>C	F220L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F220L 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 polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—indicate a pathogenic effect. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic, 1 benign), thus supporting a pathogenic classification. High‑accuracy assessments further corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.219301	Structured	0.429422	Uncertain	0.898	0.295	0.000											-9.601	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.08	Destabilizing	0.1	2.24	Destabilizing	2.16	Destabilizing	1.33	Destabilizing	0.850	Likely Pathogenic	-4.95	Deleterious	0.003	Benign	0.005	Benign	4.24	Benign	0.02	Affected			0.2589	0.4108		2	0	1.0	-34.02
c.660T>A	F220L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F220L 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 polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—indicate a pathogenic effect. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic, 1 benign), thus supporting a pathogenic classification. High‑accuracy assessments further corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.219301	Structured	0.429422	Uncertain	0.898	0.295	0.000											-9.601	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.08	Destabilizing	0.1	2.24	Destabilizing	2.16	Destabilizing	1.33	Destabilizing	0.752	Likely Pathogenic	-4.95	Deleterious	0.003	Benign	0.005	Benign	4.24	Benign	0.02	Affected			0.2589	0.4108		2	0	1.0	-34.02
c.660T>G	F220L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F220L 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 polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—indicate a pathogenic effect. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic, 1 benign), thus supporting a pathogenic classification. High‑accuracy assessments further corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.219301	Structured	0.429422	Uncertain	0.898	0.295	0.000											-9.601	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.08	Destabilizing	0.1	2.24	Destabilizing	2.16	Destabilizing	1.33	Destabilizing	0.752	Likely Pathogenic	-4.95	Deleterious	0.003	Benign	0.005	Benign	4.24	Benign	0.02	Affected			0.2589	0.4108		2	0	1.0	-34.02
c.691T>A	F231I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include polyPhen‑2 HumVar and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, while Foldetta’s stability prediction is uncertain and thus not considered evidence. No other tools provide definitive pathogenic or benign conclusions. Based on the preponderance of pathogenic predictions and the lack of contrary evidence, 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	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000											-13.827	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.4	1.65	Ambiguous	1.41	Ambiguous	0.94	Ambiguous	0.894	Likely Pathogenic	-5.01	Deleterious	0.759	Possibly Damaging	0.328	Benign	5.76	Benign	0.00	Affected			0.2122	0.2813		1	0	1.7	-34.02
c.691T>C	F231L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact for F231L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000											-9.482	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.3	1.26	Ambiguous	1.17	Ambiguous	0.85	Ambiguous	0.801	Likely Pathogenic	-5.08	Deleterious	0.390	Benign	0.142	Benign	6.04	Benign	0.01	Affected			0.2338	0.3794		2	0	1.0	-34.02
c.693T>A	F231L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a pathogenic impact for F231L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000											-9.482	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.3	1.26	Ambiguous	1.17	Ambiguous	0.85	Ambiguous	0.662	Likely Pathogenic	-5.08	Deleterious	0.390	Benign	0.142	Benign	6.04	Benign	0.01	Affected			0.2338	0.3794		2	0	1.0	-34.02
c.693T>G	F231L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar and FATHMM, whereas REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized all predict a pathogenic effect. The SGM‑Consensus score is labeled Likely Pathogenic, and the remaining tools (FoldX, Rosetta, Foldetta, premPS) are inconclusive. High‑accuracy methods give a pathogenic verdict from AlphaMissense‑Optimized, a Likely Pathogenic result from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and an uncertain outcome from Foldetta. Overall, the majority of evidence points to a pathogenic impact for F231L, 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	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000											-9.482	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.3	1.26	Ambiguous	1.17	Ambiguous	0.85	Ambiguous	0.661	Likely Pathogenic	-5.08	Deleterious	0.390	Benign	0.142	Benign	6.04	Benign	0.01	Affected			0.2338	0.3794		2	0	1.0	-34.02
c.919T>A	F307I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307I 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 are FoldX, Rosetta, and Foldetta. Tools that predict it as pathogenic include SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments give AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Benign. Overall, the majority of predictions (10/13) indicate pathogenicity, while only three tools suggest benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-13.114	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.49	Likely Benign	0.2	0.19	Likely Benign	0.34	Likely Benign	0.61	Ambiguous	0.632	Likely Pathogenic	-5.52	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.06	Pathogenic	0.01	Affected			0.2531	0.3036		1	0	1.7	-34.02
c.919T>C	F307L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized and the SGM Consensus both indicate a likely pathogenic effect, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the bulk of evidence points to a pathogenic impact, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-10.173	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	0.14	Likely Benign	0.34	Likely Benign	0.57	Ambiguous	0.597	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.01	Affected			0.2800	0.4207		2	0	1.0	-34.02
c.921C>A	F307L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized and the SGM Consensus both indicate a likely pathogenic effect, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the bulk of evidence points to a pathogenic impact, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-10.173	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	0.14	Likely Benign	0.34	Likely Benign	0.57	Ambiguous	0.529	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.01	Affected			0.2800	0.4207		2	0	1.0	-34.02
c.921C>G	F307L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F307L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta and Foldetta, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the change as pathogenic. Uncertain results are reported by FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the consensus of the majority of tools points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.298791	Structured	0.327302	Uncertain	0.900	0.315	0.125											-10.173	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	0.14	Likely Benign	0.34	Likely Benign	0.57	Ambiguous	0.529	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.01	Affected			0.2800	0.4207		2	0	1.0	-34.02
c.934T>A	F312I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312I is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-12.000	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.09	Destabilizing	0.3	3.10	Destabilizing	2.60	Destabilizing	1.72	Destabilizing	0.872	Likely Pathogenic	-5.52	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.23	Pathogenic	0.01	Affected			0.1997	0.2842		1	0	1.7	-34.02
c.934T>C	F312L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” The only tool with an inconclusive result is FoldX, which is listed as “Uncertain.” No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective 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	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-9.891	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.3	2.91	Destabilizing	2.04	Destabilizing	1.27	Destabilizing	0.852	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.32	Pathogenic	0.05	Affected			0.2149	0.3813		2	0	1.0	-34.02
c.936C>A	F312L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” The only tool with an inconclusive result is FoldX, which is listed as “Uncertain.” No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective 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	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-9.891	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.3	2.91	Destabilizing	2.04	Destabilizing	1.27	Destabilizing	0.615	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.32	Pathogenic	0.05	Affected			0.2149	0.3813		2	0	1.0	-34.02
c.936C>G	F312L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” The only tool with an inconclusive result is FoldX, which is listed as “Uncertain.” No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective 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	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-9.891	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.3	2.91	Destabilizing	2.04	Destabilizing	1.27	Destabilizing	0.615	Likely Pathogenic	-5.52	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.32	Pathogenic	0.05	Affected			0.2149	0.3813		2	0	1.0	-34.02
c.940T>A	F314I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a pathogenic effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict deleterious or pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Tools with uncertain or inconclusive results include Rosetta, Foldetta, and ESM1b. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, while Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation (i.e., no benign classification). Therefore, the variant is most likely pathogenic, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-7.059	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	2.23	Destabilizing	0.4	1.08	Ambiguous	1.66	Ambiguous	1.31	Destabilizing	0.534	Likely Pathogenic	-4.98	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.26	Pathogenic	0.01	Affected			0.2052	0.2308		1	0	1.7	-34.02
c.940T>C	F314L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314L is not 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: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable evidence. 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 remains uncertain. Overall, the preponderance of evidence indicates that F314L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-6.004	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic	0.87	Ambiguous	0.1	0.82	Ambiguous	0.85	Ambiguous	1.21	Destabilizing	0.476	Likely Benign	-4.85	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.30	Pathogenic	0.05	Affected			0.2204	0.3089		2	0	1.0	-34.02
c.942T>A	F314L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314L is not 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: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable evidence. 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 remains uncertain. Overall, the preponderance of evidence indicates that F314L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-6.004	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic	0.87	Ambiguous	0.1	0.82	Ambiguous	0.85	Ambiguous	1.21	Destabilizing	0.336	Likely Benign	-4.85	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.30	Pathogenic	0.05	Affected			0.2204	0.3089		2	0	1.0	-34.02
c.942T>G	F314L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314L is not 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: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable evidence. 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 remains uncertain. Overall, the preponderance of evidence indicates that F314L is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125											-6.004	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic	0.87	Ambiguous	0.1	0.82	Ambiguous	0.85	Ambiguous	1.21	Destabilizing	0.336	Likely Benign	-4.85	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.30	Pathogenic	0.05	Affected			0.2204	0.3089		2	0	1.0	-34.02
c.1129A>G	M377V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377V is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (gnomAD ID 6‑33438034‑A‑G). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from FoldX, Rosetta, and Foldetta, which are treated as unavailable. High‑accuracy assessments confirm the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, while Foldetta remains uncertain. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.675549	Disordered	0.431183	Uncertain	0.324	0.884	0.625								6-33438034-A-G			-1.507	Likely Benign	0.073	Likely Benign	Likely Benign	0.92	Ambiguous	0.3	1.27	Ambiguous	1.10	Ambiguous	0.48	Likely Benign	0.161	Likely Benign	-0.31	Neutral	0.000	Benign	0.000	Benign	5.46	Benign	0.15	Tolerated	4.32	12	0.4530	0.4096		1	2	2.3	-32.06
c.1225A>G	M409V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409V is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors indicates a benign effect: REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports likely benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenicity. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote) is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, reports benign. No conflicting evidence is present. Therefore, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000											-4.109	Likely Benign	0.123	Likely Benign	Likely Benign	1.13	Ambiguous	0.2	-0.25	Likely Benign	0.44	Likely Benign	0.37	Likely Benign	0.163	Likely Benign	-0.76	Neutral	0.996	Probably Damaging	0.974	Probably Damaging	4.26	Benign	1.00	Tolerated			0.2706	0.4286		2	1	2.3	-32.06
c.1240A>G	M414V 2D AISynGAP1 M414V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; the remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. The SGM consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic majority. High‑accuracy assessments give AlphaMissense‑Optimized benign, SGM consensus pathogenic, and Foldetta uncertain. Because the high‑accuracy predictions are divided and the overall tool set is evenly split, there is no definitive evidence for pathogenicity or benignity. Thus, the variant is most likely inconclusive, and this lack of consensus does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000					Uncertain		1				-8.003	Likely Pathogenic	0.541	Ambiguous	Likely Benign	1.81	Ambiguous	0.4	1.73	Ambiguous	1.77	Ambiguous	0.95	Ambiguous	0.261	Likely Benign	-2.95	Deleterious	0.999	Probably Damaging	0.987	Probably Damaging	3.43	Benign	0.24	Tolerated			0.2585	0.3482		2	1	2.3	-32.06
c.1288A>G	M430V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated changes. Only polyPhen‑2 HumDiv flags it as pathogenic, while the SGM‑Consensus score is Likely Benign. Stability‑based methods are inconclusive: FoldX and premPS return Uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports Uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta remains Uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000											-3.555	Likely Benign	0.091	Likely Benign	Likely Benign	1.48	Ambiguous	0.1	-0.23	Likely Benign	0.63	Ambiguous	0.87	Ambiguous	0.103	Likely Benign	-1.35	Neutral	0.918	Possibly Damaging	0.185	Benign	3.53	Benign	0.51	Tolerated			0.3397	0.4953		2	1	2.3	-32.06
c.1402A>G	M468V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M468V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from PROVEAN, SIFT, and AlphaMissense‑Optimized, while pathogenic predictions are made by REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools, premPS and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments further clarify the variant’s impact: AlphaMissense‑Optimized predicts a benign effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also classifies the variant as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.284882	Structured	0.339253	Uncertain	0.932	0.257	0.000					Uncertain		1				-9.461	Likely Pathogenic	0.361	Ambiguous	Likely Benign	2.69	Destabilizing	0.1	2.20	Destabilizing	2.45	Destabilizing	0.89	Ambiguous	0.570	Likely Pathogenic	-1.66	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	-1.21	Pathogenic	0.08	Tolerated	3.37	31	0.3309	0.3845		1	2	2.3	-32.06
c.1408A>G	M470V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M470V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Consensus from most in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all score it as deleterious. Only two tools—SIFT and AlphaMissense‑Optimized—classify it as benign, while Rosetta and AlphaMissense‑Default remain inconclusive. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized reports a benign outcome, but the SGM‑Consensus (derived from a majority of pathogenic calls among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining pathogenic FoldX with uncertain Rosetta) both predict pathogenicity. Overall, the preponderance of evidence supports a likely pathogenic classification, which does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.351497	Uncertain	0.908	0.272	0.000					Uncertain		1				-8.856	Likely Pathogenic	0.478	Ambiguous	Likely Benign	2.73	Destabilizing	0.1	1.88	Ambiguous	2.31	Destabilizing	1.31	Destabilizing	0.770	Likely Pathogenic	-3.58	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.20	Pathogenic	0.15	Tolerated	3.37	34	0.2710	0.3256		1	2	2.3	-32.06
c.1429A>G	M477V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477V is listed in ClinVar with no submitted interpretation and is present in the gnomAD database (variant ID 6‑33438461‑A‑G). Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict benign or likely benign. Only two tools predict a pathogenic outcome: polyPhen2_HumDiv and FATHMM. Predictions from FoldX and Foldetta are uncertain. High‑accuracy methods reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, while Foldetta remains inconclusive. Taken together, the majority of evidence supports a benign classification for M477V, and this assessment does not contradict the ClinVar status, which currently has no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000								6-33438461-A-G	1	6.20e-7	-3.995	Likely Benign	0.127	Likely Benign	Likely Benign	1.64	Ambiguous	0.3	0.42	Likely Benign	1.03	Ambiguous	0.24	Likely Benign	0.209	Likely Benign	-1.04	Neutral	0.716	Possibly Damaging	0.204	Benign	-1.19	Pathogenic	0.22	Tolerated	3.37	34	0.3093	0.3445		1	2	2.3	-32.06																10.1016/j.ajhg.2020.11.011
c.1492A>G	M498V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M498V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic (FoldX, Foldetta, premPS, polyPhen‑2 HumDiv, SIFT, FATHMM). Rosetta is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta predicts a pathogenic effect on protein stability. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.399612	Uncertain	0.932	0.158	0.000											-3.229	Likely Benign	0.317	Likely Benign	Likely Benign	2.74	Destabilizing	0.1	1.26	Ambiguous	2.00	Destabilizing	1.17	Destabilizing	0.483	Likely Benign	-1.82	Neutral	0.752	Possibly Damaging	0.279	Benign	-1.28	Pathogenic	0.04	Affected			0.2737	0.2737		2	1	2.3	-32.06
c.1633A>G	M545V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545V is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include SIFT and Rosetta, while a majority of tools predict a pathogenic outcome: PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Tools with inconclusive results (FoldX, Foldetta, premPS, ESM1b) are considered unavailable for interpretation. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for M545V. 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	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000											-7.481	In-Between	0.979	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	0.33	Likely Benign	0.62	Ambiguous	0.94	Ambiguous	0.688	Likely Pathogenic	-3.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.26	Pathogenic	0.34	Tolerated			0.2454	0.2953		2	1	2.3	-32.06
c.172A>G	M58V 2D AIThe SynGAP1 missense variant M58V is listed in ClinVar (ID 2962156.0) with an uncertain significance status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus from AlphaMissense‑Optimized, SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta (protein‑folding stability) is available only for the first two; Foldetta data are missing. The SGM Consensus, based on a majority of benign predictions, indicates a likely benign outcome. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000					Uncertain		1				-2.211	Likely Benign	0.688	Likely Pathogenic	Likely Benign										0.160	Likely Benign	-0.71	Neutral	0.006	Benign	0.091	Benign	4.19	Benign	0.00	Affected	4.32	1	0.2951	0.3917		1	2	2.3	-32.06
c.1807A>G	M603V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M603V is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS and SIFT, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic, and AlphaMissense‑Optimized is uncertain; Foldetta also remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for M603V. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-10.442	Likely Pathogenic	0.800	Likely Pathogenic	Ambiguous	1.34	Ambiguous	0.2	0.62	Ambiguous	0.98	Ambiguous	-0.15	Likely Benign	0.668	Likely Pathogenic	-3.48	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-0.92	Pathogenic	0.09	Tolerated			0.2698	0.2601		2	1	2.3	-32.06
c.1831A>G	M611V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M611V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields an inconclusive result (two benign, two pathogenic). Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports an uncertain effect, so its result is treated as unavailable. Overall, the balance of evidence leans toward a benign impact, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.236433	Structured	0.210791	Uncertain	0.870	0.253	0.000											-8.057	Likely Pathogenic	0.176	Likely Benign	Likely Benign	1.42	Ambiguous	0.4	1.56	Ambiguous	1.49	Ambiguous	0.66	Ambiguous	0.315	Likely Benign	-2.06	Neutral	0.960	Probably Damaging	0.474	Possibly Damaging	-1.04	Pathogenic	0.49	Tolerated			0.2324	0.2721		2	1	2.3	-32.06
c.1945A>G	M649V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M649V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. With 8 pathogenic versus 3 benign predictions, the overall evidence favors a deleterious effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-9.907	Likely Pathogenic	0.887	Likely Pathogenic	Ambiguous	2.84	Destabilizing	0.3	2.55	Destabilizing	2.70	Destabilizing	1.05	Destabilizing	0.370	Likely Benign	-3.99	Deleterious	0.997	Probably Damaging	0.735	Possibly Damaging	3.40	Benign	0.06	Tolerated			0.2389	0.3121		2	1	2.3	-32.06
c.1978A>G	M660V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into three groups: benign predictions come from REVEL, SIFT, and FATHMM; pathogenic predictions arise from SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; the remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evaluated predictors lean toward a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status is available. Thus, based on the current computational evidence, the M660V variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000											-11.006	Likely Pathogenic	0.836	Likely Pathogenic	Ambiguous	1.83	Ambiguous	0.1	0.77	Ambiguous	1.30	Ambiguous	1.05	Destabilizing	0.419	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.927	Probably Damaging	3.56	Benign	0.13	Tolerated			0.2614	0.2937		2	1	2.3	-32.06
c.2263A>G	M755V 2D AIThe SynGAP1 missense variant M755V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this conclusion 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 Benign		0.490133	Structured	0.783855	Binding	0.336	0.873	0.375											-3.804	Likely Benign	0.095	Likely Benign	Likely Benign										0.045	Likely Benign	-0.80	Neutral	0.002	Benign	0.003	Benign	2.73	Benign	0.27	Tolerated			0.2809	0.2873		2	1	2.3	-32.06
c.2275A>G	M759V 2D AIThe SynGAP1 missense variant M759V is catalogued in gnomAD (ID 6‑33441740‑A‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available for this variant. Taken together, the computational evidence overwhelmingly supports a benign effect, and this conclusion does not conflict with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375								6-33441740-A-G	20	1.24e-5	-3.985	Likely Benign	0.074	Likely Benign	Likely Benign										0.030	Likely Benign	-1.00	Neutral	0.267	Benign	0.127	Benign	2.67	Benign	0.23	Tolerated	3.99	5	0.2926	0.3041		1	2	2.3	-32.06																10.1016/j.ajhg.2020.11.011
c.2278A>G	M760V 2D AIThe SynGAP1 missense variant M760V is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.893402	Binding	0.346	0.865	0.375											-2.803	Likely Benign	0.109	Likely Benign	Likely Benign										0.085	Likely Benign	-1.20	Neutral	0.001	Benign	0.008	Benign	2.69	Benign	0.22	Tolerated			0.3974	0.4381		2	1	2.3	-32.06
c.2317A>G	M773V 2D AIThe SynGAP1 missense variant M773V has no ClinVar entry and is not reported in gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence indicates that M773V is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-4.353	Likely Benign	0.126	Likely Benign	Likely Benign										0.234	Likely Benign	-0.70	Neutral	0.038	Benign	0.284	Benign	4.30	Benign	0.87	Tolerated			0.3145	0.3081		2	1	2.3	-32.06
c.2341A>G	M781V 2D AIThe SynGAP1 missense variant M781V is catalogued in gnomAD (ID 6‑33442893‑A‑G) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool examined—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No pathogenic predictions are reported. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the evidence overwhelmingly supports a benign effect, and this conclusion does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625								6-33442893-A-G	4	2.48e-6	-2.624	Likely Benign	0.068	Likely Benign	Likely Benign										0.174	Likely Benign	0.00	Neutral	0.000	Benign	0.001	Benign	3.03	Benign	0.90	Tolerated	3.64	6	0.3081	0.2705		1	2	2.3	-32.06
c.2347A>G	M783V 2D AIThe SynGAP1 missense variant M783V is catalogued in gnomAD (ID 6‑33442899‑A‑G) and has no ClinVar entry. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta results are unavailable. Consequently, the variant is most likely benign, and this prediction does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625								6-33442899-A-G	1	6.21e-7	-3.453	Likely Benign	0.086	Likely Benign	Likely Benign										0.065	Likely Benign	-0.96	Neutral	0.072	Benign	0.026	Benign	2.85	Benign	0.12	Tolerated	3.64	6	0.3444	0.3710		1	2	2.3	-32.06
c.2500A>G	M834V 2D AIThe SynGAP1 missense variant M834V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.585406	Disordered	0.640801	Binding	0.258	0.863	0.375											-2.345	Likely Benign	0.074	Likely Benign	Likely Benign										0.059	Likely Benign	-1.10	Neutral	0.001	Benign	0.001	Benign	2.53	Benign	0.00	Affected			0.2562	0.2705		2	1	2.3	-32.06
c.2527A>G	M843V 2D AIThe SynGAP1 missense variant M843V 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, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus (majority vote) also as Benign; Foldetta results are unavailable. Based on the overall distribution of predictions and the high‑accuracy consensus, the variant is most likely benign, 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 Benign		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-5.171	Likely Benign	0.625	Likely Pathogenic	Likely Benign										0.246	Likely Benign	-2.12	Neutral	0.843	Possibly Damaging	0.926	Probably Damaging	2.67	Benign	0.01	Affected			0.3347	0.3630		2	1	2.3	-32.06
c.2710A>G	M904V 2D AIThe SynGAP1 missense variant M904V is reported in ClinVar (ID 833650.0) as benign and is present in gnomAD (variant ID 6‑33443262‑A‑G). All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the computational evidence strongly supports a benign classification, which aligns with the ClinVar status and shows no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.589073	Binding	0.350	0.920	0.250					Likely Benign		2	6-33443262-A-G	77	4.78e-5	-2.907	Likely Benign	0.112	Likely Benign	Likely Benign										0.058	Likely Benign	-0.33	Neutral	0.039	Benign	0.023	Benign	2.80	Benign	0.10	Tolerated	3.77	5	0.3724	0.3948		2	1	2.3	-32.06
c.2725A>G	M909V 2D AIThe SynGAP1 missense variant M909V is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250											-2.906	Likely Benign	0.230	Likely Benign	Likely Benign										0.164	Likely Benign	-0.88	Neutral	0.288	Benign	0.147	Benign	2.97	Benign	0.45	Tolerated			0.3295	0.3600		2	1	2.3	-32.06
c.2800A>G	M934V 2D AIThe SynGAP1 missense variant M934V is listed in gnomAD (ID 6‑33443352‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. Only FATHMM predicts a pathogenic outcome, representing a single dissenting signal. High‑accuracy assessments confirm the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that M934V is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625								6-33443352-A-G	1	6.20e-7	-3.286	Likely Benign	0.218	Likely Benign	Likely Benign										0.119	Likely Benign	-2.06	Neutral	0.166	Benign	0.101	Benign	2.47	Pathogenic	0.39	Tolerated	3.77	5	0.3464	0.3276		1	2	2.3	-32.06
c.3091A>G	M1031V 2D AIThe SynGAP1 missense variant M1031V is catalogued in gnomAD (ID 6‑33443643‑A‑G) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently scores the variant as benign. No pathogenic predictions are reported. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the uniform benign predictions and the lack of any ClinVar pathogenic classification, the variant is most likely benign and does not contradict existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995959	Binding	0.340	0.736	0.500								6-33443643-A-G	7	4.34e-6	-2.815	Likely Benign	0.198	Likely Benign	Likely Benign										0.054	Likely Benign	-0.81	Neutral	0.002	Benign	0.003	Benign	2.72	Benign	0.44	Tolerated	3.77	5	0.2305	0.3388		1	2	2.3	-32.06
c.3442A>G	M1148V 2D AIThe SynGAP1 missense variant M1148V is catalogued in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33444477‑A‑G). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of available predictions indicates that M1148V is most likely benign, and this conclusion does not contradict any ClinVar status, as no pathogenic claim has been reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.774279	Binding	0.343	0.835	0.875								6-33444477-A-G	3	1.86e-6	-2.358	Likely Benign	0.081	Likely Benign	Likely Benign										0.057	Likely Benign	-1.47	Neutral	0.016	Benign	0.026	Benign	2.59	Benign	0.00	Affected	4.32	2	0.3154	0.3371		1	2	2.3	-32.06
c.3481A>G	M1161V 2D AISynGAP1 missense variant M1161V is not reported in ClinVar and is present in gnomAD (ID 6‑33444516‑A‑G). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, and ESM1b; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Consequently, the evidence does not favor either outcome. The variant is most likely neither clearly benign nor pathogenic based on current predictions, and this lack of consensus does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.580690	Disordered	0.864109	Binding	0.372	0.830	0.375								6-33444516-A-G	2	1.24e-6	-3.060	Likely Benign	0.915	Likely Pathogenic	Ambiguous										0.150	Likely Benign	-1.85	Neutral	0.843	Possibly Damaging	0.926	Probably Damaging	2.27	Pathogenic	0.22	Tolerated	3.77	5	0.3422	0.3292		1	2	2.3	-32.06
c.352A>G	M118V 2D AIThe SynGAP1 missense variant M118V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-2.322	Likely Benign	0.122	Likely Benign	Likely Benign										0.158	Likely Benign	-1.23	Neutral	0.012	Benign	0.011	Benign	3.98	Benign	0.02	Affected			0.3326	0.3630		2	1	2.3	-32.06
c.3559A>G	M1187V 2D AIThe M1187V missense change in SynGAP1’s coiled‑coil domain is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.562014	Disordered	0.499801	Uncertain	0.597	0.636	0.625											-3.107	Likely Benign	0.733	Likely Pathogenic	Likely Benign										0.478	Likely Benign	-1.44	Neutral	0.843	Possibly Damaging	0.926	Probably Damaging	5.49	Benign	0.19	Tolerated			0.3300	0.2800		2	1	2.3	-32.06
c.3631A>G	M1211V 2D AIThe SynGAP1 missense variant M1211V is listed in ClinVar as Benign (ClinVar ID 3674914.0) and is present in gnomAD (ID 6‑33446623‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500					Benign		1	6-33446623-A-G	3	1.86e-6	-2.101	Likely Benign	0.258	Likely Benign	Likely Benign										0.412	Likely Benign	-0.29	Neutral	0.932	Possibly Damaging	0.949	Probably Damaging	5.43	Benign	0.72	Tolerated	3.77	5	0.2676	0.2720		1	2	2.3	-32.06
c.3703A>G	M1235V 2D AIThe SynGAP1 missense variant M1235V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. Only SIFT predicts a damaging effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this residue. Taken together, the preponderance of evidence indicates that M1235V is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125											-3.870	Likely Benign	0.099	Likely Benign	Likely Benign										0.055	Likely Benign	-1.54	Neutral	0.139	Benign	0.038	Benign	2.69	Benign	0.02	Affected			0.3048	0.3120		2	1	2.3	-32.06
c.3799A>G	M1267V 2D AIThe SynGAP1 missense variant M1267V is not 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 agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (five pathogenic vs. three benign) indicate a pathogenic effect. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Thus, based on current computational evidence, the M1267V variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-2.249	Likely Benign	0.537	Ambiguous	Likely Benign										0.254	Likely Benign	-3.34	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.35	Pathogenic	0.00	Affected			0.3057	0.3241		2	1	2.3	-32.06
c.3838A>G	M1280V 2D AIThe SynGAP1 missense variant M1280V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for M1280V, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-2.414	Likely Benign	0.063	Likely Benign	Likely Benign										0.240	Likely Benign	-2.24	Neutral	0.004	Benign	0.008	Benign	2.36	Pathogenic	0.00	Affected			0.2568	0.3137		2	1	2.3	-32.06
c.46A>G	M16V 2D AIThe SynGAP1 missense variant M16V is reported in gnomAD (ID 6‑33420310‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for M16V, and this conclusion does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375								6-33420310-A-G	16	1.05e-5	-1.595	Likely Benign	0.128	Likely Benign	Likely Benign										0.073	Likely Benign	-0.07	Neutral	0.000	Benign	0.000	Benign	4.30	Benign	0.00	Affected	4.32	1	0.3561	0.3937		1	2	2.3	-32.06
c.520A>G	M174V 2D AIThe SynGAP1 missense variant M174V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID: 6‑33435162‑A‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM; pathogenic predictions come from SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability data are available. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a 2‑vs‑2 split and is therefore inconclusive. With five benign versus three pathogenic calls and no contradictory ClinVar evidence, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375								6-33435162-A-G	2	1.24e-6	-8.604	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous										0.108	Likely Benign	-1.76	Neutral	0.213	Benign	0.067	Benign	4.12	Benign	0.04	Affected	3.61	5	0.2866	0.3841		1	2	2.3	-32.06
c.85A>G	M29V 2D AIThe SynGAP1 missense variant M29V is reported in gnomAD (ID 6‑33423494‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, representing the sole discordant signal. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for M29V, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250								6-33423494-A-G	1	6.20e-7	-1.841	Likely Benign	0.057	Likely Benign	Likely Benign										0.209	Likely Benign	-0.39	Neutral	0.006	Benign	0.091	Benign	4.27	Benign	0.00	Affected	4.32	1	0.4022	0.4433		1	2	2.3	-32.06
c.865A>G	M289V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M289V is reported in ClinVar as Benign (ClinVar ID 2122760.0) and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus all predict benign, while only FATHMM predicts pathogenic. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also indicates benign. No prediction or stability result is inconclusive. Overall, the computational evidence strongly supports a benign classification, consistent with the ClinVar status and showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000					Benign		1				-4.239	Likely Benign	0.117	Likely Benign	Likely Benign	1.09	Ambiguous	0.1	-0.27	Likely Benign	0.41	Likely Benign	0.24	Likely Benign	0.150	Likely Benign	-0.36	Neutral	0.136	Benign	0.054	Benign	1.80	Pathogenic	1.00	Tolerated	3.38	23	0.2280	0.2808		2	1	2.3	-32.06	204.2	51.0	0.0	0.0	0.2	0.0						X		Potentially Benign	The hydrophobic residue Met289, located in a β hairpin linking two anti-parallel β sheet strands (res. Met289-Arg299, res. Arg272-Leu286), is swapped for another hydrophobic residue, valine. In the variant simulations, the branched hydrocarbon side chain of Val289 packs against the phenol group of the Tyr291 side chain but is unable to form methionine-aromatic interactions. β hairpins are potential nucleation sites during the initial stages of protein folding, so even minor changes in them could be significant. However, based on the simulations, the residue swap does not cause adverse effects on the structure.
c.1082A>C	Q361P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361P is listed in ClinVar as Pathogenic (ClinVar ID 3235087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and premPS. All other evaluated algorithms—FoldX, Rosetta, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy methods specifically give a pathogenic verdict: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Based on the overwhelming agreement of these predictions, the variant is most likely pathogenic, which is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250					Likely Pathogenic		1				-13.280	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	3.12	Destabilizing	0.0	3.45	Destabilizing	3.29	Destabilizing	0.38	Likely Benign	0.482	Likely Benign	-3.03	Deleterious	0.996	Probably Damaging	0.979	Probably Damaging	1.63	Pathogenic	0.05	Affected	3.37	25	0.1986	0.5151		-1	0	1.9	-31.01
c.1220A>C	Q407P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; premPS is uncertain and is not counted. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the consensus of these predictions, 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	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-13.578	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.04	Destabilizing	0.5	2.07	Destabilizing	2.56	Destabilizing	0.88	Ambiguous	0.515	Likely Pathogenic	-5.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.88	Benign	0.02	Affected			0.1786	0.4352		0	-1	1.9	-31.01
c.1367A>C	Q456P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q456P is listed in ClinVar with an uncertain significance (ClinVar ID 2697090.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. High‑accuracy methods specifically report pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000					Uncertain		1				-15.250	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.68	Destabilizing	0.2	8.43	Destabilizing	6.06	Destabilizing	0.82	Ambiguous	0.469	Likely Benign	-5.66	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.34	Benign	0.07	Tolerated	3.37	34	0.2256	0.3631		-1	0	1.9	-31.01
c.1508A>C	Q503P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q503P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; the remaining tools (FoldX, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenic. Because the majority of evidence points to a deleterious effect, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.322935	Uncertain	0.848	0.168	0.000											-10.915	Likely Pathogenic	0.414	Ambiguous	Likely Benign	1.06	Ambiguous	0.7	5.94	Destabilizing	3.50	Destabilizing	0.75	Ambiguous	0.860	Likely Pathogenic	-5.20	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	-1.53	Pathogenic	0.03	Affected			0.2076	0.3610		0	-1	1.9	-31.01
c.1619A>C	Q540P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic, while premPS is uncertain. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a pathogenic effect. No tool predicts a benign outcome. Consequently, 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	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000											-16.096	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.95	Destabilizing	0.3	10.06	Destabilizing	7.01	Destabilizing	0.73	Ambiguous	0.922	Likely Pathogenic	-5.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.32	Pathogenic	0.01	Affected			0.1882	0.3654		0	-1	1.9	-31.01
c.164A>C	Q55P 2D AIThe SynGAP1 missense variant Q55P is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33423573‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs two benign), and Foldetta results are unavailable. Overall, more tools predict pathogenicity than benignity, and no ClinVar entry contradicts this assessment. Therefore, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000								6-33423573-A-C	1	6.20e-7	-13.163	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous										0.260	Likely Benign	-2.06	Neutral	0.462	Possibly Damaging	0.480	Possibly Damaging	3.83	Benign	0.00	Affected	4.32	1	0.2557	0.5508		-1	0	1.9	-31.01
c.1835A>C	Q612P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q612P is listed in ClinVar (ID 3660462.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, PolyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, PROVEAN, and the SGM Consensus score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). The high‑accuracy AlphaMissense‑Optimized predicts benign, whereas the SGM Consensus predicts likely pathogenic; Foldetta, a folding‑stability method combining FoldX‑MD and Rosetta outputs, returns an uncertain result and is therefore not factored into the consensus. Overall, the majority of evidence supports a pathogenic effect, which contrasts with the ClinVar uncertain classification. Thus, based on current predictions, 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	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000					Uncertain		1				-9.684	Likely Pathogenic	0.673	Likely Pathogenic	Likely Benign	-0.19	Likely Benign	0.3	3.06	Destabilizing	1.44	Ambiguous	0.56	Ambiguous	0.671	Likely Pathogenic	-5.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.31	Pathogenic	0.19	Tolerated			0.2252	0.4050		0	-1	1.9	-31.01
c.1853A>C	Q618P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q618P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are SGM Consensus, ESM1b, FATHMM, PROVEAN, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as uncertain. Overall, the majority of predictions lean toward a benign effect, though a subset of high‑confidence tools suggest pathogenicity. The variant’s status is not contradicted by ClinVar, which has no entry for this change. Based on the collective evidence, Q618P is most likely benign, albeit with some conflicting pathogenic signals from high‑accuracy predictors. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.138725	Uncertain	0.904	0.240	0.000											-8.273	Likely Pathogenic	0.248	Likely Benign	Likely Benign	-0.11	Likely Benign	0.1	3.41	Destabilizing	1.65	Ambiguous	0.23	Likely Benign	0.449	Likely Benign	-3.32	Deleterious	0.261	Benign	0.246	Benign	-1.35	Pathogenic	0.08	Tolerated			0.1990	0.4011		0	-1	1.9	-31.01
c.1892A>C	Q631P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q631P is not reported in ClinVar and has no entry in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining eleven tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the change as pathogenic. The high‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also indicates 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 (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.038963	Uncertain	0.948	0.230	0.000											-16.914	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	4.98	Destabilizing	0.3	11.18	Destabilizing	8.08	Destabilizing	0.56	Ambiguous	0.641	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.75	Benign	0.00	Affected			0.1999	0.2982		0	-1	1.9	-31.01
c.1982A>C	Q661P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from premPS and FATHMM, whereas the remaining 12 tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score) all classify the change as pathogenic or likely pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a pathogenic effect. No prediction is inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-17.549	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	4.11	Destabilizing	0.1	5.97	Destabilizing	5.04	Destabilizing	0.45	Likely Benign	0.531	Likely Pathogenic	-4.58	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.41	Benign	0.01	Affected			0.1811	0.3850		0	-1	1.9	-31.01
c.1985A>C	Q662P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, and FATHMM, while pathogenic predictions are made by SGM‑Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a consistent pathogenic signal: the SGM‑Consensus score (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. AlphaMissense‑Optimized returns an uncertain result, which is treated as unavailable. Overall, the majority of evidence points to a pathogenic impact for Q662P, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-13.174	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	2.15	Destabilizing	0.0	9.37	Destabilizing	5.76	Destabilizing	0.36	Likely Benign	0.268	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.962	Probably Damaging	3.40	Benign	0.08	Tolerated			0.2621	0.4364		0	-1	1.9	-31.01
c.2105A>C	Q702P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; FoldX is uncertain and therefore not counted. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, more tools predict pathogenicity (7) than benignity (5), and the high‑accuracy pathogenic prediction from Foldetta further supports this. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-10.361	Likely Pathogenic	0.324	Likely Benign	Likely Benign	1.76	Ambiguous	0.1	7.05	Destabilizing	4.41	Destabilizing	-0.04	Likely Benign	0.369	Likely Benign	-4.71	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.42	Benign	0.05	Affected			0.1877	0.3371		0	-1	1.9	-31.01
c.2192A>C	Q731P 2D AIThe SynGAP1 missense variant Q731P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.415202	Uncertain	0.507	0.654	0.750											-4.103	Likely Benign	0.066	Likely Benign	Likely Benign										0.125	Likely Benign	-2.08	Neutral	1.000	Probably Damaging	0.987	Probably Damaging	2.64	Benign	0.26	Tolerated			0.2285	0.5385		0	-1	1.9	-31.01
c.2198A>C	Q733P 2D AIThe SynGAP1 missense variant Q733P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875											-4.249	Likely Benign	0.075	Likely Benign	Likely Benign										0.172	Likely Benign	-1.91	Neutral	0.220	Benign	0.308	Benign	2.52	Benign	0.04	Affected			0.2182	0.3894		0	-1	1.9	-31.01
c.2210A>C	Q737P 2D AIThe SynGAP1 missense variant Q737P is listed in ClinVar (ID 2580571.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Taken together, the preponderance of evidence supports a benign classification for Q737P, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.425743	Uncertain	0.323	0.803	0.875					Uncertain		1				-2.407	Likely Benign	0.054	Likely Benign	Likely Benign										0.154	Likely Benign	-1.22	Neutral	0.005	Benign	0.013	Benign	2.78	Benign	0.04	Affected	4.07	3	0.2366	0.4981		-1	0	1.9	-31.01
c.2231A>C	Q744P 2D AIThe SynGAP1 missense variant Q744P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign impact for Q744P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.540428	Binding	0.316	0.866	0.875											-2.062	Likely Benign	0.063	Likely Benign	Likely Benign										0.080	Likely Benign	-0.46	Neutral	0.784	Possibly Damaging	0.206	Benign	2.82	Benign	0.12	Tolerated			0.2584	0.4397		0	-1	1.9	-31.01
c.2267A>C	Q756P 2D AIThe SynGAP1 missense variant Q756P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign 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 Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-4.226	Likely Benign	0.088	Likely Benign	Likely Benign										0.315	Likely Benign	-0.93	Neutral	0.998	Probably Damaging	0.995	Probably Damaging	1.54	Pathogenic	0.23	Tolerated			0.2590	0.5186		0	-1	1.9	-31.01
c.2309A>C	Q770P 2D AIThe SynGAP1 missense variant Q770P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q770P, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-3.948	Likely Benign	0.087	Likely Benign	Likely Benign										0.178	Likely Benign	-1.00	Neutral	0.748	Possibly Damaging	0.170	Benign	4.10	Benign	0.02	Affected			0.2435	0.5717		0	-1	1.9	-31.01
c.2495A>C	Q832P 2D AIThe SynGAP1 missense variant Q832P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.619913	Binding	0.290	0.877	0.375											-1.882	Likely Benign	0.066	Likely Benign	Likely Benign										0.142	Likely Benign	-1.07	Neutral	0.002	Benign	0.005	Benign	2.70	Benign	0.05	Affected			0.1959	0.4368		0	-1	1.9	-31.01
c.2540A>C	Q847P 2D AIThe SynGAP1 missense variant Q847P is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑vs‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (AlphaMissense‑Optimized and AlphaMissense‑Default) indicate a benign outcome, while the consensus of other tools is mixed. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-6.742	Likely Benign	0.320	Likely Benign	Likely Benign										0.331	Likely Benign	-3.83	Deleterious	0.990	Probably Damaging	0.892	Possibly Damaging	2.26	Pathogenic	0.00	Affected			0.2290	0.4831		0	-1	1.9	-31.01
c.2621A>C	Q874P 2D AIThe SynGAP1 missense variant Q874P is reported in gnomAD (ID 6‑33443173‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar classification (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250								6-33443173-A-C	9	5.58e-6	-4.622	Likely Benign	0.125	Likely Benign	Likely Benign										0.219	Likely Benign	-2.89	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.77	Benign	0.00	Affected	3.77	5	0.2373	0.5911		-1	0	1.9	-31.01
c.2678A>C	Q893P 2D AIThe SynGAP1 missense variant Q893P is reported in gnomAD (ID 6‑33443230‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of predictions, including the high‑confidence tools, support a benign classification, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.447267	Uncertain	0.310	0.925	0.750								6-33443230-A-C	1	6.20e-7	-2.463	Likely Benign	0.072	Likely Benign	Likely Benign										0.084	Likely Benign	-0.70	Neutral	0.802	Possibly Damaging	0.432	Benign	2.69	Benign	0.05	Affected	4.32	4	0.2271	0.5151		-1	0	1.9	-31.01
c.2723A>C	Q908P 2D AIThe SynGAP1 missense variant Q908P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for Q908P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250											-4.446	Likely Benign	0.151	Likely Benign	Likely Benign										0.196	Likely Benign	-0.59	Neutral	0.996	Probably Damaging	0.992	Probably Damaging	2.51	Benign	0.11	Tolerated			0.2379	0.5121		0	-1	1.9	-31.01
c.2756A>C	Q919P 2D AIThe SynGAP1 missense variant Q919P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.911223	Binding	0.299	0.841	0.250											-2.358	Likely Benign	0.058	Likely Benign	Likely Benign										0.140	Likely Benign	-1.15	Neutral	0.989	Probably Damaging	0.834	Possibly Damaging	2.38	Pathogenic	0.03	Affected			0.2364	0.6108		0	-1	1.9	-31.01
c.2759A>C	Q920P 2D AIThe SynGAP1 missense variant Q920P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.927260	Binding	0.306	0.845	0.250											-2.127	Likely Benign	0.065	Likely Benign	Likely Benign										0.235	Likely Benign	-1.68	Neutral	0.989	Probably Damaging	0.834	Possibly Damaging	2.58	Benign	0.00	Affected			0.2438	0.5318		0	-1	1.9	-31.01
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.3062A>C	Q1021P 2D AIThe SynGAP1 missense variant Q1021P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1021P, 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 Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500											-3.522	Likely Benign	0.267	Likely Benign	Likely Benign										0.235	Likely Benign	-2.11	Neutral	0.996	Probably Damaging	0.992	Probably Damaging	2.56	Benign	0.02	Affected			0.2022	0.4789		0	-1	1.9	-31.01
c.3074A>C	Q1025P 2D AIThe SynGAP1 missense variant Q1025P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.993410	Binding	0.363	0.746	0.500											-2.151	Likely Benign	0.211	Likely Benign	Likely Benign										0.153	Likely Benign	-1.22	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.72	Benign	0.11	Tolerated			0.2211	0.5196		0	-1	1.9	-31.01
c.3086A>C	Q1029P 2D AIThe SynGAP1 missense variant Q1029P is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available for this variant. Overall, the consensus of all available predictions strongly supports a benign impact, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500											-2.940	Likely Benign	0.124	Likely Benign	Likely Benign										0.105	Likely Benign	-1.23	Neutral	0.005	Benign	0.015	Benign	2.68	Benign	0.15	Tolerated			0.1966	0.4986		0	-1	1.9	-31.01
c.3107A>C	Q1036P 2D AIThe SynGAP1 missense variant Q1036P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a damaging or pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and the consensus score indicates that the variant is most likely benign, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.987955	Binding	0.275	0.765	0.625											-2.491	Likely Benign	0.135	Likely Benign	Likely Benign										0.104	Likely Benign	-2.00	Neutral	0.802	Possibly Damaging	0.238	Benign	2.57	Benign	0.01	Affected			0.2018	0.5564		0	-1	1.9	-31.01
c.3125A>C	Q1042P 2D AIThe SynGAP1 missense variant Q1042P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.959333	Binding	0.310	0.846	0.625											-2.085	Likely Benign	0.060	Likely Benign	Likely Benign										0.461	Likely Benign	-0.73	Neutral	0.586	Possibly Damaging	0.223	Benign	5.42	Benign	0.31	Tolerated			0.2336	0.5762		0	-1	1.9	-31.01
c.3191A>C	Q1064P 2D AIThe SynGAP1 missense variant Q1064P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, 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 Benign		0.978316	Disordered	0.953106	Binding	0.378	0.914	0.875											-2.032	Likely Benign	0.058	Likely Benign	Likely Benign										0.270	Likely Benign	0.93	Neutral	0.001	Benign	0.001	Benign	4.23	Benign	0.20	Tolerated			0.2819	0.4766		0	-1	1.9	-31.01
c.3206A>C	Q1069P 2D AIThe SynGAP1 missense variant Q1069P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.981477	Binding	0.333	0.906	0.875											-3.458	Likely Benign	0.056	Likely Benign	Likely Benign										0.211	Likely Benign	0.75	Neutral	0.977	Probably Damaging	0.722	Possibly Damaging	2.73	Benign	1.00	Tolerated			0.2179	0.5944		0	-1	1.9	-31.01
c.3221A>C	Q1074P 2D AIThe SynGAP1 missense variant Q1074P is listed in gnomAD (ID 6‑33443773‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single outlier. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.987006	Binding	0.339	0.897	0.750								6-33443773-A-C	1	6.23e-7	-4.259	Likely Benign	0.083	Likely Benign	Likely Benign										0.188	Likely Benign	0.52	Neutral	0.925	Possibly Damaging	0.432	Benign	2.66	Benign	0.13	Tolerated	3.77	5	0.2046	0.5784		-1	0	1.9	-31.01
c.3224A>C	Q1075P 2D AIThe SynGAP1 missense variant Q1075P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.988305	Binding	0.354	0.894	0.750											-1.854	Likely Benign	0.086	Likely Benign	Likely Benign										0.175	Likely Benign	0.78	Neutral	0.996	Probably Damaging	0.988	Probably Damaging	2.68	Benign	0.28	Tolerated			0.2288	0.5741		0	-1	1.9	-31.01
c.3245A>C	Q1082P 2D AIThe SynGAP1 missense variant Q1082P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.819762	Disordered	0.979325	Binding	0.347	0.896	0.875											-2.141	Likely Benign	0.064	Likely Benign	Likely Benign										0.287	Likely Benign	-0.71	Neutral	0.001	Benign	0.001	Benign	4.16	Benign	0.05	Affected			0.2121	0.6144		0	-1	1.9	-31.01
c.3278A>C	Q1093P 2D AIThe SynGAP1 missense variant Q1093P is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors classifies it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic effect. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized scores benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely benign, while Foldetta stability analysis is unavailable. Overall, the evidence points to a benign effect for Q1093P, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983312	Binding	0.351	0.886	1.000											-2.613	Likely Benign	0.080	Likely Benign	Likely Benign										0.137	Likely Benign	-0.96	Neutral	0.001	Benign	0.001	Benign	2.69	Benign	0.05	Affected			0.2059	0.5956		0	-1	1.9	-31.01
c.3317A>C	Q1106P 2D AIThe SynGAP1 missense variant Q1106P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence (5 benign vs 4 pathogenic predictions, with a benign high‑accuracy score and no contradictory ClinVar annotation) indicates that the variant is most likely benign. This conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.885302	Disordered	0.952043	Binding	0.382	0.870	0.875											-3.807	Likely Benign	0.077	Likely Benign	Likely Benign										0.162	Likely Benign	-3.14	Deleterious	0.996	Probably Damaging	0.988	Probably Damaging	1.75	Pathogenic	0.31	Tolerated			0.2029	0.5781		0	-1	1.9	-31.01
c.3320A>C	Q1107P 2D AIThe SynGAP1 missense variant Q1107P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign effect for Q1107P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.951017	Binding	0.393	0.880	0.875											-2.643	Likely Benign	0.047	Likely Benign	Likely Benign										0.135	Likely Benign	-2.35	Neutral	0.965	Probably Damaging	0.611	Possibly Damaging	2.57	Benign	0.01	Affected			0.2109	0.5767		0	-1	1.9	-31.01
c.3407A>C	Q1136P 2D AIThe SynGAP1 missense variant Q1136P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1136P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.775584	Binding	0.321	0.884	0.875											-5.067	Likely Benign	0.077	Likely Benign	Likely Benign										0.364	Likely Benign	-1.06	Neutral	0.961	Probably Damaging	0.745	Possibly Damaging	5.42	Benign	0.03	Affected			0.2188	0.5344		0	-1	1.9	-31.01
c.3416A>C	Q1139P 2D AIThe SynGAP1 missense variant Q1139P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, 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 Benign		0.908098	Disordered	0.721191	Binding	0.313	0.866	1.000											-3.753	Likely Benign	0.081	Likely Benign	Likely Benign										0.437	Likely Benign	-1.74	Neutral	0.812	Possibly Damaging	0.396	Benign	5.28	Benign	0.00	Affected			0.2199	0.5349		0	-1	1.9	-31.01
c.344A>C	Q115P 2D AIThe SynGAP1 missense variant Q115P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this assessment does not conflict with the absence of a ClinVar claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750											-2.766	Likely Benign	0.071	Likely Benign	Likely Benign										0.175	Likely Benign	-0.71	Neutral	0.990	Probably Damaging	0.954	Probably Damaging	4.08	Benign	0.46	Tolerated			0.2418	0.4778		0	-1	1.9	-31.01
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.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.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.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.3728A>C	Q1243P 2D AIThe SynGAP1 missense variant Q1243P has no ClinVar record and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. With five tools favoring pathogenicity versus three favoring benign, the overall evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Thus, based on the available predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.545602	Disordered	0.433693	Uncertain	0.887	0.551	0.500											-12.872	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.31	Neutral	0.969	Probably Damaging	0.715	Possibly Damaging	2.65	Benign	0.05	Affected			0.1624	0.3607		0	-1	1.9	-31.01
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.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.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.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.3884A>C	Q1295P 2D AIThe SynGAP1 missense variant Q1295P is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of predictions (5/9) indicate pathogenicity, while 4/9 suggest benignity. Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625											-2.511	Likely Benign	0.168	Likely Benign	Likely Benign										0.372	Likely Benign	-4.95	Deleterious	0.968	Probably Damaging	0.954	Probably Damaging	2.23	Pathogenic	0.00	Affected			0.2299	0.4738		0	-1	1.9	-31.01
c.3893A>C	Q1298P 2D AIThe SynGAP1 missense variant Q1298P 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, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.895297	Binding	0.410	0.821	0.750											-1.819	Likely Benign	0.096	Likely Benign	Likely Benign										0.196	Likely Benign	-2.93	Deleterious	0.586	Possibly Damaging	0.105	Benign	2.76	Benign	0.03	Affected			0.2237	0.4025		0	-1	1.9	-31.01
c.389A>C	Q130P 2D AIThe SynGAP1 missense variant Q130P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign 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 Benign		0.509769	Disordered	0.718853	Binding	0.306	0.885	0.375											-0.659	Likely Benign	0.068	Likely Benign	Likely Benign										0.213	Likely Benign	-0.10	Neutral	0.990	Probably Damaging	0.954	Probably Damaging	4.15	Benign	0.03	Affected			0.2414	0.4466		0	-1	1.9	-31.01
c.3989A>C	Q1330P 2D AIThe SynGAP1 missense variant Q1330P is listed in gnomAD (ID 6‑33451863‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM; pathogenic predictions come from polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an “Uncertain” result, SGM‑Consensus confirms a benign leaning, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the balance of evidence favors a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875								6-33451863-A-C			-3.087	Likely Benign	0.814	Likely Pathogenic	Ambiguous										0.076	Likely Benign	-2.45	Neutral	0.898	Possibly Damaging	0.441	Benign	3.91	Benign	0.03	Affected	3.77	5	0.2266	0.4983		-1	0	1.9	-31.01
c.440A>C	Q147P 2D AIThe SynGAP1 missense variant Q147P is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the balance of evidence, especially the SGM Consensus and the majority of individual 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		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-14.132	Likely Pathogenic	0.797	Likely Pathogenic	Ambiguous										0.264	Likely Benign	-3.03	Deleterious	0.232	Benign	0.147	Benign	3.87	Benign	0.01	Affected			0.2350	0.4402		0	-1	1.9	-31.01
c.473A>C	Q158P 2D AIThe SynGAP1 missense variant Q158P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q158P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.527565	Binding	0.286	0.750	0.375											-6.120	Likely Benign	0.150	Likely Benign	Likely Benign										0.192	Likely Benign	-0.99	Neutral	0.851	Possibly Damaging	0.374	Benign	4.12	Benign	0.03	Affected			0.2167	0.4190		0	-1	1.9	-31.01
c.524A>C	Q175P 2D AIThe SynGAP1 missense variant Q175P is reported in gnomAD (ID 6‑33435166‑A‑C) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the substitution as benign. The consensus from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely benign. High‑accuracy predictors corroborate this assessment: AlphaMissense‑Optimized predicts a benign outcome, and the SGM‑Consensus (majority vote) confirms a likely benign status. No high‑accuracy folding‑stability analysis (Foldetta) is available for this residue, so stability effects remain unassessed. Overall, the collective evidence points to a benign impact for Q175P, and this conclusion is consistent with the absence of a pathogenic ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375								6-33435166-A-C	1	6.20e-7	-6.995	Likely Benign	0.432	Ambiguous	Likely Benign										0.211	Likely Benign	1.55	Neutral	0.396	Benign	0.188	Benign	4.20	Benign	1.00	Tolerated	3.61	5	0.2075	0.4584		-1	0	1.9	-31.01
c.647A>C	Q216P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216P is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, which scores the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; SGM‑Consensus indicates likely pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. premPS is inconclusive and is treated as unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-13.128	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	4.35	Destabilizing	0.8	4.05	Destabilizing	4.20	Destabilizing	0.53	Ambiguous	0.830	Likely Pathogenic	-4.69	Deleterious	0.989	Probably Damaging	0.737	Possibly Damaging	5.84	Benign	0.01	Affected			0.2603	0.5736		0	-1	1.9	-31.01
c.740A>C	Q247P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q247P 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, while the remaining evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact; premPS is uncertain and therefore treated as unavailable. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.490133	Structured	0.283012	Uncertain	0.822	0.339	0.250											-14.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	3.43	Destabilizing	0.2	7.83	Destabilizing	5.63	Destabilizing	0.81	Ambiguous	0.770	Likely Pathogenic	-3.56	Deleterious	0.995	Probably Damaging	0.795	Possibly Damaging	5.69	Benign	0.02	Affected			0.1768	0.3631		0	-1	1.9	-31.01
c.98A>C	Q33P 2D AIThe SynGAP1 missense variant Q33P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.436712	Uncertain	0.342	0.860	0.375											0.546	Likely Benign	0.049	Likely Benign	Likely Benign										0.098	Likely Benign	-0.75	Neutral	0.000	Benign	0.000	Benign	4.21	Benign	0.00	Affected			0.2445	0.5623		0	-1	1.9	-31.01
c.1130T>C	M377T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377T is reported in gnomAD (variant ID 6‑33438035‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence points to a benign effect for M377T, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.675549	Disordered	0.431183	Uncertain	0.324	0.884	0.625								6-33438035-T-C	5	1.17e-5	-1.881	Likely Benign	0.090	Likely Benign	Likely Benign	0.90	Ambiguous	0.4	1.95	Ambiguous	1.43	Ambiguous	0.59	Ambiguous	0.245	Likely Benign	-0.65	Neutral	0.000	Benign	0.002	Benign	5.47	Benign	0.05	Affected	4.32	12	0.3064	0.3267		-1	-1	-2.6	-30.09
c.1226T>C	M409T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) supports a pathogenic outcome; Foldetta remains inconclusive. Overall, the majority of evidence, including the SGM‑Consensus, points to a pathogenic impact for M409T. 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	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000											-9.194	Likely Pathogenic	0.607	Likely Pathogenic	Likely Benign	1.41	Ambiguous	0.2	0.48	Likely Benign	0.95	Ambiguous	0.96	Ambiguous	0.262	Likely Benign	-3.18	Deleterious	0.987	Probably Damaging	0.945	Probably Damaging	4.17	Benign	0.45	Tolerated			0.1835	0.2391		-1	-1	-2.6	-30.09
c.1241T>C	M414T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M414T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta; Rosetta remains uncertain. High‑accuracy methods all support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta predicts a destabilizing, pathogenic outcome. Consequently, the consensus of the most reliable predictors classifies M414T as pathogenic, with no conflict with the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-8.698	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	0.1	1.96	Ambiguous	2.00	Destabilizing	1.27	Destabilizing	0.406	Likely Benign	-5.00	Deleterious	0.997	Probably Damaging	0.972	Probably Damaging	3.41	Benign	0.08	Tolerated			0.1771	0.1976		-1	-1	-2.6	-30.09
c.1289T>C	M430T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430T is reported in gnomAD (6‑33438194‑T‑C) and has no ClinVar entry. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, FoldX (uncertain), Rosetta, Foldetta (uncertain), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as benign or likely benign. No tool predicts pathogenicity. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign, the SGM Consensus is likely benign, and Foldetta is uncertain. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Thus, the variant is most likely benign, and this is not contradictory to ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000								6-33438194-T-C	1	6.19e-7	-3.430	Likely Benign	0.107	Likely Benign	Likely Benign	1.89	Ambiguous	0.1	0.01	Likely Benign	0.95	Ambiguous	0.43	Likely Benign	0.103	Likely Benign	-1.48	Neutral	0.016	Benign	0.010	Benign	3.48	Benign	0.40	Tolerated	3.37	29	0.2002	0.3184		-1	-1	-2.6	-30.09
c.1403T>C	M468T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M468T is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database. Prediction tools that are available all converge on a pathogenic interpretation: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool reports a benign outcome. High‑accuracy assessments are consistent: AlphaMissense‑Optimized is “Uncertain,” SGM Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. **Based on the aggregate predictions, the variant is most likely pathogenic, which does not contradict the ClinVar “Uncertain” classification.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.284882	Structured	0.339253	Uncertain	0.932	0.257	0.000					Uncertain		2	6-33438435-T-C	1	6.20e-7	-12.399	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	3.47	Destabilizing	0.1	3.10	Destabilizing	3.29	Destabilizing	1.84	Destabilizing	0.801	Likely Pathogenic	-3.85	Deleterious	0.994	Probably Damaging	0.985	Probably Damaging	-1.31	Pathogenic	0.01	Affected	3.37	31	0.2094	0.1950		-1	-1	-2.6	-30.09	214.6	47.1	0.0	0.0	0.1	0.0							X	Potentially Pathogenic	The thioether group of Met468, located in the middle of an α helix (res. Ala461–Phe476), interacts with hydrophobic residues (e.g., Phe464, Leu465, Leu489) in an inter-helix space formed by two other α helices (res. Ala461–Phe476, res. Thr488–Gly502). In the variant simulations, the hydrophilic side chain of Thr468 does not pack favorably in the hydrophobic niche, and the methionine-aromatic stacking is lost. Although the hydroxyl group of Thr468 forms an H-bond with the backbone carbonyl group of Phe464, the integrity of the α helix is not affected in the simulations. No large-scale structural changes are observed during the variant simulations; however, due to the importance of hydrophobic packing, the effects could be more pronounced during protein folding.
c.1409T>C	M470T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M470T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy methods further support this: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus 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, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.351497	Uncertain	0.908	0.272	0.000					Uncertain		1				-8.104	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	3.19	Destabilizing	0.1	2.68	Destabilizing	2.94	Destabilizing	1.49	Destabilizing	0.763	Likely Pathogenic	-5.30	Deleterious	0.996	Probably Damaging	0.985	Probably Damaging	-1.08	Pathogenic	0.24	Tolerated	3.37	34	0.1782	0.1950		-1	-1	-2.6	-30.09	213.8	46.5	0.0	0.0	-0.2	0.2		X					X	Potentially Pathogenic	The thioether group of Met470, located in the middle of an α helix (res. Ala461–Phe476), interacts with hydrophobic residues in the inter-helix space (e.g., Val473, Leu558, Cys576, Trp572) formed by two other α helices (res. Ser604–Arg581, res. Pro562–Arg579). In the WT simulations, the Met470 side chain also packs against the positively charged guanidinium groups of Arg575, Arg429, and Arg579, which form salt bridges with the negatively charged carboxylate groups of the Asp474 and Asp467 side chains at the protein surface. In the variant simulations, the hydroxyl group of the Thr470 side chain forms an H-bond with the backbone carbonyl group of Ser466 in the α helix, potentially lowering its structural integrity. Importantly, the hydroxyl group of Thr470 also forms an H-bond with the guanidinium group of Arg575, which helps it form a more permanent salt bridge with Asp467.
c.1430T>C	M477T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477T has no ClinVar entry and is present in gnomAD (ID 6‑33438462‑T‑C). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Default) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic votes); Foldetta remains uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000								6-33438462-T-C	2	1.24e-6	-2.509	Likely Benign	0.373	Ambiguous	Likely Benign	1.62	Ambiguous	0.2	0.16	Likely Benign	0.89	Ambiguous	0.51	Ambiguous	0.273	Likely Benign	-1.33	Neutral	0.765	Possibly Damaging	0.363	Benign	-1.10	Pathogenic	0.40	Tolerated	3.37	34	0.2177	0.1950		-1	-1	-2.6	-30.09
c.1493T>C	M498T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M498T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: all but one (polyPhen‑2 HumVar) predict pathogenicity, while polyPhen‑2 HumVar alone predicts benign. Uncertain predictions (ESM1b and AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy methods reinforce the pathogenic view: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains inconclusive. Overall, the preponderance of evidence indicates that M498T 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	GAP	0.092881	Structured	0.399612	Uncertain	0.932	0.158	0.000											-7.477	In-Between	0.869	Likely Pathogenic	Ambiguous	2.46	Destabilizing	0.1	2.62	Destabilizing	2.54	Destabilizing	1.41	Destabilizing	0.672	Likely Pathogenic	-3.80	Deleterious	0.803	Possibly Damaging	0.343	Benign	-1.19	Pathogenic	0.02	Affected			0.1925	0.1630		-1	-1	-2.6	-30.09
c.1634T>C	M545T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a pathogenic or likely pathogenic outcome. 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’s protein‑folding stability analysis is inconclusive. Taken together, the preponderance of evidence points to a pathogenic effect for M545T. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000											-8.070	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.94	Ambiguous	0.2	0.78	Ambiguous	0.86	Ambiguous	0.97	Ambiguous	0.722	Likely Pathogenic	-5.03	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.24	Pathogenic	0.36	Tolerated			0.1727	0.1847		-1	-1	-2.6	-30.09
c.173T>C	M58T 2D AIThe SynGAP1 missense variant M58T is listed in gnomAD (ID 6‑33423582‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000								6-33423582-T-C	1	6.20e-7	-4.308	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic										0.159	Likely Benign	-1.58	Neutral	0.018	Benign	0.184	Benign	4.09	Benign	0.00	Affected	4.32	1	0.1999	0.2357		-1	-1	-2.6	-30.09
c.1808T>C	M603T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M603T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that provide a clear verdict all classify the substitution as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool in the dataset reports a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus indicates likely pathogenic, while the Foldetta stability analysis is inconclusive and therefore not considered evidence. No contradictory evidence is present in ClinVar. Consequently, the variant is most likely pathogenic based on the available predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-13.152	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	0.2	1.71	Ambiguous	1.71	Ambiguous	0.66	Ambiguous	0.903	Likely Pathogenic	-5.48	Deleterious	0.996	Probably Damaging	0.985	Probably Damaging	-1.29	Pathogenic	0.00	Affected			0.1883	0.1495		-1	-1	-2.6	-30.09
c.1832T>C	M611T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M611T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33440884‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. Four tools (FoldX, Rosetta, Foldetta, premPS) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.236433	Structured	0.210791	Uncertain	0.870	0.253	0.000					Uncertain		1	6-33440884-T-C	1	6.19e-7	-5.696	Likely Benign	0.101	Likely Benign	Likely Benign	1.98	Ambiguous	0.2	0.94	Ambiguous	1.46	Ambiguous	0.87	Ambiguous	0.240	Likely Benign	-2.40	Neutral	0.034	Benign	0.038	Benign	-1.19	Pathogenic	0.29	Tolerated	3.37	35	0.1635	0.1415		-1	-1	-2.6	-30.09
c.1946T>C	M649T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-11.916	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	3.19	Destabilizing	0.2	3.45	Destabilizing	3.32	Destabilizing	1.92	Destabilizing	0.531	Likely Pathogenic	-5.98	Deleterious	0.999	Probably Damaging	0.779	Possibly Damaging	3.35	Benign	0.00	Affected			0.1732	0.1615		-1	-1	-2.6	-30.09
c.1979T>C	M660T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660T is catalogued in gnomAD (ID 6‑33441238‑T‑C) but has no ClinVar entry, so its clinical status is currently unreported. In silico prediction tools largely agree that the substitution is deleterious: pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign effect. High‑accuracy assessments reinforce the pathogenic view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or folding result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000								6-33441238-T-C	1	6.20e-7	-9.791	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	3.62	Destabilizing	0.1	2.05	Destabilizing	2.84	Destabilizing	1.91	Destabilizing	0.561	Likely Pathogenic	-5.99	Deleterious	0.967	Probably Damaging	0.633	Possibly Damaging	3.36	Benign	0.02	Affected	3.38	28	0.1811	0.1630		-1	-1	-2.6	-30.09
c.2264T>C	M755T 2D AIThe SynGAP1 missense variant M755T is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts benign. No tool predicts pathogenicity; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates majority votes from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta data are not available. Overall, the computational evidence overwhelmingly suggests the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.783855	Binding	0.336	0.873	0.375											-4.116	Likely Benign	0.358	Ambiguous	Likely Benign										0.040	Likely Benign	-1.23	Neutral	0.159	Benign	0.053	Benign	2.65	Benign	0.19	Tolerated			0.1944	0.1767		-1	-1	-2.6	-30.09
c.2276T>C	M759T 2D AIThe SynGAP1 missense variant M759T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the SGM consensus and AlphaMissense‑Optimized—supports a benign classification, 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 Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375											-4.202	Likely Benign	0.380	Ambiguous	Likely Benign										0.197	Likely Benign	-1.90	Neutral	0.891	Possibly Damaging	0.315	Benign	2.58	Benign	0.08	Tolerated			0.2063	0.1534		-1	-1	-2.6	-30.09
c.2279T>C	M760T 2D AIThe SynGAP1 missense variant M760T is reported in gnomAD (ID 6‑33441744‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that the variant is most likely benign, 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 Benign		0.541878	Disordered	0.893402	Binding	0.346	0.865	0.375								6-33441744-T-C	1	6.20e-7	-2.365	Likely Benign	0.519	Ambiguous	Likely Benign										0.096	Likely Benign	-1.56	Neutral	0.425	Benign	0.252	Benign	2.71	Benign	0.41	Tolerated	3.99	5	0.2515	0.2875		-1	-1	-2.6	-30.09
c.2318T>C	M773T 2D AIThe SynGAP1 missense variant M773T is listed in gnomAD (ID 6‑33442476‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumVar predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250								6-33442476-T-C	1	1.28e-6	-4.225	Likely Benign	0.377	Ambiguous	Likely Benign										0.112	Likely Benign	-1.63	Neutral	0.106	Benign	0.471	Possibly Damaging	4.22	Benign	0.06	Tolerated	3.64	6	0.2196	0.1586		-1	-1	-2.6	-30.09
c.2342T>C	M781T 2D AIThe SynGAP1 missense variant M781T is catalogued in gnomAD (ID 6‑33442894‑T‑C) and has no ClinVar entry. Across the evaluated in‑silico tools, every predictor classifies the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool reports a pathogenic or likely pathogenic outcome. The high‑accuracy consensus methods reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Based on the unanimous benign predictions and the lack of any ClinVar pathogenic annotation, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.580690	Disordered	0.792850	Binding	0.342	0.889	0.625								6-33442894-T-C	1	6.21e-7	-3.774	Likely Benign	0.310	Likely Benign	Likely Benign										0.175	Likely Benign	-0.86	Neutral	0.015	Benign	0.037	Benign	2.75	Benign	0.59	Tolerated	3.64	6	0.2267	0.1599		-1	-1	-2.6	-30.09
c.2348T>C	M783T 2D AIThe SynGAP1 missense variant M783T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a damaging or pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are not available for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the high‑accuracy consensus points to a benign effect, with no conflict with ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-4.064	Likely Benign	0.299	Likely Benign	Likely Benign										0.111	Likely Benign	-2.08	Neutral	0.625	Possibly Damaging	0.265	Benign	2.69	Benign	0.03	Affected			0.2217	0.2308		-1	-1	-2.6	-30.09
c.2501T>C	M834T 2D AIThe SynGAP1 missense variant M834T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for M834T, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.585406	Disordered	0.640801	Binding	0.258	0.863	0.375											-1.525	Likely Benign	0.332	Likely Benign	Likely Benign										0.137	Likely Benign	-2.03	Neutral	0.224	Benign	0.085	Benign	2.45	Pathogenic	0.00	Affected			0.1757	0.1799		-1	-1	-2.6	-30.09
c.2528T>C	M843T 2D AIThe SynGAP1 missense variant M843T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL and FATHMM, and pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic majority, and Foldetta data are unavailable. Overall, the preponderance of evidence indicates that M843T 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.			0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-7.297	In-Between	0.990	Likely Pathogenic	Likely Pathogenic										0.295	Likely Benign	-3.22	Deleterious	0.968	Probably Damaging	0.954	Probably Damaging	2.62	Benign	0.00	Affected			0.2235	0.2037		-1	-1	-2.6	-30.09
c.2711T>C	M904T 2D AIThe SynGAP1 missense variant M904T is listed in ClinVar (ID 1311496.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.589073	Binding	0.350	0.920	0.250					Uncertain		1				-2.721	Likely Benign	0.668	Likely Pathogenic	Likely Benign										0.042	Likely Benign	-1.15	Neutral	0.277	Benign	0.103	Benign	2.78	Benign	0.18	Tolerated	3.77	5	0.2394	0.2568		-1	-1	-2.6	-30.09
c.2726T>C	M909T 2D AIThe SynGAP1 missense variant M909T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence points to a benign impact for M909T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250											-3.053	Likely Benign	0.647	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-0.74	Neutral	0.901	Possibly Damaging	0.430	Benign	2.86	Benign	1.00	Tolerated			0.2157	0.2085		-1	-1	-2.6	-30.09
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.3092T>C	M1031T 2D AIThe SynGAP1 missense variant M1031T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443644‑T‑C). In silico prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a pathogenic outcome; the only inconclusive result is AlphaMissense‑Default, which is treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus is “Likely Benign,” and Foldetta data are not available. **Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995959	Binding	0.340	0.736	0.500					Uncertain		1	6-33443644-T-C	2	1.24e-6	-1.863	Likely Benign	0.540	Ambiguous	Likely Benign										0.085	Likely Benign	-0.24	Neutral	0.002	Benign	0.005	Benign	2.67	Benign	1.00	Tolerated	3.77	5	0.1587	0.2264		-1	-1	-2.6	-30.09
c.3443T>C	M1148T 2D AIThe SynGAP1 missense variant M1148T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.774279	Binding	0.343	0.835	0.875											-0.972	Likely Benign	0.159	Likely Benign	Likely Benign										0.151	Likely Benign	-1.50	Neutral	0.001	Benign	0.002	Benign	2.56	Benign	0.00	Affected			0.2063	0.2214		-1	-1	-2.6	-30.09
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.353T>C	M118T 2D AIThe SynGAP1 missense variant M118T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM‑Consensus) also indicates a likely benign classification, and AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the evidence from multiple independent predictors and the high‑accuracy consensus strongly supports a benign impact. This conclusion is consistent with the lack of any ClinVar pathogenic 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 Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-2.468	Likely Benign	0.454	Ambiguous	Likely Benign										0.217	Likely Benign	-2.41	Neutral	0.396	Benign	0.067	Benign	3.86	Benign	0.08	Tolerated			0.2207	0.2237		-1	-1	-2.6	-30.09
c.3560T>C	M1187T 2D AIThe SynGAP1 missense variant M1187T is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as benign, and Foldetta results are unavailable. Overall, the majority of individual predictors (seven) indicate pathogenicity, whereas only three suggest benignity. Consequently, the variant is most likely pathogenic based on the available computational evidence, 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 Benign	Coiled-coil	0.562014	Disordered	0.499801	Uncertain	0.597	0.636	0.625											-3.502	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.597	Likely Pathogenic	-1.75	Neutral	0.968	Probably Damaging	0.954	Probably Damaging	5.63	Benign	0.04	Affected			0.2378	0.1757		-1	-1	-2.6	-30.09
c.3632T>C	M1211T 2D AIThe SynGAP1 missense variant M1211T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those predicting pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact, 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 Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500											-3.885	Likely Benign	0.669	Likely Pathogenic	Likely Benign										0.448	Likely Benign	-1.99	Neutral	0.987	Probably Damaging	0.968	Probably Damaging	5.54	Benign	0.02	Affected			0.1987	0.1614		-1	-1	-2.6	-30.09
c.3704T>C	M1235T 2D AIThe SynGAP1 missense variant M1235T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign impact. This prediction does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125											-5.381	Likely Benign	0.149	Likely Benign	Likely Benign										0.060	Likely Benign	-2.39	Neutral	0.425	Benign	0.158	Benign	2.66	Benign	0.01	Affected			0.2079	0.1814		-1	-1	-2.6	-30.09
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.3839T>C	M1280T 2D AIThe SynGAP1 missense variant M1280T is catalogued in gnomAD (6‑33447887‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. In contrast, SIFT and FATHMM predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875								6-33447887-T-C	3	1.93e-6	-2.305	Likely Benign	0.112	Likely Benign	Likely Benign										0.158	Likely Benign	-2.26	Neutral	0.369	Benign	0.120	Benign	2.34	Pathogenic	0.00	Affected	3.77	5	0.1814	0.2031		-1	-1	-2.6	-30.09
c.47T>C	M16T 2D AIThe SynGAP1 missense variant M16T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign and the SGM‑Consensus classifies it as likely benign. No Foldetta stability analysis is available for this residue, so folding‑stability evidence is lacking. Overall, the majority of computational evidence indicates that M16T is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375											-2.060	Likely Benign	0.515	Ambiguous	Likely Benign										0.065	Likely Benign	-0.46	Neutral	0.006	Benign	0.001	Benign	4.23	Benign	0.00	Affected			0.2385	0.2545		-1	-1	-2.6	-30.09
c.521T>C	M174T 2D AIThe SynGAP1 missense variant M174T 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 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 (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, 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		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-9.174	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.286	Likely Benign	-3.12	Deleterious	0.244	Benign	0.049	Benign	4.08	Benign	0.01	Affected			0.1949	0.2334		-1	-1	-2.6	-30.09
c.866T>C	M289T 2D AIThe SynGAP1 missense variant M289T is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a benign effect. Taken together, the majority of evidence indicates that M289T is most likely benign, and this conclusion does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000					Uncertain		1				-4.668	Likely Benign	0.238	Likely Benign	Likely Benign	0.73	Ambiguous	0.1	0.17	Likely Benign	0.45	Likely Benign	-0.01	Likely Benign	0.222	Likely Benign	-0.47	Neutral	0.801	Possibly Damaging	0.315	Benign	1.83	Pathogenic	0.57	Tolerated			0.1657	0.1534		-1	-1	-2.6	-30.09
c.86T>C	M29T 2D AIThe SynGAP1 missense variant M29T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that M29T is most likely benign, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250					Uncertain		1				-2.167	Likely Benign	0.122	Likely Benign	Likely Benign										0.199	Likely Benign	-0.37	Neutral	0.018	Benign	0.184	Benign	4.33	Benign	0.00	Affected	4.32	1	0.2633	0.2716		-1	-1	-2.6	-30.09
c.1039A>G	T347A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T347A is catalogued in gnomAD (ID 6‑33437944‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated. Only FATHMM predicts a pathogenic outcome, while Foldetta, premPS, and Rosetta are inconclusive. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta remains uncertain. Overall, the consensus of the majority of tools indicates the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.268042	Structured	0.349915	Uncertain	0.951	0.434	0.000								6-33437944-A-G	9	5.58e-6	-5.858	Likely Benign	0.086	Likely Benign	Likely Benign	0.34	Likely Benign	0.1	0.70	Ambiguous	0.52	Ambiguous	0.70	Ambiguous	0.093	Likely Benign	-1.52	Neutral	0.031	Benign	0.016	Benign	1.68	Pathogenic	0.42	Tolerated	3.37	25	0.4032	0.4615		0	1	2.5	-30.03
c.1054A>G	T352A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts pathogenic, while Rosetta remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign verdict; and Foldetta, integrating FoldX‑MD (benign) and Rosetta (uncertain), reports benign stability. Overall, the preponderance of evidence indicates that T352A is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000											-1.952	Likely Benign	0.055	Likely Benign	Likely Benign	0.12	Likely Benign	0.0	0.50	Ambiguous	0.31	Likely Benign	0.45	Likely Benign	0.032	Likely Benign	-1.09	Neutral	0.031	Benign	0.024	Benign	1.73	Pathogenic	0.29	Tolerated			0.4341	0.4938		1	0	2.5	-30.03
c.1075A>G	T359A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T359A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250											-2.948	Likely Benign	0.062	Likely Benign	Likely Benign	0.09	Likely Benign	0.0	0.73	Ambiguous	0.41	Likely Benign	0.45	Likely Benign	0.103	Likely Benign	-0.73	Neutral	0.000	Benign	0.001	Benign	1.79	Pathogenic	0.34	Tolerated			0.4215	0.4713		1	0	2.5	-30.03
c.1084T>A	W362R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as pathogenic. Benign predictions are absent; all evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return pathogenic or likely pathogenic calls. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports pathogenic. Consequently, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-14.004	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.64	Destabilizing	0.3	3.90	Destabilizing	3.27	Destabilizing	1.10	Destabilizing	0.706	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.28	Pathogenic	0.00	Affected	3.39	24	0.4811	0.0571		2	-3	-3.6	-30.03	287.5	-34.1	-0.2	0.1	-0.6	0.2	X			X			X	Potentially Pathogenic	The indole ring of Trp362, located on the surface of an anti-parallel β sheet (res. Thr359-Pro364) in the C2 domain, stacks with nearby residues (e.g., Arg401, Arg272). In the variant simulations, the guanidinium group of the introduced residue Arg362 forms a salt bridge with the carboxylate group of Glu273 and, like Trp362, stacks with other arginine residues (e.g., Arg401, Arg272). This residue is at both the C2-membrane interface and the C2-RasGTPase interface, so the residue swap could potentially affect both interactions. However, these phenomena cannot be addressed using solvent-only simulations. Notably, Arg272, which stacks with both the non-mutated Trp362 and the mutated Arg362, forms a salt bridge directly with Asp105 of Ras in the WT simulations. Therefore, the residue swap could affect the C2 domain stability, the SynGAP-membrane association, and the SynGAP-Ras association.	10.1016/j.ajhg.2020.11.011
c.1084T>C	W362R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362R (ClinVar ID 41461.0) is listed as Pathogenic and is not reported in gnomAD. All available in silico predictors classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125					Pathogenic		2				-14.004	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	2.64	Destabilizing	0.3	3.90	Destabilizing	3.27	Destabilizing	1.10	Destabilizing	0.706	Likely Pathogenic	-12.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.28	Pathogenic	0.00	Affected	3.39	24	0.4811	0.0571		2	-3	-3.6	-30.03	287.5	-34.1	-0.2	0.1	-0.6	0.2	X			X			X	Potentially Pathogenic	The indole ring of Trp362, located on the surface of an anti-parallel β sheet (res. Thr359-Pro364) in the C2 domain, stacks with nearby residues (e.g., Arg401, Arg272). In the variant simulations, the guanidinium group of the introduced residue Arg362 forms a salt bridge with the carboxylate group of Glu273 and, like Trp362, stacks with other arginine residues (e.g., Arg401, Arg272). This residue is at both the C2-membrane interface and the C2-RasGTPase interface, so the residue swap could potentially affect both interactions. However, these phenomena cannot be addressed using solvent-only simulations. Notably, Arg272, which stacks with both the non-mutated Trp362 and the mutated Arg362, forms a salt bridge directly with Asp105 of Ras in the WT simulations. Therefore, the residue swap could affect the C2 domain stability, the SynGAP-membrane association, and the SynGAP-Ras association.	10.1016/j.ajhg.2020.11.011
c.1096A>G	T366A 2D AIThe SynGAP1 missense variant T366A is not reported in ClinVar and is absent from gnomAD. Consensus among most in silico predictors indicates a benign effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated. Only FATHMM predicts a pathogenic outcome, while Foldetta, premPS, and Rosetta are inconclusive and are treated as unavailable evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, and Foldetta provides no definitive stability change. Overall, the computational evidence overwhelmingly favors a benign classification, and this is consistent with the absence of any ClinVar assertion. Therefore, the variant is most likely benign, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.441902	Uncertain	0.897	0.642	0.250											-3.983	Likely Benign	0.082	Likely Benign	Likely Benign	0.21	Likely Benign	0.5	0.86	Ambiguous	0.54	Ambiguous	0.51	Ambiguous	0.046	Likely Benign	-0.94	Neutral	0.031	Benign	0.016	Benign	1.73	Pathogenic	0.45	Tolerated			0.4141	0.4785		1	0	2.5	-30.03
c.1105A>G	T369A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T369A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while Rosetta and Foldetta are inconclusive. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that T369A is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.468512	Structured	0.437011	Uncertain	0.417	0.707	0.500											-1.957	Likely Benign	0.056	Likely Benign	Likely Benign	0.09	Likely Benign	0.1	1.18	Ambiguous	0.64	Ambiguous	0.26	Likely Benign	0.090	Likely Benign	-1.93	Neutral	0.012	Benign	0.016	Benign	1.72	Pathogenic	0.30	Tolerated			0.4538	0.5053		1	0	2.5	-30.03
c.1111A>G	S371G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S371G is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined—REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—classifies the substitution as benign. No pathogenic predictions are present. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375											-2.073	Likely Benign	0.053	Likely Benign	Likely Benign	0.47	Likely Benign	0.3	0.49	Likely Benign	0.48	Likely Benign	0.35	Likely Benign	0.164	Likely Benign	-1.32	Neutral	0.213	Benign	0.067	Benign	4.63	Benign	0.17	Tolerated			0.3192	0.5295		1	0	0.4	-30.03
c.1222A>G	T408A 2D AISynGAP1 missense variant T408A is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv), and ESM1b. The high‑accuracy AlphaMissense‑Optimized score is benign, while the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, a protein‑folding stability method, also predicts benign. Overall, the balance of evidence favors a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000					Uncertain		1				-8.304	Likely Pathogenic	0.114	Likely Benign	Likely Benign	0.37	Likely Benign	0.6	-0.06	Likely Benign	0.16	Likely Benign	0.72	Ambiguous	0.118	Likely Benign	-3.07	Deleterious	0.540	Possibly Damaging	0.131	Benign	4.16	Benign	0.14	Tolerated			0.3970	0.4674		1	0	2.5	-30.03
c.1228A>G	S410G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S410G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000											-7.147	In-Between	0.137	Likely Benign	Likely Benign	0.58	Ambiguous	0.1	1.33	Ambiguous	0.96	Ambiguous	0.85	Ambiguous	0.117	Likely Benign	-2.54	Deleterious	0.952	Possibly Damaging	0.145	Benign	4.13	Benign	0.19	Tolerated			0.2651	0.5143		1	0	0.4	-30.03
c.1273A>G	T425A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Two tools (premPS and AlphaMissense‑Optimized) give uncertain results and are treated as unavailable. High‑accuracy assessments show SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign, and AlphaMissense‑Optimized as uncertain. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-8.945	Likely Pathogenic	0.799	Likely Pathogenic	Ambiguous	-0.31	Likely Benign	0.1	-0.05	Likely Benign	-0.18	Likely Benign	0.70	Ambiguous	0.372	Likely Benign	-4.17	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.42	Benign	0.09	Tolerated			0.2971	0.2572		1	0	2.5	-30.03
c.130T>A	W44R 2D AIThe SynGAP1 W44R missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of tools (seven pathogenic vs. three benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, and this prediction 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.			0.301917	Structured	0.431379	Uncertain	0.377	0.748	0.375											-4.850	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.291	Likely Benign	-5.06	Deleterious	0.943	Possibly Damaging	0.888	Possibly Damaging	3.16	Benign	0.00	Affected			0.4268	0.0749		2	-3	-3.6	-30.03
c.130T>C	W44R 2D AISynGAP1 W44R is not reported in ClinVar and is absent from gnomAD. Consensus from standard predictors shows a split: benign calls come from REVEL, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessment focuses on AlphaMissense‑Optimized, which predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, 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.			0.301917	Structured	0.431379	Uncertain	0.377	0.748	0.375											-4.850	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.291	Likely Benign	-5.06	Deleterious	0.943	Possibly Damaging	0.888	Possibly Damaging	3.16	Benign	0.00	Affected			0.4268	0.0749		2	-3	-3.6	-30.03
c.1345A>G	S449G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449G is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (variant ID 6‑33438250‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as “Likely Benign,” and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000					Uncertain		1	6-33438250-A-G	3	1.86e-6	-5.936	Likely Benign	0.071	Likely Benign	Likely Benign	0.47	Likely Benign	0.0	0.55	Ambiguous	0.51	Ambiguous	0.85	Ambiguous	0.116	Likely Benign	-2.32	Neutral	0.948	Possibly Damaging	0.124	Benign	3.35	Benign	0.13	Tolerated	3.37	32	0.2600	0.3718		0	1	0.4	-30.03
c.1369A>G	S457G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S457G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for S457G. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-9.154	Likely Pathogenic	0.811	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.0	0.87	Ambiguous	0.87	Ambiguous	0.65	Ambiguous	0.382	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	3.35	Benign	0.13	Tolerated			0.2735	0.4074		1	0	0.4	-30.03
c.1372A>G	T458A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T458A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of reliable predictors (six pathogenic vs. five benign) indicate a pathogenic effect. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-10.734	Likely Pathogenic	0.924	Likely Pathogenic	Ambiguous	0.36	Likely Benign	0.0	0.31	Likely Benign	0.34	Likely Benign	0.56	Ambiguous	0.358	Likely Benign	-4.27	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.40	Benign	0.15	Tolerated			0.4137	0.4257		1	0	2.5	-30.03
c.1462A>G	T488A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T488A is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the majority of tools (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) predict pathogenicity; Rosetta and premPS are uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence indicates that T488A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-11.341	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.2	1.99	Ambiguous	2.06	Destabilizing	0.57	Ambiguous	0.497	Likely Benign	-4.64	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.24	Benign	0.01	Affected			0.2871	0.2872		1	0	2.5	-30.03
c.1471A>G	T491A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T491A is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (gnomAD ID: 6‑33438503‑A‑G). Prediction tools that agree on a benign effect include FoldX, Rosetta, and Foldetta. Tools that predict a pathogenic effect include SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (10 pathogenic vs. 3 benign) indicate a likely pathogenic impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125								6-33438503-A-G	1	6.20e-7	-11.033	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.10	Likely Benign	0.3	-0.27	Likely Benign	-0.09	Likely Benign	1.06	Destabilizing	0.851	Likely Pathogenic	-4.82	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.47	Pathogenic	0.01	Affected	3.37	35	0.3903	0.2874		0	1	2.5	-30.03
c.1594A>G	T532A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T532A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only FATHMM predicts a pathogenic outcome. Grouping by consensus, the benign‑predicting tools outnumber the single pathogenic prediction. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. No prediction or stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.275179	Structured	0.021478	Uncertain	0.889	0.385	0.000											-2.907	Likely Benign	0.088	Likely Benign	Likely Benign	0.16	Likely Benign	0.0	0.13	Likely Benign	0.15	Likely Benign	0.11	Likely Benign	0.165	Likely Benign	-0.80	Neutral	0.032	Benign	0.023	Benign	-1.15	Pathogenic	0.14	Tolerated			0.3573	0.3114		1	0	2.5	-30.03
c.1603A>G	S535G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S535G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. Uncertain or inconclusive results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for S535G, and this conclusion does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.236433	Structured	0.041365	Uncertain	0.918	0.343	0.000											-4.619	Likely Benign	0.143	Likely Benign	Likely Benign	0.19	Likely Benign	0.0	0.93	Ambiguous	0.56	Ambiguous	0.64	Ambiguous	0.247	Likely Benign	-1.75	Neutral	0.606	Possibly Damaging	0.114	Benign	-1.30	Pathogenic	0.19	Tolerated			0.2858	0.4644		1	0	0.4	-30.03
c.1714T>A	W572R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W572R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while no tool predicts a benign outcome. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this 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	0.150080	Structured	0.039626	Uncertain	0.935	0.256	0.000											-17.511	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	4.84	Destabilizing	0.1	6.19	Destabilizing	5.52	Destabilizing	1.79	Destabilizing	0.894	Likely Pathogenic	-12.81	Deleterious					-1.25	Pathogenic	0.00	Affected	3.37	35	0.4059	0.0212		2	-3	-3.6	-30.03	312.6	-37.6	0.0	0.0	-1.0	0.0		X	X					Potentially Pathogenic	The indole ring of Trp572, located in an α-helix (res. Arg563-Glu578), lies in a hydrophobic inter-helix space, where it makes extensive hydrophobic interactions with nearby residues such as Met470, Phe569, Leu588, and Ile589. The guanidinium group of Arg572 is similarly sized to the tryptophan it replaced; however, it is also positively charged. In the variant simulations, Arg572 forms hydrogen bonds with other residues in the inter-helix space, such as Ser592 and the backbone carbonyl atom of Leu465. Additionally, Arg572 hydrophobically packs its carbon chain with surrounding residues such as Phe569 and Ile589.However, the introduced residue arginine is too hydrophilic and charged for the hydrophobic space, disrupting the hydrophobic packing of the inter-helix space. Indeed, in the second simulation, Arg572 successfully escapes the hydrophobic niche completely, causing the whole protein to partially unfold.Overall, the residue swap is highly likely to cause critical protein folding problems, as evidenced by the effects seen in the variant simulations.
c.1714T>C	W572R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W572R is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous computational evidence, 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	GAP	0.150080	Structured	0.039626	Uncertain	0.935	0.256	0.000					Not provided		1				-17.511	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	4.84	Destabilizing	0.1	6.19	Destabilizing	5.52	Destabilizing	1.79	Destabilizing	0.894	Likely Pathogenic	-12.81	Deleterious					-1.25	Pathogenic	0.00	Affected	3.37	35	0.4059	0.0212		2	-3	-3.6	-30.03	312.6	-37.6	0.0	0.0	-1.0	0.0		X	X					Potentially Pathogenic	The indole ring of Trp572, located in an α-helix (res. Arg563-Glu578), lies in a hydrophobic inter-helix space, where it makes extensive hydrophobic interactions with nearby residues such as Met470, Phe569, Leu588, and Ile589. The guanidinium group of Arg572 is similarly sized to the tryptophan it replaced; however, it is also positively charged. In the variant simulations, Arg572 forms hydrogen bonds with other residues in the inter-helix space, such as Ser592 and the backbone carbonyl atom of Leu465. Additionally, Arg572 hydrophobically packs its carbon chain with surrounding residues such as Phe569 and Ile589.However, the introduced residue arginine is too hydrophilic and charged for the hydrophobic space, disrupting the hydrophobic packing of the inter-helix space. Indeed, in the second simulation, Arg572 successfully escapes the hydrophobic niche completely, causing the whole protein to partially unfold.Overall, the residue swap is highly likely to cause critical protein folding problems, as evidenced by the effects seen in the variant simulations.
c.1768A>G	S590G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S590G is listed in ClinVar (ID 1721675.0) with an uncertain significance status and is present in gnomAD (6‑33440820‑A‑G). Functional prediction tools that report a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic majority. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive, as are FoldX, Rosetta, and premPS. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022667	Structured	0.088943	Uncertain	0.918	0.199	0.000					Conflicting		2	6-33440820-A-G	14	8.67e-6	-14.277	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.1	1.28	Ambiguous	0.98	Ambiguous	0.71	Ambiguous	0.379	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.922	Probably Damaging	3.42	Benign	0.06	Tolerated	3.37	35	0.2627	0.4118		1	0	0.4	-30.03	186.7	49.4	0.0	0.0	0.1	0.0		X						Potentially Pathogenic	In the WT simulations, the hydroxyl group of Ser590, located on an α helix (res. Glu582-Met603), forms hydrogen bonds with the backbone carbonyl of Ala634 and/or the carboxamide group of the Asn635 side chain at the end of the opposing α helix (res. Thr619-Ala634).The residue swap could weaken the integrity of the α helix, as glycine is known as an “α helix breaker.” However, no discernible difference was observed between the WT and variant simulations in this regard. Importantly, Gly590 cannot form hydrogen bonds with the opposing helix in the same way that serine can, which could weaken the tertiary structure assembly between the two helices.
c.1816A>G	S606G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S606G is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is treated as unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.281	Likely Pathogenic	0.603	Likely Pathogenic	Likely Benign	0.43	Likely Benign	0.1	1.42	Ambiguous	0.93	Ambiguous	0.84	Ambiguous	0.229	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	3.35	Benign	0.04	Affected			0.2286	0.3279		1	0	0.4	-30.03
c.1855A>G	T619A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T619A missense variant is not reported in ClinVar and has no gnomAD entry. Consensus prediction tools cluster into two groups: benign predictions come from SIFT, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the change as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as likely pathogenic; Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points toward a pathogenic effect, 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	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000											-6.341	Likely Benign	0.672	Likely Pathogenic	Likely Benign	0.59	Ambiguous	0.1	0.62	Ambiguous	0.61	Ambiguous	0.53	Ambiguous	0.613	Likely Pathogenic	-4.21	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	-1.27	Pathogenic	0.17	Tolerated			0.3915	0.3109		1	0	2.5	-30.03
c.1864A>G	T622A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622A is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FoldX, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools with uncertain or inconclusive results—AlphaMissense‑Optimized, Rosetta, Foldetta, and premPS—are treated as unavailable for pathogenicity assessment. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for T622A, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-10.953	Likely Pathogenic	0.827	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	1.04	Ambiguous	0.54	Ambiguous	0.75	Ambiguous	0.893	Likely Pathogenic	-4.58	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.52	Pathogenic	0.01	Affected			0.3191	0.3091		1	0	2.5	-30.03
c.1870A>G	T624A 2D AIThe SynGAP1 T624A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are FoldX and Foldetta, while the majority of tools—REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic outcome. Uncertain predictions come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the preponderance of evidence points to a pathogenic effect for T624A, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-12.967	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	-0.38	Likely Benign	0.4	0.51	Ambiguous	0.07	Likely Benign	0.80	Ambiguous	0.895	Likely Pathogenic	-4.94	Deleterious	0.962	Probably Damaging	0.694	Possibly Damaging	-1.45	Pathogenic	0.03	Affected			0.2903	0.2872		1	0	2.5	-30.03
c.1918A>G	T640A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN, REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), and SIFT all score the substitution as benign. No tool predicts pathogenicity; only Rosetta yields an uncertain result. High‑accuracy assessments corroborate this benign trend: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Taken together, the evidence overwhelmingly supports a benign classification for T640A, and this conclusion does not contradict any ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-3.068	Likely Benign	0.074	Likely Benign	Likely Benign	0.14	Likely Benign	0.1	0.93	Ambiguous	0.54	Ambiguous	-0.17	Likely Benign	0.078	Likely Benign	0.51	Neutral	0.009	Benign	0.001	Benign	3.51	Benign	0.42	Tolerated			0.3834	0.3202		1	0	2.5	-30.03
c.1969T>A	W657R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score, which is labeled Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and the Foldetta stability analysis is inconclusive. Overall, the majority of evidence points to a pathogenic impact for W657R, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-13.391	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.2	1.64	Ambiguous	1.60	Ambiguous	1.29	Destabilizing	0.461	Likely Benign	-11.96	Deleterious	0.999	Probably Damaging	0.964	Probably Damaging	3.48	Benign	0.07	Tolerated			0.4684	0.0000		2	-3	-3.6	-30.03
c.1969T>C	W657R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority of the four high‑accuracy tools) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. FoldX and Rosetta individually report uncertain effects on protein stability. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-13.391	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.2	1.64	Ambiguous	1.60	Ambiguous	1.29	Destabilizing	0.461	Likely Benign	-11.96	Deleterious	0.999	Probably Damaging	0.964	Probably Damaging	3.48	Benign	0.07	Tolerated			0.4684	0.0000		2	-3	-3.6	-30.03
c.2014A>G	T672A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T672A is listed in ClinVar as Benign (ClinVar ID 2154412.0) and is present in gnomAD (variant ID 6‑33441273‑A‑G). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only PROVEAN predicts a pathogenic outcome. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a benign effect, and this conclusion is consistent with the ClinVar designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000					Benign		1	6-33441273-A-G	3	1.86e-6	-6.524	Likely Benign	0.109	Likely Benign	Likely Benign	0.51	Ambiguous	0.3	1.15	Ambiguous	0.83	Ambiguous	0.65	Ambiguous	0.046	Likely Benign	-3.20	Deleterious	0.006	Benign	0.002	Benign	3.44	Benign	0.12	Tolerated	3.40	25	0.3687	0.4380		1	0	2.5	-30.03	188.5	42.5	-0.1	0.3	0.2	0.0		X						Potentially Pathogenic	The hydroxyl group of Thr672, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop itself, such as Lys566, Glu666, and Asn669. In the variant simulations, Ala672 can only form a hydrogen bond with Lys566 via its backbone carbonyl group. Consequently, it cannot maintain the Lys566-Glu666 salt bridge through hydrogen bonding, leading to a significant disruption of the intricate and stable hydrogen-bond network between the loop and the helices.
c.2020A>G	T674A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly favor a benign effect: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, REVEL, FoldX, premPS, Foldetta, and the SGM‑Consensus score all indicate benign or likely benign. No tool predicts pathogenicity; the only inconclusive result comes from Rosetta, which is listed as uncertain. High‑accuracy methods corroborate the benign assessment: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000											-5.915	Likely Benign	0.099	Likely Benign	Likely Benign	-0.13	Likely Benign	0.0	0.89	Ambiguous	0.38	Likely Benign	0.29	Likely Benign	0.052	Likely Benign	-1.48	Neutral	0.398	Benign	0.045	Benign	3.45	Benign	0.28	Tolerated			0.4042	0.4845		1	0	2.5	-30.03
c.2026A>G	S676G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. Two tools (ESM1b and premPS) returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta predicts a benign stability change. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-7.249	In-Between	0.117	Likely Benign	Likely Benign	0.38	Likely Benign	0.1	0.25	Likely Benign	0.32	Likely Benign	0.67	Ambiguous	0.132	Likely Benign	-2.74	Deleterious	0.855	Possibly Damaging	0.100	Benign	3.39	Benign	0.02	Affected			0.2772	0.4342		1	0	0.4	-30.03
c.2029A>G	S677G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. Predictions that are inconclusive—FoldX, Rosetta, Foldetta, and premPS—are treated as unavailable. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the evidence supports a benign classification for S677G, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-5.126	Likely Benign	0.060	Likely Benign	Likely Benign	0.98	Ambiguous	0.1	1.20	Ambiguous	1.09	Ambiguous	0.64	Ambiguous	0.126	Likely Benign	-1.38	Neutral	0.002	Benign	0.001	Benign	3.30	Benign	0.26	Tolerated			0.2885	0.5325		1	0	0.4	-30.03
c.2032A>G	S678G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, REVEL, FoldX, premPS, and Foldetta. No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is listed as “Uncertain.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-4.379	Likely Benign	0.069	Likely Benign	Likely Benign	0.24	Likely Benign	0.2	0.55	Ambiguous	0.40	Likely Benign	-0.24	Likely Benign	0.082	Likely Benign	1.90	Neutral	0.000	Benign	0.001	Benign	3.43	Benign	1.00	Tolerated			0.2807	0.4961		1	0	0.4	-30.03
c.2071A>G	T691A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or tolerated. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while premPS and ESM1b are uncertain. The SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction contradicts the ClinVar status, which is currently unreported. Based on the preponderance of evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-7.840	In-Between	0.086	Likely Benign	Likely Benign	-0.11	Likely Benign	0.0	0.22	Likely Benign	0.06	Likely Benign	0.69	Ambiguous	0.063	Likely Benign	-1.84	Neutral	0.751	Possibly Damaging	0.131	Benign	3.49	Benign	0.33	Tolerated			0.2819	0.3251		1	0	2.5	-30.03
c.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.2110A>G	S704G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Taken together, the majority of reliable predictors indicate a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-7.827	In-Between	0.169	Likely Benign	Likely Benign	1.05	Ambiguous	0.1	1.33	Ambiguous	1.19	Ambiguous	0.53	Ambiguous	0.091	Likely Benign	-2.25	Neutral	0.981	Probably Damaging	0.514	Possibly Damaging	3.42	Benign	0.07	Tolerated			0.2224	0.3378		1	0	0.4	-30.03
c.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.2167A>G	T723A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess sequence conservation, structural impact, or functional effect all converge on a benign outcome: SIFT, PolyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, REVEL, and the protein‑stability predictors FoldX, Rosetta, premPS, and Foldetta all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Based on the uniform predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375											-4.572	Likely Benign	0.064	Likely Benign	Likely Benign	-0.47	Likely Benign	0.0	0.16	Likely Benign	-0.16	Likely Benign	0.25	Likely Benign	0.053	Likely Benign	-0.91	Neutral	0.161	Benign	0.045	Benign	3.51	Benign	0.06	Tolerated			0.3902	0.3639		1	0	2.5	-30.03
c.2203A>G	S735G 2D AIThe SynGAP1 missense variant S735G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the majority of evidence, the variant is most likely benign, 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 Benign		0.916840	Disordered	0.412174	Uncertain	0.290	0.752	0.875											-5.986	Likely Benign	0.083	Likely Benign	Likely Benign										0.097	Likely Benign	-0.55	Neutral	0.953	Possibly Damaging	0.744	Possibly Damaging	2.68	Benign	0.23	Tolerated			0.2777	0.4089		1	0	0.4	-30.03
c.220A>G	S74G 2D AIThe SynGAP1 missense variant S74G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion 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 Benign		0.505461	Disordered	0.450156	Uncertain	0.294	0.831	0.500											-3.540	Likely Benign	0.071	Likely Benign	Likely Benign										0.028	Likely Benign	-1.30	Neutral	0.000	Benign	0.000	Benign	4.08	Benign	0.00	Affected			0.2347	0.3749		1	0	0.4	-30.03
c.2212A>G	S738G 2D AIThe SynGAP1 missense variant S738G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign 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 Benign		0.812494	Disordered	0.441162	Uncertain	0.284	0.827	0.875											-3.863	Likely Benign	0.053	Likely Benign	Likely Benign										0.055	Likely Benign	-1.53	Neutral	0.002	Benign	0.003	Benign	2.66	Benign	0.01	Affected			0.2032	0.3385		1	0	0.4	-30.03
c.2293A>G	S765G 2D AIThe SynGAP1 missense variant S765G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.370445	Structured	0.922652	Binding	0.335	0.865	0.250											-4.658	Likely Benign	0.152	Likely Benign	Likely Benign										0.048	Likely Benign	-0.98	Neutral	0.963	Probably Damaging	0.950	Probably Damaging	4.09	Benign	0.05	Affected			0.2894	0.4946		1	0	0.4	-30.03
c.229A>G	S77G 2D AIThe SynGAP1 missense variant S77G is reported in gnomAD (variant ID 6‑33425837‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact for S77G. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375								6-33425837-A-G	2	1.24e-6	-3.571	Likely Benign	0.064	Likely Benign	Likely Benign										0.014	Likely Benign	-1.23	Neutral	0.022	Benign	0.003	Benign	4.09	Benign	0.00	Affected	4.32	1	0.2204	0.3866		0	1	0.4	-30.03
c.2335A>G	S779G 2D AIThe SynGAP1 missense variant S779G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.304	Likely Benign	0.111	Likely Benign	Likely Benign										0.103	Likely Benign	0.38	Neutral	0.393	Benign	0.324	Benign	2.65	Benign	0.53	Tolerated			0.2894	0.5087		1	0	0.4	-30.03
c.2368A>G	T790A 2D AIThe SynGAP1 T790A 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, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, while the SGM Consensus remains inconclusive and Foldetta data are unavailable. Overall, the majority of standard predictors indicate pathogenicity, but the single high‑accuracy tool that is available suggests a benign effect, and no high‑accuracy tool provides a definitive pathogenic verdict. Consequently, the variant is most likely pathogenic according to the bulk of predictions, 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.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-4.337	Likely Benign	0.096	Likely Benign	Likely Benign										0.167	Likely Benign	-2.64	Deleterious	0.992	Probably Damaging	0.989	Probably Damaging	2.35	Pathogenic	0.02	Affected			0.4157	0.4207		1	0	2.5	-30.03
c.2425A>G	S809G 2D AIThe SynGAP1 missense variant S809G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the conclusion. Overall, the preponderance of evidence indicates that S809G is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-6.100	Likely Benign	0.142	Likely Benign	Likely Benign										0.085	Likely Benign	-1.80	Neutral	0.270	Benign	0.136	Benign	2.61	Benign	0.02	Affected			0.2743	0.5369		1	0	0.4	-30.03
c.2464A>G	T822A 2D AIThe SynGAP1 T822A missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus (majority vote) remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-3.695	Likely Benign	0.788	Likely Pathogenic	Ambiguous										0.122	Likely Benign	-1.55	Neutral	0.987	Probably Damaging	0.891	Possibly Damaging	2.60	Benign	0.17	Tolerated			0.4566	0.4456		1	0	2.5	-30.03
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.2470A>G	S824G 2D AIThe SynGAP1 missense variant S824G is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33443022‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Based on the preponderance of benign predictions and the consensus from high‑accuracy tools, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750								6-33443022-A-G	1	6.20e-7	-5.476	Likely Benign	0.543	Ambiguous	Likely Benign										0.079	Likely Benign	-1.74	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.60	Benign	0.50	Tolerated	3.77	5	0.2880	0.5437		0	1	0.4	-30.03
c.2482A>G	T828A 2D AIThe SynGAP1 missense variant T828A is reported in gnomAD (variant ID 6‑33443034‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500								6-33443034-A-G	1	6.20e-7	-2.974	Likely Benign	0.340	Likely Benign	Likely Benign										0.197	Likely Benign	-2.13	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.67	Benign	0.24	Tolerated	3.77	5	0.4039	0.3861		0	1	2.5	-30.03
c.2506A>G	S836G 2D AIThe SynGAP1 missense variant S836G is listed in ClinVar (ID 537003.0) with an uncertain significance annotation and is observed in the gnomAD database (variant ID 6‑33443058‑A‑G). Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Benign. Foldetta, a protein‑folding stability predictor, did not return a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports a benign classification, which does not conflict with the ClinVar uncertain designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.634582	Binding	0.269	0.859	0.250					Uncertain		1	6-33443058-A-G	4	2.48e-6	-4.749	Likely Benign	0.112	Likely Benign	Likely Benign										0.066	Likely Benign	-1.65	Neutral	0.006	Benign	0.019	Benign	2.54	Benign	0.39	Tolerated	3.77	5	0.2567	0.4089		1	0	0.4	-30.03
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.253A>G	T85A 2D AIThe SynGAP1 missense variant T85A is not reported in ClinVar and is absent from gnomAD. Consensus and most in‑silico predictors classify it as benign: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM all indicate a benign effect. In contrast, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict a pathogenic impact. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized reports a pathogenic change, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) 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 tools and the consensus prediction lean toward a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-4.803	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.101	Likely Benign	-1.79	Neutral	0.060	Benign	0.004	Benign	3.88	Benign	0.00	Affected			0.3155	0.3517		1	0	2.5	-30.03
c.2569A>G	S857G 2D AIThe SynGAP1 missense variant S857G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for S857G, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.316	Likely Benign	0.067	Likely Benign	Likely Benign										0.124	Likely Benign	-0.57	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	4.10	Benign	0.85	Tolerated			0.2963	0.5644		1	0	0.4	-30.03
c.2572A>G	S858G 2D AIThe SynGAP1 missense variant S858G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumVar indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also predicts benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-2.181	Likely Benign	0.068	Likely Benign	Likely Benign										0.143	Likely Benign	-0.18	Neutral	0.259	Benign	0.786	Possibly Damaging	4.13	Benign	0.11	Tolerated			0.3084	0.5116		1	0	0.4	-30.03
c.2575A>G	S859G 2D AIThe SynGAP1 missense variant S859G is not reported in ClinVar and is absent from gnomAD. In silico predictions cluster into three groups: benign (REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized), pathogenic (polyPhen‑2 HumDiv and HumVar), and uncertain (ESM1b). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for S859G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.412	In-Between	0.087	Likely Benign	Likely Benign										0.118	Likely Benign	-0.69	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	4.00	Benign	0.25	Tolerated			0.2798	0.4988		1	0	0.4	-30.03
c.2617A>G	S873G 2D AIThe SynGAP1 missense variant S873G is catalogued in gnomAD (ID 6‑33443169‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125								6-33443169-A-G	4	2.48e-6	-5.702	Likely Benign	0.219	Likely Benign	Likely Benign										0.120	Likely Benign	-1.88	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.68	Benign	0.75	Tolerated	3.77	5	0.2897	0.5270		0	1	0.4	-30.03
c.2632A>G	T878A 2D AIThe SynGAP1 missense variant T878A is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” and a Foldetta stability analysis is unavailable. Overall, the evidence strongly supports a benign classification, and this does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.628767	Binding	0.288	0.878	0.250					Uncertain		2				-2.154	Likely Benign	0.081	Likely Benign	Likely Benign										0.088	Likely Benign	-0.67	Neutral	0.003	Benign	0.006	Benign	2.73	Benign	0.18	Tolerated	3.77	5	0.4312	0.4625		1	0	2.5	-30.03
c.2683A>G	S895G 2D AIThe SynGAP1 missense variant S895G is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign 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 Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750											-3.728	Likely Benign	0.150	Likely Benign	Likely Benign										0.149	Likely Benign	-1.25	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.67	Benign	0.90	Tolerated			0.2675	0.5087		1	0	0.4	-30.03
c.2698A>G	T900A 2D AIThe SynGAP1 missense variant T900A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.465347	Uncertain	0.289	0.924	0.375											-2.289	Likely Benign	0.081	Likely Benign	Likely Benign										0.028	Likely Benign	-0.49	Neutral	0.059	Benign	0.061	Benign	2.73	Benign	0.40	Tolerated			0.4018	0.4059		1	0	2.5	-30.03
c.2719A>G	S907G 2D AIThe SynGAP1 missense variant S907G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, 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 Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250											-3.018	Likely Benign	0.151	Likely Benign	Likely Benign										0.078	Likely Benign	-1.23	Neutral	0.942	Possibly Damaging	0.788	Possibly Damaging	2.63	Benign	0.04	Affected			0.2625	0.5134		1	0	0.4	-30.03
c.2734A>G	T912A 2D AIThe SynGAP1 missense variant T912A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.740671	Binding	0.285	0.909	0.250											-3.084	Likely Benign	0.097	Likely Benign	Likely Benign										0.088	Likely Benign	-1.50	Neutral	0.973	Probably Damaging	0.856	Possibly Damaging	4.03	Benign	0.00	Affected			0.3754	0.3841		1	0	2.5	-30.03
c.2737A>G	T913A 2D AIThe SynGAP1 missense variant T913A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375											-2.386	Likely Benign	0.083	Likely Benign	Likely Benign										0.098	Likely Benign	-1.41	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.79	Benign	0.15	Tolerated			0.4240	0.4905		1	0	2.5	-30.03
c.2923A>G	T975A 2D AIThe SynGAP1 missense change T975A is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.969331	Binding	0.332	0.890	0.625											-2.866	Likely Benign	0.063	Likely Benign	Likely Benign										0.110	Likely Benign	-0.71	Neutral	0.000	Benign	0.002	Benign	4.19	Benign	0.18	Tolerated			0.3821	0.4275		1	0	2.5	-30.03
c.2947A>G	S983G 2D AIThe SynGAP1 missense variant S983G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are 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, is inconclusive (2 vs 2). High‑accuracy methods show AlphaMissense‑Optimized as benign; the SGM Consensus is unavailable, and Foldetta results are not provided, so no folding‑stability evidence is available. Overall, the balance of evidence (five pathogenic vs four benign predictions) suggests the variant 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.			0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-5.206	Likely Benign	0.638	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-2.22	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.17	Pathogenic	0.00	Affected			0.2521	0.4480		1	0	0.4	-30.03
c.2953A>G	S985G 2D AIThe SynGAP1 missense variant S985G is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). The AlphaMissense‑Default score is uncertain, and Foldetta stability analysis is not available. High‑accuracy assessments show AlphaMissense‑Optimized predicting a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Foldetta, which integrates FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the majority of reliable predictors and the SGM‑Consensus support a benign classification. The variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-6.151	Likely Benign	0.546	Ambiguous	Likely Benign										0.132	Likely Benign	-2.29	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.51	Benign	0.00	Affected			0.2684	0.4540		1	0	0.4	-30.03
c.3007A>G	S1003G 2D AIThe SynGAP1 missense variant S1003G is catalogued in gnomAD (ID 6‑33443559‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for S1003G, 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.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625								6-33443559-A-G	1	6.20e-7	-5.888	Likely Benign	0.542	Ambiguous	Likely Benign										0.088	Likely Benign	-1.72	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.48	Pathogenic	0.00	Affected	3.77	5	0.2730	0.4789		0	1	0.4	-30.03
c.3013A>G	S1005G 2D AIThe SynGAP1 missense change S1005G is catalogued in gnomAD (ID 6‑33443565‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750								6-33443565-A-G			-6.785	Likely Benign	0.537	Ambiguous	Likely Benign										0.095	Likely Benign	-1.98	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.63	Benign	0.00	Affected	3.77	5	0.2328	0.3514		0	1	0.4	-30.03
c.3019A>G	S1007G 2D AIThe SynGAP1 missense variant S1007G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign 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 Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-4.051	Likely Benign	0.297	Likely Benign	Likely Benign										0.098	Likely Benign	-1.49	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.73	Benign	0.05	Affected			0.2361	0.4341		1	0	0.4	-30.03
c.3043A>G	T1015A 2D AIThe SynGAP1 missense variant T1015A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this conclusion does not contradict any ClinVar status (none reported). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.928486	Binding	0.295	0.823	0.625											-2.615	Likely Benign	0.065	Likely Benign	Likely Benign										0.066	Likely Benign	-0.07	Neutral	0.001	Benign	0.002	Benign	2.73	Benign	0.54	Tolerated			0.3960	0.3949		1	0	2.5	-30.03
c.3052A>G	T1018A 2D AIThe SynGAP1 missense variant T1018A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.849326	Disordered	0.959985	Binding	0.348	0.801	0.500											-3.289	Likely Benign	0.087	Likely Benign	Likely Benign										0.082	Likely Benign	-0.55	Neutral	0.001	Benign	0.004	Benign	2.34	Pathogenic	0.53	Tolerated			0.3859	0.3362		1	0	2.5	-30.03
c.3112A>G	T1038A 2D AIThe SynGAP1 missense variant T1038A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, whereas only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.938133	Disordered	0.982911	Binding	0.279	0.794	0.625											-3.544	Likely Benign	0.265	Likely Benign	Likely Benign										0.047	Likely Benign	-0.79	Neutral	0.649	Possibly Damaging	0.209	Benign	2.81	Benign	0.15	Tolerated			0.3429	0.3983		1	0	2.5	-30.03
c.3157A>G	S1053G 2D AIThe SynGAP1 missense variant S1053G is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” 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 strongly suggests that S1053G is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875											-1.016	Likely Benign	0.050	Likely Benign	Likely Benign										0.220	Likely Benign	-0.57	Neutral	0.001	Benign	0.002	Benign	5.32	Benign	0.59	Tolerated			0.2724	0.5046		1	0	0.4	-30.03
c.3169A>G	S1057G 2D AIThe SynGAP1 missense variant S1057G is reported in gnomAD (ID 6‑33443721‑A‑G) but has no ClinVar entry. All evaluated in‑silico predictors uniformly classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, 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 Benign		0.988291	Disordered	0.869507	Binding	0.413	0.927	0.875								6-33443721-A-G	1	7.20e-7	-1.005	Likely Benign	0.049	Likely Benign	Likely Benign										0.211	Likely Benign	-0.47	Neutral	0.421	Benign	0.111	Benign	5.76	Benign	0.52	Tolerated	3.77	5	0.2654	0.4846		0	1	0.4	-30.03
c.3229A>G	T1077A 2D AIThe SynGAP1 missense variant T1077A is catalogued in gnomAD (ID 6‑33443781‑A‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.988141	Binding	0.329	0.892	0.750								6-33443781-A-G			-3.303	Likely Benign	0.280	Likely Benign	Likely Benign										0.153	Likely Benign	-0.60	Neutral	0.288	Benign	0.194	Benign	4.25	Benign	0.10	Tolerated	3.77	5	0.3373	0.4393		0	1	2.5	-30.03
c.3235A>G	S1079G 2D AIThe SynGAP1 missense variant S1079G is reported in gnomAD (variant ID 6‑33443787‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750								6-33443787-A-G	6	3.76e-6	-3.552	Likely Benign	0.177	Likely Benign	Likely Benign										0.065	Likely Benign	-1.50	Neutral	0.036	Benign	0.018	Benign	3.87	Benign	0.00	Affected	3.77	5	0.2151	0.4623		0	1	0.4	-30.03
c.325A>G	S109G 2D AIThe SynGAP1 missense variant S109G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-3.918	Likely Benign	0.549	Ambiguous	Likely Benign										0.132	Likely Benign	-1.95	Neutral	0.378	Benign	0.067	Benign	3.51	Benign	0.00	Affected			0.2686	0.3779		1	0	0.4	-30.03
c.3262A>G	S1088G 2D AIThe SynGAP1 missense variant S1088G is listed in ClinVar (ID 2742833.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as Likely Benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000					Uncertain		1				-5.034	Likely Benign	0.285	Likely Benign	Likely Benign										0.163	Likely Benign	-1.83	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	2.63	Benign	0.03	Affected	3.77	5	0.2541	0.5170		0	1	0.4	-30.03
c.3292A>G	S1098G 2D AIThe SynGAP1 missense variant S1098G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the collective predictions strongly support a benign impact, and this conclusion is consistent with the lack of a ClinVar pathogenic classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.973030	Binding	0.337	0.855	1.000											-3.494	Likely Benign	0.072	Likely Benign	Likely Benign										0.066	Likely Benign	-0.39	Neutral	0.000	Benign	0.001	Benign	2.72	Benign	0.57	Tolerated			0.2634	0.5206		1	0	0.4	-30.03
c.3322A>G	S1108G 2D AIThe SynGAP1 missense variant S1108G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (six benign vs three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.949221	Binding	0.324	0.886	0.875											-6.496	Likely Benign	0.126	Likely Benign	Likely Benign										0.084	Likely Benign	-2.59	Deleterious	0.568	Possibly Damaging	0.239	Benign	2.46	Pathogenic	0.16	Tolerated			0.2268	0.3975		1	0	0.4	-30.03
c.3328A>G	S1110G 2D AIThe SynGAP1 missense variant S1110G is listed in ClinVar (ID 1722210.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.912647	Disordered	0.934156	Binding	0.346	0.892	0.875					Likely Benign		1				-4.674	Likely Benign	0.079	Likely Benign	Likely Benign										0.035	Likely Benign	-2.26	Neutral	0.036	Benign	0.026	Benign	2.19	Pathogenic	0.08	Tolerated	4.32	2	0.2559	0.4806		1	0	0.4	-30.03
c.3340A>G	S1114G 2D AIThe SynGAP1 missense variant S1114G is reported in gnomAD (ID 6‑33443892‑A‑G) but has no ClinVar entry. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, 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 Benign		0.908098	Disordered	0.895196	Binding	0.295	0.908	0.875								6-33443892-A-G			-3.894	Likely Benign	0.064	Likely Benign	Likely Benign										0.080	Likely Benign	-1.33	Neutral	0.000	Benign	0.000	Benign	2.75	Benign	0.08	Tolerated	4.32	2	0.2414	0.4914		0	1	0.4	-30.03
c.3352A>G	S1118G 2D AIThe SynGAP1 missense variant S1118G is reported in gnomAD (ID 6‑33443904‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the preponderance of evidence indicates that S1118G is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750								6-33443904-A-G	1	6.98e-7	-1.615	Likely Benign	0.057	Likely Benign	Likely Benign										0.146	Likely Benign	-0.61	Neutral	0.790	Possibly Damaging	0.433	Benign	5.82	Benign	0.08	Tolerated	4.32	2	0.2737	0.4657		0	1	0.4	-30.03
c.3361A>G	S1121G 2D AIThe SynGAP1 missense variant S1121G is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443913‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, which does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875					Uncertain		1	6-33443913-A-G	1	7.00e-7	-1.220	Likely Benign	0.054	Likely Benign	Likely Benign										0.067	Likely Benign	-0.53	Neutral	0.003	Benign	0.004	Benign	6.63	Benign	0.00	Affected	3.77	5	0.2724	0.4657		0	1	0.4	-30.03
c.3400A>G	T1134A 2D AIThe SynGAP1 missense variant T1134A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion 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 Benign		0.885302	Disordered	0.813034	Binding	0.335	0.885	0.875											-3.912	Likely Benign	0.090	Likely Benign	Likely Benign										0.172	Likely Benign	-0.71	Neutral	0.036	Benign	0.026	Benign	5.70	Benign	0.31	Tolerated			0.3756	0.4424		1	0	2.5	-30.03
c.3418A>G	T1140A 2D AIThe SynGAP1 missense variant T1140A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.708094	Binding	0.293	0.854	1.000											-3.838	Likely Benign	0.107	Likely Benign	Likely Benign										0.061	Likely Benign	-0.36	Neutral	0.002	Benign	0.003	Benign	2.71	Benign	1.00	Tolerated			0.3949	0.3463		1	0	2.5	-30.03
c.3427A>G	T1143A 2D AIThe SynGAP1 missense variant T1143A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of benign predictions and the consensus from high‑accuracy methods, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.722918	Binding	0.275	0.837	1.000											-3.340	Likely Benign	0.159	Likely Benign	Likely Benign										0.061	Likely Benign	-1.19	Neutral	0.877	Possibly Damaging	0.675	Possibly Damaging	2.80	Benign	0.43	Tolerated			0.3252	0.3546		1	0	2.5	-30.03
c.3439A>G	T1147A 2D AIThe SynGAP1 missense variant T1147A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.746520	Binding	0.345	0.839	0.875											-3.115	Likely Benign	0.061	Likely Benign	Likely Benign										0.188	Likely Benign	-1.60	Neutral	0.001	Benign	0.004	Benign	5.54	Benign	0.03	Affected			0.3816	0.3705		1	0	2.5	-30.03
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.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.349A>G	S117G 2D AIThe SynGAP1 missense variant S117G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion 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 Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-3.280	Likely Benign	0.174	Likely Benign	Likely Benign										0.122	Likely Benign	-1.59	Neutral	0.390	Benign	0.066	Benign	3.73	Benign	0.01	Affected			0.2113	0.4627		1	0	0.4	-30.03
c.34A>G	S12G 2D AIThe SynGAP1 missense variant S12G is reported in gnomAD (ID 6‑33420298‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for S12G, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.490599	Uncertain	0.355	0.916	0.500								6-33420298-A-G			-4.229	Likely Benign	0.093	Likely Benign	Likely Benign										0.079	Likely Benign	0.22	Neutral	0.103	Benign	0.015	Benign	4.11	Benign	0.00	Affected	4.32	1	0.2876	0.5080		0	1	0.4	-30.03
c.3508A>G	S1170G 2D AIThe SynGAP1 missense variant S1170G is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500					Uncertain		1				-4.288	Likely Benign	0.221	Likely Benign	Likely Benign										0.349	Likely Benign	-0.81	Neutral	0.241	Benign	0.229	Benign	5.31	Benign	0.54	Tolerated	4.32	4	0.2705	0.4558		1	0	0.4	-30.03
c.3568A>G	S1190G 2D AIThe SynGAP1 missense change S1190G is catalogued in gnomAD (ID 6‑33444603‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) and pathogenic (AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar). High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also favors benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Taken together, the preponderance of evidence points to a benign effect, 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 Benign	Coiled-coil	0.575842	Disordered	0.455760	Uncertain	0.742	0.624	0.625								6-33444603-A-G	1	6.20e-7	-3.078	Likely Benign	0.647	Likely Pathogenic	Likely Benign										0.374	Likely Benign	-1.13	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	5.28	Benign	0.42	Tolerated	3.82	4	0.2312	0.3549		0	1	0.4	-30.03
c.3688A>G	T1230A 2D AIThe SynGAP1 T1230A missense change 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, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy tools—indicates that the variant is most likely benign, and this conclusion is consistent with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.570702	Disordered	0.486342	Uncertain	0.845	0.543	0.250											-5.236	Likely Benign	0.644	Likely Pathogenic	Likely Benign										0.395	Likely Benign	-2.10	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.58	Benign	0.03	Affected			0.2945	0.3231		1	0	2.5	-30.03
c.3691A>G	S1231G 2D AIThe SynGAP1 missense variant S1231G is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. The high‑accuracy consensus, SGM‑Consensus, also reports the variant as Likely Benign, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. AlphaMissense‑Optimized independently 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 evidence strongly supports a benign classification, 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 Benign	Coiled-coil	0.490133	Structured	0.519419	Binding	0.876	0.544	0.250											-5.384	Likely Benign	0.077	Likely Benign	Likely Benign										0.119	Likely Benign	-1.78	Neutral	0.002	Benign	0.005	Benign	2.66	Benign	0.23	Tolerated			0.2247	0.3614		1	0	0.4	-30.03
c.3730A>G	S1244G 2D AIThe SynGAP1 missense variant S1244G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy evidence therefore comes only from AlphaMissense‑Optimized, which predicts benign, while the other high‑accuracy tools are unavailable. Overall, the balance of evidence (five benign vs four pathogenic predictions, with the most reliable tool indicating benign) suggests that the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-8.304	Likely Pathogenic	0.221	Likely Benign	Likely Benign										0.130	Likely Benign	-1.77	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.12	Pathogenic	0.65	Tolerated			0.2267	0.3678		1	0	0.4	-30.03
c.3781A>G	S1261G 2D AIThe SynGAP1 missense variant S1261G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for S1261G, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-5.042	Likely Benign	0.087	Likely Benign	Likely Benign										0.063	Likely Benign	-0.46	Neutral	0.005	Benign	0.013	Benign	2.32	Pathogenic	0.65	Tolerated			0.2063	0.3477		1	0	0.4	-30.03
c.3913A>G	T1305A 2D AIThe SynGAP1 missense variant T1305A is listed in ClinVar (ID 411587.0) with an “Uncertain” clinical significance and is present in the gnomAD database (variant ID 6‑33451787‑A‑G). All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely pathogenic outcome. High‑accuracy assessments reinforce this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.894658	Binding	0.390	0.873	0.875					Conflicting		4	6-33451787-A-G	30	1.86e-5	-2.692	Likely Benign	0.055	Likely Benign	Likely Benign										0.069	Likely Benign	1.74	Neutral	0.000	Benign	0.001	Benign	3.24	Benign	1.00	Tolerated	3.77	5	0.4533	0.4746		1	0	2.5	-30.03
c.3928A>G	T1310A 2D AIThe SynGAP1 missense variant T1310A is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, 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 Benign		0.812494	Disordered	0.959076	Binding	0.398	0.904	0.750											-2.883	Likely Benign	0.070	Likely Benign	Likely Benign										0.084	Likely Benign	-0.21	Neutral	0.041	Benign	0.039	Benign	2.83	Benign	0.13	Tolerated			0.3238	0.3177		1	0	2.5	-30.03
c.3943T>A	W1315R 2D AIThe SynGAP1 missense variant W1315R is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. Only AlphaMissense‑Default predicts a pathogenic outcome, representing the sole discordant signal. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools points to a benign effect, 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 Benign		0.885302	Disordered	0.973142	Binding	0.403	0.889	0.750											0.205	Likely Benign	0.660	Likely Pathogenic	Likely Benign										0.114	Likely Benign	1.31	Neutral	0.000	Benign	0.001	Benign	4.37	Benign	0.91	Tolerated	3.77	5	0.4317	0.0384		2	-3	-3.6	-30.03
c.3943T>C	W1315R 2D AIThe SynGAP1 missense variant W1315R is listed in ClinVar (ID 1029092.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.973142	Binding	0.403	0.889	0.750					Uncertain		1				0.205	Likely Benign	0.660	Likely Pathogenic	Likely Benign										0.114	Likely Benign	1.31	Neutral	0.000	Benign	0.001	Benign	4.37	Benign	0.91	Tolerated	3.77	5	0.4317	0.0384		2	-3	-3.6	-30.03
c.3994A>G	T1332A 2D AIThe SynGAP1 missense variant T1332A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of available predictions (five 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.			0.915074	Disordered	0.948427	Binding	0.442	0.754	0.875											-3.521	Likely Benign	0.887	Likely Pathogenic	Ambiguous										0.150	Likely Benign	-2.85	Deleterious	0.953	Possibly Damaging	0.935	Probably Damaging	3.02	Benign	0.00	Affected			0.4042	0.4766		1	0	2.5	-30.03
c.400A>G	S134G 2D AIThe SynGAP1 missense variant S134G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized also reports a benign prediction. 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 and the high‑accuracy consensus indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-6.722	Likely Benign	0.457	Ambiguous	Likely Benign										0.120	Likely Benign	-2.19	Neutral	0.034	Benign	0.035	Benign	3.84	Benign	0.00	Affected			0.2268	0.4008		1	0	0.4	-30.03
c.4018A>G	T1340A 2D AIThe SynGAP1 missense variant T1340A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, supports a benign classification. This prediction is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.977899	Binding	0.444	0.697	0.750											-3.192	Likely Benign	0.078	Likely Benign	Likely Benign										0.116	Likely Benign	-1.01	Neutral	0.010	Benign	0.011	Benign	4.20	Benign	0.02	Affected			0.3984	0.4288		1	0	2.5	-30.03
c.415A>G	S139G 2D AIThe SynGAP1 missense variant S139G is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus, also reports the variant as Likely Benign, and AlphaMissense‑Optimized confirms a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.553315	Disordered	0.600637	Binding	0.353	0.900	0.250											1.647	Likely Benign	0.159	Likely Benign	Likely Benign										0.116	Likely Benign	1.29	Neutral	0.000	Benign	0.000	Benign	4.29	Benign	1.00	Tolerated			0.2712	0.3414		1	0	0.4	-30.03
c.430A>G	T144A 2D AIThe SynGAP1 missense variant T144A 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 REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-4.007	Likely Benign	0.440	Ambiguous	Likely Benign										0.065	Likely Benign	-2.24	Neutral	0.000	Benign	0.001	Benign	3.95	Benign	0.00	Affected			0.4777	0.4131		1	0	2.5	-30.03
c.457A>G	T153A 2D AIThe SynGAP1 missense variant T153A is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, 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 Benign		0.501700	Disordered	0.502105	Binding	0.297	0.818	0.625											-3.016	Likely Benign	0.234	Likely Benign	Likely Benign										0.173	Likely Benign	-1.54	Neutral	0.620	Possibly Damaging	0.220	Benign	4.15	Benign	0.05	Affected			0.4430	0.2985		1	0	2.5	-30.03
c.460A>G	S154G 2D AIThe SynGAP1 missense variant S154G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, 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 Benign		0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-5.482	Likely Benign	0.115	Likely Benign	Likely Benign										0.074	Likely Benign	-0.83	Neutral	0.006	Benign	0.008	Benign	4.05	Benign	0.11	Tolerated			0.2790	0.3944		1	0	0.4	-30.03
c.463A>G	S155G 2D AIThe SynGAP1 missense variant S155G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically indicate a benign outcome from AlphaMissense‑Optimized, while SGM Consensus and Foldetta are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-9.243	Likely Pathogenic	0.628	Likely Pathogenic	Likely Benign										0.152	Likely Benign	-1.84	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.81	Benign	0.00	Affected			0.2416	0.3976		1	0	0.4	-30.03
c.493A>G	S165G 2D AIThe SynGAP1 missense variant S165G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-7.691	In-Between	0.223	Likely Benign	Likely Benign										0.182	Likely Benign	-1.17	Neutral	0.272	Benign	0.086	Benign	3.99	Benign	0.00	Affected			0.2622	0.4441		1	0	0.4	-30.03
c.4A>G	S2G 2D AIThe SynGAP1 missense variant S2G is reported in gnomAD (ID 6‑33420268‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for this variant, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.543646	Binding	0.382	0.922	0.750								6-33420268-A-G	1	6.58e-7	-4.273	Likely Benign	0.124	Likely Benign	Likely Benign										0.079	Likely Benign	-0.48	Neutral	0.012	Benign	0.002	Benign	4.10	Benign	0.00	Affected	4.32	1	0.2872	0.5495		0	1	0.4	-30.03
c.526A>G	S176G 2D AIThe SynGAP1 missense variant S176G is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33435168‑A‑G). Consensus among most in silico predictors is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all report a benign effect. No tool predicts pathogenicity. Two predictors are inconclusive: ESM1b and AlphaMissense‑Default, which are grouped under uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains uncertain, and Foldetta stability analysis is unavailable. Overall, the computational evidence overwhelmingly favors a benign impact, which does not contradict the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.466016	Uncertain	0.380	0.597	0.375					Uncertain		1	6-33435168-A-G	1	6.20e-7	-7.541	In-Between	0.360	Ambiguous	Likely Benign										0.066	Likely Benign	-1.08	Neutral	0.131	Benign	0.039	Benign	4.08	Benign	0.22	Tolerated	3.54	6	0.2361	0.3414		0	1	0.4	-30.03
c.562A>G	S188G 2D AIThe SynGAP1 missense variant S188G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is “Likely Pathogenic.” AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.113	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-3.10	Deleterious	0.882	Possibly Damaging	0.404	Benign	3.91	Benign	0.00	Affected			0.3045	0.5542		1	0	0.4	-30.03
c.568A>G	S190G 2D AIThe SynGAP1 missense variant S190G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250											-5.440	Likely Benign	0.321	Likely Benign	Likely Benign										0.048	Likely Benign	-1.26	Neutral	0.243	Benign	0.079	Benign	4.11	Benign	0.19	Tolerated			0.2780	0.4765		1	0	0.4	-30.03
c.571A>G	S191G 2D AIThe SynGAP1 missense variant S191G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also leans toward benign (two benign versus two uncertain). 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 S191G is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.161	In-Between	0.506	Ambiguous	Likely Benign										0.173	Likely Benign	-2.43	Neutral	0.131	Benign	0.058	Benign	3.77	Benign	0.03	Affected			0.2893	0.5335		1	0	0.4	-30.03
c.631A>G	S211G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, and ESM1b; Rosetta is uncertain. High‑accuracy methods give a benign result for AlphaMissense‑Optimized and for Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs two pathogenic). No evidence from ClinVar contradicts these predictions. Overall, the balance of evidence—including the unanimous benign calls from the high‑accuracy tools—suggests that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-9.895	Likely Pathogenic	0.265	Likely Benign	Likely Benign	0.30	Likely Benign	0.2	0.54	Ambiguous	0.42	Likely Benign	1.07	Destabilizing	0.067	Likely Benign	-3.17	Deleterious	0.787	Possibly Damaging	0.404	Benign	3.92	Benign	0.07	Tolerated			0.2560	0.4337		1	0	0.4	-30.03
c.667A>G	T223A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T223A is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33435518‑A‑G). Functional prediction tools that agree on a benign effect include FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL and PROVEAN. Predictions that are inconclusive are Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also resolves to benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.070400	Structured	0.382605	Uncertain	0.867	0.316	0.125					Uncertain		1	6-33435518-A-G	3	1.86e-6	-7.076	In-Between	0.316	Likely Benign	Likely Benign	0.30	Likely Benign	0.1	0.77	Ambiguous	0.54	Ambiguous	0.74	Ambiguous	0.574	Likely Pathogenic	-3.36	Deleterious	0.231	Benign	0.058	Benign	5.74	Benign	0.09	Tolerated	3.41	13	0.2982	0.3031		1	0	2.5	-30.03	186.4	44.0	0.0	0.0	0.0	0.0	X	X						Uncertain	The introduced residue Ala223 is located on the outer surface of an anti-parallel β sheet strand (res. Cys219-Thr224). Unlike the hydroxyl group of the Thr223 side chain in the WT protein, the methyl side chain of Ala223 cannot form hydrogen bonds with nearby residues Thr228 and Lys207. Without these hydrogen-bonding interactions at the β sheet surface, the secondary structure element becomes unstable and partially unfolds in the variant simulations. However, since the model ends abruptly at the N-terminus, no definite conclusions can be drawn from the simulations.
c.670A>G	T224A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T224A is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33435521‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and AlphaMissense‑Default. The remaining tools (Rosetta, Foldetta, premPS, ESM1b) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.104810	Structured	0.360921	Uncertain	0.848	0.315	0.125					Uncertain		3	6-33435521-A-G	2	1.24e-6	-7.379	In-Between	0.651	Likely Pathogenic	Likely Benign	0.33	Likely Benign	0.1	1.05	Ambiguous	0.69	Ambiguous	0.91	Ambiguous	0.464	Likely Benign	-2.96	Deleterious	0.243	Benign	0.079	Benign	5.57	Benign	0.57	Tolerated	3.41	13	0.4253	0.5053		1	0	2.5	-30.03	169.0	41.4	-0.5	1.1	-0.4	0.0	X	X						Uncertain	The introduced residue Ala224 is located on the outer surface of an anti-parallel β sheet strand (res. Cys219-Thr224). Unlike the hydroxyl group of the Thr224 side chain in the WT model, the methyl side chain of Ala224 cannot form hydrogen bonds with nearby residues Ser204, Ser226, and Gly227. Without these hydrogen-bonding interactions at the β sheet surface, the secondary structure element becomes unstable and unfolds during the variant simulations. However, since the model ends abruptly at the N-terminus, no definite conclusions can be drawn from the simulations.
c.682A>G	T228A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T228A variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score (which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are REVEL, SIFT, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as benign (majority of its constituent predictors are benign), and Foldetta as uncertain. Overall, the balance of evidence favors a benign interpretation; this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-5.190	Likely Benign	0.793	Likely Pathogenic	Ambiguous	0.44	Likely Benign	0.0	0.82	Ambiguous	0.63	Ambiguous	0.58	Ambiguous	0.520	Likely Pathogenic	-2.30	Neutral	0.363	Benign	0.138	Benign	5.63	Benign	0.04	Affected			0.4072	0.5014		1	0	2.5	-30.03
c.724T>A	W242R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant W242R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess evolutionary conservation and protein function uniformly indicate a deleterious effect: REVEL, premPS, 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 only inconclusive results come from FoldX, Rosetta, and Foldetta, which are treated as unavailable evidence. 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 remains uncertain. Consequently, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.328603	Structured	0.352582	Uncertain	0.847	0.341	0.000											-11.948	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.85	Ambiguous	0.5	1.15	Ambiguous	1.00	Ambiguous	1.34	Destabilizing	0.859	Likely Pathogenic	-12.71	Deleterious	0.995	Probably Damaging	0.854	Possibly Damaging	1.52	Pathogenic	0.00	Affected	3.40	14	0.4206	0.0771		-3	2	-3.6	-30.03
c.724T>C	W242R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W242R is reported in gnomAD (ID 6‑33435575‑T‑C) but has no ClinVar entry. Across the evaluated predictors, every tool that provides a definitive call classifies the substitution as pathogenic: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No predictor reports a benign effect. FoldX, Rosetta, and Foldetta return uncertain results and are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, while Foldetta remains inconclusive. Consequently, the variant is most likely pathogenic based on the consensus of pathogenic predictions, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.328603	Structured	0.352582	Uncertain	0.847	0.341	0.000								6-33435575-T-C	2	1.24e-6	-11.948	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.85	Ambiguous	0.5	1.15	Ambiguous	1.00	Ambiguous	1.34	Destabilizing	0.858	Likely Pathogenic	-12.71	Deleterious	0.995	Probably Damaging	0.854	Possibly Damaging	1.52	Pathogenic	0.00	Affected	3.40	14	0.4206	0.0771		-3	2	-3.6	-30.03
c.769A>G	S257G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S257G is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD status: None). Prediction tools that agree on a benign effect include SIFT, FATHMM, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates a benign change, whereas the SGM‑Consensus (majority vote) indicates likely pathogenic. The Foldetta stability prediction is unavailable and therefore does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the lack of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.258293	Uncertain	0.847	0.272	0.250											-11.206	Likely Pathogenic	0.624	Likely Pathogenic	Likely Benign	0.61	Ambiguous	0.3	0.60	Ambiguous	0.61	Ambiguous	0.62	Ambiguous	0.703	Likely Pathogenic	-2.95	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	5.79	Benign	0.11	Tolerated			0.2087	0.3589		1	0	0.4	-30.03
c.799T>A	W267R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W267R has no ClinVar entry and is not reported in gnomAD. Prediction tools that assess pathogenicity all agree on a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return pathogenic or likely pathogenic scores. Tools that are inconclusive (FoldX and premPS) are noted as uncertain. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No benign predictions are present. Consequently, 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	C2	0.216401	Structured	0.298060	Uncertain	0.943	0.274	0.000											-13.868	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.94	Ambiguous	0.1	2.47	Destabilizing	2.21	Destabilizing	0.51	Ambiguous	0.672	Likely Pathogenic	-12.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.00	Pathogenic	0.01	Affected			0.3763	0.0571		2	-3	-3.6	-30.03
c.799T>C	W267R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W267R is not reported in ClinVar (ClinVar status: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tools predict a benign outcome. Uncertain predictions are provided by FoldX and premPS. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic; and Foldetta predicts Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.298060	Uncertain	0.943	0.274	0.000											-13.868	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.94	Ambiguous	0.1	2.47	Destabilizing	2.21	Destabilizing	0.51	Ambiguous	0.672	Likely Pathogenic	-12.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.00	Pathogenic	0.01	Affected			0.3763	0.0571		2	-3	-3.6	-30.03
c.880A>G	T294A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T294A missense variant is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain call is FoldX. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic, and Foldetta predicts Pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.316932	Uncertain	0.919	0.267	0.125											-12.371	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	2.27	Destabilizing	2.07	Destabilizing	1.05	Destabilizing	0.719	Likely Pathogenic	-4.60	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	-0.18	Pathogenic	0.03	Affected			0.3687	0.3494		1	0	2.5	-30.03
c.883A>G	T295A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T295A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into benign (REVEL, FoldX, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM). Four tools are uncertain (Rosetta, Foldetta, premPS, ESM1b). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the majority of conventional predictors lean toward a benign effect, whereas the SGM Consensus indicates a pathogenic signal. Thus, the variant is most likely benign based on the bulk of evidence, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125											-7.276	In-Between	0.336	Likely Benign	Likely Benign	0.22	Likely Benign	0.1	1.17	Ambiguous	0.70	Ambiguous	0.56	Ambiguous	0.340	Likely Benign	-3.51	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.96	Pathogenic	0.11	Tolerated			0.4623	0.4190		1	0	2.5	-30.03
c.913A>G	T305A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T305A variant is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33437818‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.359901	Structured	0.299706	Uncertain	0.872	0.274	0.125					Conflicting		2	6-33437818-A-G	13	8.05e-6	-4.307	Likely Benign	0.078	Likely Benign	Likely Benign	1.30	Ambiguous	0.6	1.55	Ambiguous	1.43	Ambiguous	0.77	Ambiguous	0.144	Likely Benign	-2.10	Neutral	0.939	Possibly Damaging	0.645	Possibly Damaging	1.76	Pathogenic	0.12	Tolerated	3.40	20	0.4277	0.4403		1	0	2.5	-30.03	177.9	43.5	-0.2	0.1	0.4	0.0								Uncertain	The hydroxyl group of Thr305, located at the beginning of an anti-parallel β strand (res. Thr305-Asn315), hydrogen bonds with the carboxylate groups of Glu270 and Asp304 in the anti-parallel β strand and the adjacent β hairpin loop, respectively. In the variant simulations, the methyl group of the Ala305 side chain cannot hydrogen bond with either of the acidic residues, which could weaken the integrity of the tertiary structure and the β hairpin loop. Indeed, the guanidinium group of Arg299 does not acquire its central hairpin loop position due to the residue swap.β hairpins are potential nucleation sites during the initial stages of protein folding, so even minor changes in them could be significant. Due to its location near the membrane surface, the residue swap could also affect the C2 loop dynamics and SynGAP-membrane association. However, this is beyond the scope of the solvent-only simulations to unravel.
c.922T>A	W308R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W308R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the consensus of all available predictions, the variant is most likely pathogenic, 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	C2	0.328603	Structured	0.333942	Uncertain	0.907	0.314	0.125											-12.264	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.40	Destabilizing	0.5	4.27	Destabilizing	4.84	Destabilizing	1.88	Destabilizing	0.868	Likely Pathogenic	-12.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.48	Pathogenic	0.00	Affected	3.38	19	0.4751	0.0361		2	-3	-3.6	-30.03	290.4	-26.7	-0.1	0.1	0.0	0.2	X		X				X	Potentially Pathogenic	The indole ring of Trp308, located in an anti-parallel β sheet strand (res. Thr305-Asn315), packs against multiple hydrophobic residues (e.g., Ile268, Val306, Cys282). The indole group of Trp308 also hydrogen bonds with the backbone atoms of the C2 domain residues forming the anti-parallel β sheet (e.g., Tyr280, Thr294). The guanidinium group of Arg308 is comparably sized to the tryptophan it replaced; however, it is also positively charged.In the variant simulations, the charged side chain remains buried deep in the hydrophobic part of the C2 domain, where it forms new hydrogen bonds with the backbone carbonyl atoms of surrounding residues (e.g., Val306, Ile268). However, the residue swap is likely to disrupt the hydrophobic packing during folding. At a minimum, the residue swap could affect the C2 domain stability and membrane association.
c.922T>C	W308R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W308R is listed in ClinVar (ID 391294.0) as Pathogenic and is not reported in gnomAD. All available in‑silico predictors classify the change as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.333942	Uncertain	0.907	0.314	0.125					Pathogenic		1				-12.264	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	5.40	Destabilizing	0.5	4.27	Destabilizing	4.84	Destabilizing	1.88	Destabilizing	0.868	Likely Pathogenic	-12.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.48	Pathogenic	0.00	Affected	3.38	19	0.4751	0.0361		2	-3	-3.6	-30.03	290.4	-26.7	-0.1	0.1	0.0	0.2	X		X				X	Potentially Pathogenic	The indole ring of Trp308, located in an anti-parallel β sheet strand (res. Thr305-Asn315), packs against multiple hydrophobic residues (e.g., Ile268, Val306, Cys282). The indole group of Trp308 also hydrogen bonds with the backbone atoms of the C2 domain residues forming the anti-parallel β sheet (e.g., Tyr280, Thr294). The guanidinium group of Arg308 is comparably sized to the tryptophan it replaced; however, it is also positively charged.In the variant simulations, the charged side chain remains buried deep in the hydrophobic part of the C2 domain, where it forms new hydrogen bonds with the backbone carbonyl atoms of surrounding residues (e.g., Val306, Ile268). However, the residue swap is likely to disrupt the hydrophobic packing during folding. At a minimum, the residue swap could affect the C2 domain stability and membrane association.
c.94A>G	T32A 2D AIThe SynGAP1 missense variant T32A is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign 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 Benign		0.707965	Disordered	0.437154	Uncertain	0.349	0.879	0.375											-3.330	Likely Benign	0.072	Likely Benign	Likely Benign										0.047	Likely Benign	-0.63	Neutral	0.043	Benign	0.016	Benign	4.21	Benign	0.00	Affected			0.4174	0.4742		1	0	2.5	-30.03
c.1079A>T	E360V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the overwhelming majority of reliable predictors classify E360V as pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-14.388	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.11	Ambiguous	1.06	Ambiguous	0.03	Likely Benign	0.627	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	1.57	Pathogenic	0.00	Affected			0.1143	0.8670		-2	-2	7.7	-29.98
c.1244A>T	E415V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415V missense variant is not reported in ClinVar or gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts benign. No evidence is missing or inconclusive. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-11.182	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.56	Ambiguous	0.2	0.14	Likely Benign	0.35	Likely Benign	0.40	Likely Benign	0.441	Likely Benign	-6.52	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.13	Benign	0.02	Affected			0.0650	0.4218		-2	-2	7.7	-29.98
c.1256A>T	E419V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, FATHMM, and premPS, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from the high‑accuracy tools contradicts the pathogenic prediction. Overall, the majority of computational evidence points to a pathogenic effect, which is consistent with the lack of ClinVar reporting and gnomAD absence, suggesting the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-12.290	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.45	Likely Benign	0.0	1.41	Ambiguous	0.93	Ambiguous	0.27	Likely Benign	0.494	Likely Benign	-6.55	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.35	Benign	0.01	Affected			0.0953	0.6834		-2	-2	7.7	-29.98
c.1265A>T	E422V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E422V 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, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a likely pathogenic outcome, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign effect. FoldX remains uncertain. Overall, the majority of high‑confidence tools 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	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-12.371	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.90	Ambiguous	0.1	-0.02	Likely Benign	0.44	Likely Benign	0.24	Likely Benign	0.489	Likely Benign	-6.38	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.29	Benign	0.00	Affected			0.0609	0.5457		-2	-2	7.7	-29.98
c.1307A>T	E436V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436V variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include premPS and FATHMM, while the remaining evaluated algorithms (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. 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 any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-13.364	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.45	Ambiguous	0.0	1.62	Ambiguous	1.54	Ambiguous	0.30	Likely Benign	0.875	Likely Pathogenic	-6.63	Deleterious	0.995	Probably Damaging	0.967	Probably Damaging	4.64	Benign	0.03	Affected			0.0727	0.5952		-2	-2	7.7	-29.98
c.1334A>T	E445V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E445V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points toward a pathogenic effect. The variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-14.830	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	-0.67	Ambiguous	-0.17	Likely Benign	0.32	Likely Benign	0.572	Likely Pathogenic	-6.68	Deleterious	0.992	Probably Damaging	0.967	Probably Damaging	3.34	Benign	0.01	Affected			0.0414	0.5233		-2	-2	7.7	-29.98
c.1337A>T	E446V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E446V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta, premPS, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive 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 as uncertain. Overall, the majority of evaluated tools (8 pathogenic vs. 3 benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-12.231	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	1.72	Ambiguous	0.7	0.34	Likely Benign	1.03	Ambiguous	0.37	Likely Benign	0.513	Likely Pathogenic	-6.55	Deleterious	0.995	Probably Damaging	0.983	Probably Damaging	3.19	Benign	0.00	Affected			0.0618	0.6433		-2	-2	7.7	-29.98
c.1415A>T	E472V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E472V 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 Foldetta and premPS, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. No prediction or folding‑stability result is missing or inconclusive; uncertain outputs from FoldX and Rosetta are treated as unavailable. Overall, the majority of evidence points to a pathogenic effect, 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	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-14.957	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	1.05	Ambiguous	0.3	-0.64	Ambiguous	0.21	Likely Benign	0.37	Likely Benign	0.733	Likely Pathogenic	-6.90	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.0881	0.6347		-2	-2	7.7	-29.98
c.1433A>T	E478V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E478V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, Rosetta, polyPhen‑2 (HumDiv and HumVar), FATHMM, and premPS; pathogenic predictions from SGM‑Consensus, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: FoldX (uncertain) and AlphaMissense‑Optimized (uncertain). High‑accuracy assessments further split the signal: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. With six benign versus five pathogenic calls and no ClinVar evidence, the overall evidence slightly favors a benign interpretation, and there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000											-10.322	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	0.33	Likely Benign	0.44	Likely Benign	0.04	Likely Benign	0.385	Likely Benign	-5.84	Deleterious	0.434	Benign	0.199	Benign	3.35	Benign	0.01	Affected			0.0586	0.6604		-2	-2	7.7	-29.98
c.1439A>T	E480V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E480V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only premPS. All other evaluated algorithms—REVEL, 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. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the overwhelming majority of predictions support a pathogenic effect for E480V. 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	GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-12.347	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.94	Ambiguous	0.1	0.74	Ambiguous	0.84	Ambiguous	0.31	Likely Benign	0.797	Likely Pathogenic	-6.07	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	-1.24	Pathogenic	0.02	Affected			0.0496	0.7192		-2	-2	7.7	-29.98
c.1457A>T	E486V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, SIFT, FATHMM, and Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Uncertain results from FoldX and Rosetta are treated as unavailable. Overall, the majority of predictions support a pathogenic classification, and this conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-15.115	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.54	Ambiguous	0.1	-0.65	Ambiguous	-0.06	Likely Benign	0.31	Likely Benign	0.490	Likely Benign	-6.36	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.37	Benign	0.06	Tolerated			0.0493	0.6445		-2	-2	7.7	-29.98
c.1484A>T	E495V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E495V is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as benign. Taken together, the preponderance of evidence (10 pathogenic‑predicted tools versus 4 benign) indicates that E495V is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000											-12.031	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.43	Likely Benign	0.2	-0.32	Likely Benign	0.06	Likely Benign	0.47	Likely Benign	0.887	Likely Pathogenic	-6.83	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.44	Pathogenic	0.00	Affected			0.0646	0.5457		-2	-2	7.7	-29.98
c.1487A>T	E496V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E496V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Foldetta, and premPS, while pathogenic calls are made by REVEL, PROVEAN, 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 give mixed results: AlphaMissense‑Optimized is Uncertain; SGM‑Consensus remains Likely Pathogenic; Foldetta, a folding‑stability predictor that integrates FoldX‑MD and Rosetta outputs, classifies the variant as Benign. Because the variant is not present in ClinVar, there is no clinical annotation to contradict the computational evidence. Overall, the preponderance of pathogenic predictions, including the consensus score, suggests that E496V is most likely pathogenic, though the conflicting high‑accuracy folding stability result indicates uncertainty that warrants further functional validation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000											-14.290	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.1	-0.67	Ambiguous	-0.25	Likely Benign	0.26	Likely Benign	0.823	Likely Pathogenic	-6.16	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.43	Pathogenic	0.02	Affected			0.0556	0.3746		-2	-2	7.7	-29.98
c.1535A>T	E512V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-14.011	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous	0.72	Ambiguous	0.1	1.00	Ambiguous	0.86	Ambiguous	0.14	Likely Benign	0.439	Likely Benign	-6.71	Deleterious	0.989	Probably Damaging	0.854	Possibly Damaging	3.23	Benign	0.01	Affected			0.0994	0.4884		-2	-2	7.7	-29.98
c.1556A>T	E519V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight the discord: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates benign stability. Overall, the preponderance of evidence points to a pathogenic effect for E519V. This conclusion does not conflict with ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-10.513	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.59	Ambiguous	0.0	-0.40	Likely Benign	0.10	Likely Benign	0.16	Likely Benign	0.400	Likely Benign	-6.33	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	3.20	Benign	0.00	Affected			0.0825	0.4369		-2	-2	7.7	-29.98
c.1562A>T	E521V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact for E521V, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-10.297	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.49	Likely Benign	0.40	Likely Benign	0.21	Likely Benign	0.413	Likely Benign	-5.15	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.05	Affected			0.0913	0.7104		-2	-2	7.7	-29.98
c.1565A>T	E522V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a pathogenic effect, 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	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-11.985	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.09	Likely Benign	0.2	0.00	Likely Benign	0.05	Likely Benign	0.18	Likely Benign	0.751	Likely Pathogenic	-6.59	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	-1.31	Pathogenic	0.01	Affected			0.0537	0.4514		-2	-2	7.7	-29.98
c.1574A>T	E525V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E525V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Foldetta, premPS, and FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome; FoldX and Rosetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for E525V, 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	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-13.622	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	1.10	Ambiguous	0.7	-0.69	Ambiguous	0.21	Likely Benign	0.00	Likely Benign	0.683	Likely Pathogenic	-6.96	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	2.66	Benign	0.00	Affected			0.0721	0.4946		-2	-2	7.7	-29.98
c.1613A>T	E538V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E538V missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, Rosetta, Foldetta, premPS, and FATHMM. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of evidence points to a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-11.537	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.67	Ambiguous	0.0	-0.49	Likely Benign	0.09	Likely Benign	0.23	Likely Benign	0.310	Likely Benign	-5.53	Deleterious	0.929	Possibly Damaging	0.641	Possibly Damaging	3.30	Benign	0.04	Affected			0.0722	0.4436		-2	-2	7.7	-29.98
c.1643A>T	E548V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548V missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM. In contrast, tools predicting a pathogenic impact are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10 pathogenic vs. 5 benign) support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000											-15.029	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.0	-0.18	Likely Benign	0.06	Likely Benign	0.36	Likely Benign	0.578	Likely Pathogenic	-6.83	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.24	Benign	0.02	Affected			0.0569	0.4714		-2	-2	7.7	-29.98
c.1691A>T	E564V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on benign effect include premPS and SIFT, whereas the majority of algorithms—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E564V, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-15.163	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.53	Ambiguous	0.0	0.75	Ambiguous	0.64	Ambiguous	0.23	Likely Benign	0.812	Likely Pathogenic	-6.90	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	-1.37	Pathogenic	0.11	Tolerated			0.0571	0.5503		-2	-2	7.7	-29.98
c.1700A>T	E567V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E567V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Rosetta alone is inconclusive and treated as unavailable. Overall, the majority of evidence points to a pathogenic effect for E567V, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-15.638	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.1	0.59	Ambiguous	0.43	Likely Benign	0.38	Likely Benign	0.440	Likely Benign	-6.77	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.06	Tolerated			0.0573	0.6175		-2	-2	7.7	-29.98
c.1733A>T	E578V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E578V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors cluster into two groups: benign predictions come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: FoldX and AlphaMissense‑Optimized. High‑accuracy assessments further show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence favors a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-11.393	Likely Pathogenic	0.881	Likely Pathogenic	Ambiguous	0.72	Ambiguous	0.1	0.02	Likely Benign	0.37	Likely Benign	0.12	Likely Benign	0.607	Likely Pathogenic	-3.74	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	-1.43	Pathogenic	0.13	Tolerated			0.0575	0.5703		-2	-2	7.7	-29.98
c.1745A>T	E582V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E582V is not reported in ClinVar and is absent from gnomAD. Computational predictors show a split: benign calls from REVEL, Rosetta, premPS, SIFT, and FATHMM; pathogenic calls from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; and two uncertain calls from FoldX and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic consensus: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain due to conflicting inputs. Overall, the computational evidence leans toward pathogenicity, and this assessment does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-10.737	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.87	Ambiguous	0.1	-0.13	Likely Benign	0.37	Likely Benign	0.24	Likely Benign	0.251	Likely Benign	-3.92	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.15	Benign	0.10	Tolerated			0.0564	0.4186		-2	-2	7.7	-29.98
c.182A>T	E61V 2D AIThe SynGAP1 E61V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict the ClinVar status, which currently has no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.352862	Structured	0.477329	Uncertain	0.518	0.699	0.125											-5.723	Likely Benign	0.769	Likely Pathogenic	Likely Benign										0.115	Likely Benign	-1.80	Neutral	0.824	Possibly Damaging	0.775	Possibly Damaging	4.07	Benign	0.00	Affected			0.0803	0.6413		-2	-2	7.7	-29.98
c.1838A>T	E613V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E613V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are Foldetta and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. FoldX and Rosetta give uncertain results and are not included in the agreement groups. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Because the majority of evidence points to a deleterious effect, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-12.799	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.5	-0.76	Ambiguous	-0.02	Likely Benign	0.31	Likely Benign	0.767	Likely Pathogenic	-6.57	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	-1.25	Pathogenic	0.03	Affected			0.0935	0.6565		-2	-2	7.7	-29.98
c.1850A>T	E617V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617V has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into benign (premPS, SIFT) and pathogenic (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default). Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic, while AlphaMissense‑Optimized remains uncertain and Foldetta is also uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E617V. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000											-10.826	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.60	Ambiguous	0.1	0.92	Ambiguous	0.76	Ambiguous	0.28	Likely Benign	0.816	Likely Pathogenic	-5.71	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	-1.47	Pathogenic	0.13	Tolerated			0.0587	0.6503		-2	-2	7.7	-29.98
c.188A>T	E63V 2D AIThe SynGAP1 E63V missense variant has no ClinVar record and is not present in gnomAD. Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. AlphaMissense‑Optimized returns an Uncertain result, and no Foldetta stability data are available. Overall, the balance of evidence leans toward a benign effect, with several high‑confidence predictors supporting pathogenicity, leaving the assessment inconclusive. The predictions do not contradict any ClinVar status, as none is assigned. Based on the aggregate predictions, the variant is most likely benign, and this is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125											-3.588	Likely Benign	0.921	Likely Pathogenic	Ambiguous										0.143	Likely Benign	-2.15	Neutral	0.824	Possibly Damaging	0.775	Possibly Damaging	3.85	Benign	0.00	Affected			0.0559	0.7584		-2	-2	7.7	-29.98
c.1928A>T	E643V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E643V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from Rosetta, premPS, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Three tools (FoldX, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show that the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic (3 pathogenic vs. 1 benign). AlphaMissense‑Optimized remains uncertain, and Foldetta also yields an uncertain stability change. Overall, the preponderance of evidence points to a pathogenic effect for E643V, 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	GAP	0.033407	Structured	0.215915	Uncertain	0.871	0.315	0.000											-12.975	Likely Pathogenic	0.893	Likely Pathogenic	Ambiguous	1.13	Ambiguous	0.1	-0.06	Likely Benign	0.54	Ambiguous	-0.28	Likely Benign	0.554	Likely Pathogenic	-6.85	Deleterious	0.727	Possibly Damaging	0.145	Benign	2.89	Benign	0.00	Affected			0.0948	0.6637		-2	-2	7.7	-29.98
c.1952A>T	E651V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E651V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools split in their assessment: benign‑predicted scores include REVEL, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic‑predicted scores come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX give uncertain results. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, leans pathogenic (3 pathogenic vs. 1 benign); Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the majority of tools (including the high‑accuracy SGM Consensus) suggest a pathogenic impact, whereas Foldetta and several other predictors indicate benign. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-10.025	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous	0.63	Ambiguous	0.1	0.25	Likely Benign	0.44	Likely Benign	0.21	Likely Benign	0.467	Likely Benign	-5.53	Deleterious	0.988	Probably Damaging	0.734	Possibly Damaging	3.27	Benign	0.05	Affected			0.0824	0.6136		-2	-2	7.7	-29.98
c.1961A>T	E654V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E654V missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the majority of tools (8 pathogenic vs. 4 benign) and the SGM‑Consensus result support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-12.306	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	-0.33	Likely Benign	0.11	Likely Benign	0.21	Likely Benign	0.540	Likely Pathogenic	-6.66	Deleterious	0.988	Probably Damaging	0.734	Possibly Damaging	3.31	Benign	0.01	Affected			0.0686	0.4757		-2	-2	7.7	-29.98
c.1967A>T	E656V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E656V has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (8 of 13) indicate a pathogenic impact, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-15.252	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-0.26	Likely Benign	0.0	-0.10	Likely Benign	-0.18	Likely Benign	-0.77	Ambiguous	0.509	Likely Pathogenic	-6.38	Deleterious	0.784	Possibly Damaging	0.223	Benign	3.46	Benign	0.02	Affected			0.0990	0.7057		-2	-2	7.7	-29.98
c.1997A>T	E666V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools show mixed results: benign calls come from REVEL, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. FoldX alone is uncertain. Overall, the majority of tools and the high‑accuracy consensus favor a pathogenic interpretation, with no conflict from ClinVar status because no classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-10.870	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	0.1	0.08	Likely Benign	0.35	Likely Benign	0.31	Likely Benign	0.476	Likely Benign	-5.95	Deleterious	0.575	Possibly Damaging	0.214	Benign	3.44	Benign	0.03	Affected			0.0818	0.5613		-2	-2	7.7	-29.98
c.2039A>T	E680V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E680V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, premPS, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Rosetta is inconclusive. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, more tools (seven) predict pathogenicity than benign (five), and the high‑accuracy consensus leans toward pathogenic. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.136843	Uncertain	0.636	0.320	0.000											-12.051	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	0.46	Likely Benign	0.3	-1.08	Ambiguous	-0.31	Likely Benign	0.18	Likely Benign	0.454	Likely Benign	-6.21	Deleterious	0.988	Probably Damaging	0.606	Possibly Damaging	3.47	Benign	0.01	Affected			0.1091	0.7518		-2	-2	7.7	-29.98
c.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.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.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.2216A>T	E739V 2D AIThe SynGAP1 missense variant E739V is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM all predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign effect, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.456400	Uncertain	0.313	0.834	0.875					Uncertain		1				-3.136	Likely Benign	0.274	Likely Benign	Likely Benign										0.085	Likely Benign	-1.86	Neutral	0.891	Possibly Damaging	0.575	Possibly Damaging	2.47	Pathogenic	0.00	Affected	4.32	2	0.0953	0.7431		-2	-2	7.7	-29.98
c.224A>T	E75V 2D AIThe SynGAP1 missense variant E75V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, 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 Benign		0.595080	Disordered	0.443881	Uncertain	0.303	0.822	0.500											-3.426	Likely Benign	0.305	Likely Benign	Likely Benign										0.116	Likely Benign	-1.72	Neutral	0.789	Possibly Damaging	0.095	Benign	4.02	Benign	0.00	Affected			0.0878	0.7398		-2	-2	7.7	-29.98
c.2261A>T	E754V 2D AIThe SynGAP1 missense variant E754V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (five benign versus four pathogenic predictions) and the high‑accuracy benign call suggest that the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.750531	Binding	0.357	0.872	0.500											-6.147	Likely Benign	0.601	Likely Pathogenic	Likely Benign										0.157	Likely Benign	-1.86	Neutral	0.966	Probably Damaging	0.773	Possibly Damaging	2.45	Pathogenic	0.28	Tolerated			0.0730	0.7417		-2	-2	7.7	-29.98
c.2375A>T	E792V 2D AIThe SynGAP1 E792V missense change is not listed in ClinVar and has no allele record in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875											-4.643	Likely Benign	0.640	Likely Pathogenic	Likely Benign										0.072	Likely Benign	-3.85	Deleterious	0.000	Benign	0.001	Benign	3.83	Benign	0.00	Affected			0.0987	0.7772		-2	-2	7.7	-29.98
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.272A>T	E91V 2D AIThe SynGAP1 E91V missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. Overall, the evidence is mixed, but the consensus of several independent benign predictors and the SGM‑Consensus lean toward a benign interpretation. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-3.697	Likely Benign	0.934	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-2.16	Neutral	0.947	Possibly Damaging	0.788	Possibly Damaging	3.84	Benign	0.00	Affected			0.0940	0.7457		-2	-2	7.7	-29.98
c.2909A>T	E970V 2D AIThe SynGAP1 missense variant E970V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign interpretation, 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 Benign		0.951925	Disordered	0.953422	Binding	0.342	0.902	0.750											-2.791	Likely Benign	0.208	Likely Benign	Likely Benign										0.245	Likely Benign	-1.08	Neutral	0.002	Benign	0.002	Benign	4.11	Benign	0.08	Tolerated			0.1990	0.7037		-2	-2	7.7	-29.98
c.290A>T	E97V 2D AIThe SynGAP1 missense variant E97V is listed in gnomAD (ID 6‑33425898‑A‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no available result. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta data is missing. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.609018	Binding	0.340	0.867	0.625								6-33425898-A-T	1	6.20e-7	-3.743	Likely Benign	0.514	Ambiguous	Likely Benign										0.124	Likely Benign	-1.17	Neutral	0.947	Possibly Damaging	0.788	Possibly Damaging	4.07	Benign	0.00	Affected	4.32	1	0.1015	0.8155		-2	-2	7.7	-29.98
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.296A>T	E99V 2D AIThe SynGAP1 missense variant E99V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus likewise reports Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for E99V, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.645246	Binding	0.325	0.874	0.500											-3.628	Likely Benign	0.544	Ambiguous	Likely Benign										0.208	Likely Benign	-1.69	Neutral	0.000	Benign	0.000	Benign	4.02	Benign	0.00	Affected			0.1109	0.8175		-2	-2	7.7	-29.98
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.3287A>T	E1096V 2D AIThe SynGAP1 missense variant E1096V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence indicates the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.976475	Binding	0.308	0.858	1.000											-3.588	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.138	Likely Benign	-1.06	Neutral	0.043	Benign	0.017	Benign	2.81	Benign	0.03	Affected			0.1082	0.7596		-2	-2	7.7	-29.98
c.3335A>T	E1112V 2D AIThe SynGAP1 missense variant E1112V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also as benign; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact for E1112V, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.909381	Binding	0.335	0.902	0.875											-3.971	Likely Benign	0.579	Likely Pathogenic	Likely Benign										0.139	Likely Benign	-2.28	Neutral	0.440	Benign	0.140	Benign	2.70	Benign	0.00	Affected			0.1481	0.7567		-2	-2	7.7	-29.98
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.3506A>T	E1169V 2D AIThe SynGAP1 E1169V missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic signal: AlphaMissense‑Optimized is pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive (2 pathogenic vs 2 benign), and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence (seven pathogenic vs three benign predictions) indicates that E1169V is most likely pathogenic. 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.			0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625											-2.482	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.227	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.51	Benign	0.00	Affected			0.0581	0.7028		-2	-2	7.7	-29.98
c.3521A>T	E1174V 2D AIThe SynGAP1 missense variant E1174V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign calls come from PROVEAN, ESM1b, and FATHMM, while pathogenic calls are made by REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Grouping by consensus, the majority of tools (four out of six) predict a benign effect, whereas the remaining four predict pathogenicity. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence leans toward a benign impact for E1174V, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.483068	Structured	0.618958	Binding	0.523	0.734	0.375											-4.814	Likely Benign	0.877	Likely Pathogenic	Ambiguous										0.515	Likely Pathogenic	-2.41	Neutral	0.965	Probably Damaging	0.703	Possibly Damaging	5.41	Benign	0.01	Affected			0.0539	0.6623		-2	-2	7.7	-29.98
c.3527A>T	E1176V 2D AISynGAP1 missense variant E1176V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability approach, has no available result for this variant. Overall, the balance of evidence favors a benign classification, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.572075	Binding	0.525	0.715	0.250											-3.238	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.490	Likely Benign	-2.41	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	5.69	Benign	0.13	Tolerated			0.0452	0.6423		-2	-2	7.7	-29.98
c.3530A>T	E1177V 2D AIThe SynGAP1 E1177V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools predict pathogenicity (5) than benignity (3), and no ClinVar evidence contradicts this assessment. 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.		Coiled-coil	0.541878	Disordered	0.566503	Binding	0.542	0.705	0.250											-3.091	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.481	Likely Benign	-2.90	Deleterious	0.995	Probably Damaging	0.892	Possibly Damaging	5.66	Benign	0.01	Affected			0.0463	0.4520		-2	-2	7.7	-29.98
c.3545A>T	E1182V 2D AIThe SynGAP1 missense variant E1182V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the preponderance of evidence (seven pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.530232	Binding	0.597	0.651	0.375											-4.966	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.124	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.59	Benign	0.00	Affected			0.0447	0.6364		-2	-2	7.7	-29.98
c.3566A>T	E1189V 2D AIThe SynGAP1 E1189V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta stability predictions are not available. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy methods do not overturn this trend. 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.		Coiled-coil	0.562014	Disordered	0.466885	Uncertain	0.704	0.623	0.625											-5.048	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.492	Likely Benign	-3.50	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.26	Benign	0.02	Affected			0.0467	0.4252		-2	-2	7.7	-29.98
c.356A>T	E119V 2D AISynGAP1 missense variant E119V 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, ESM1b, FATHMM, and polyPhen‑2 HumVar, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy methods are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie and is therefore unavailable, and Foldetta results are not provided. Consequently, the evidence does not strongly support either outcome. The variant is most likely inconclusive; it does not clearly favor benign or pathogenic status, and this lack of consensus does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.661946	Binding	0.346	0.881	0.750											-5.696	Likely Benign	0.842	Likely Pathogenic	Ambiguous										0.151	Likely Benign	-2.78	Deleterious	0.596	Possibly Damaging	0.189	Benign	3.79	Benign	0.00	Affected			0.1152	0.7753		-2	-2	7.7	-29.98
c.3590A>T	E1197V 2D AIThe SynGAP1 missense variant E1197V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and therefore unavailable; Foldetta, which would combine FoldX‑MD and Rosetta outputs, has no reported result. Overall, the balance of evidence (five pathogenic versus three benign predictions, with one uncertain) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250											-6.298	Likely Benign	0.923	Likely Pathogenic	Ambiguous										0.472	Likely Benign	-3.28	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.40	Benign	0.03	Affected			0.0440	0.5320		-2	-2	7.7	-29.98
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.3599A>T	E1200V 2D AIThe SynGAP1 E1200V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta data are unavailable. Overall, the majority of standard predictors lean toward pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus leave the variant’s impact uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-4.987	Likely Benign	0.784	Likely Pathogenic	Likely Benign										0.274	Likely Benign	-3.52	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.63	Benign	0.00	Affected			0.0498	0.4648		-2	-2	7.7	-29.98
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.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.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.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.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.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.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