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.334G>T	G112W 2D AIThe SynGAP1 missense variant G112W is not 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 agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from 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 predictions (five pathogenic vs. four benign) lean toward a pathogenic interpretation. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-6.382	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-3.98	Deleterious	0.983	Probably Damaging	0.778	Possibly Damaging	3.90	Benign	0.00	Affected			0.0631	0.4212		-7	-2	-0.5	129.16
c.3379G>T	G1127W 2D AIThe SynGAP1 missense variant G1127W is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443931‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta’s protein‑folding stability result is unavailable. Overall, the balance of evidence, particularly from the high‑accuracy tools, indicates that the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.852422	Binding	0.344	0.915	0.875								6-33443931-G-T	3	2.01e-6	-9.850	Likely Pathogenic	0.418	Ambiguous	Likely Benign										0.394	Likely Benign	-1.36	Neutral	0.983	Probably Damaging	0.665	Possibly Damaging	4.79	Benign	0.03	Affected	4.32	4	0.0782	0.4032		-2	-7	-0.5	129.16
c.337G>T	G113W 2D AIThe SynGAP1 missense variant G113W is 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 (six benign versus four pathogenic predictions) supports a benign classification. 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		0.784345	Disordered	0.639486	Binding	0.350	0.870	0.750											-5.635	Likely Benign	0.620	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-2.44	Neutral	0.983	Probably Damaging	0.717	Possibly Damaging	4.10	Benign	0.01	Affected			0.0700	0.4462		-7	-2	-0.5	129.16
c.3449C>G	A1150G 2D AIThe SynGAP1 A1150G 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, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is 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		0.762850	Disordered	0.795712	Binding	0.371	0.831	0.625											-3.089	Likely Benign	0.253	Likely Benign	Likely Benign										0.158	Likely Benign	-2.37	Neutral	0.983	Probably Damaging	0.818	Possibly Damaging	2.32	Pathogenic	0.09	Tolerated			0.2263	0.4741		1	0	-2.2	-14.03
c.3533A>C	Y1178S 2D AIThe SynGAP1 missense variant Y1178S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect 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, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence from both general and high‑accuracy tools 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	Coiled-coil	0.541878	Disordered	0.568433	Binding	0.554	0.688	0.250											-1.440	Likely Benign	0.771	Likely Pathogenic	Likely Benign										0.329	Likely Benign	-1.53	Neutral	0.983	Probably Damaging	0.769	Possibly Damaging	5.57	Benign	0.33	Tolerated			0.5225	0.1626	Weaken	-3	-2	0.5	-76.10
c.3817C>A	L1273M 2D AIThe SynGAP1 missense variant L1273M is catalogued in gnomAD (ID 6‑33447865‑C‑A) 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) resolves to benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect for the variant. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500								6-33447865-C-A			-5.375	Likely Benign	0.503	Ambiguous	Likely Benign										0.161	Likely Benign	-1.68	Neutral	0.983	Probably Damaging	0.874	Possibly Damaging	2.14	Pathogenic	0.00	Affected	3.77	5	0.0824	0.3932		2	4	-1.9	18.03
c.3889A>T	R1297W 2D AIThe SynGAP1 missense variant R1297W is not 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 results are unavailable. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) indicate a pathogenic impact. This conclusion is consistent with the lack of ClinVar reporting; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.859585	Disordered	0.895222	Binding	0.511	0.817	0.625											-6.039	Likely Benign	0.358	Ambiguous	Likely Benign										0.262	Likely Benign	-4.45	Deleterious	0.983	Probably Damaging	0.868	Possibly Damaging	2.44	Pathogenic	0.01	Affected			0.1260	0.2587		2	-3	3.6	30.03
c.391G>C	G131R 2D AIThe SynGAP1 missense variant G131R 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑to‑2 split and therefore does not contribute evidence. 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 tools predict a pathogenic effect, and the variant is most likely pathogenic based on current predictions, which does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.724779	Binding	0.302	0.891	0.250					Uncertain		1				-6.564	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.82	Deleterious	0.983	Probably Damaging	0.656	Possibly Damaging	3.92	Benign	0.00	Affected	3.61	5	0.1070	0.4667		-2	-3	-4.1	99.14
c.392G>T	G131V 2D AIThe SynGAP1 missense variant G131V is not 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 a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. 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) yields a tie and is therefore unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no result for this variant. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any existing ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.724779	Binding	0.302	0.891	0.250											-6.248	Likely Benign	0.795	Likely Pathogenic	Ambiguous										0.199	Likely Benign	-4.25	Deleterious	0.983	Probably Damaging	0.559	Possibly Damaging	3.92	Benign	0.00	Affected			0.1168	0.4175		-1	-3	4.6	42.08
c.457A>C	T153P 2D AIThe SynGAP1 missense variant T153P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign interpretation. This conclusion does not conflict with ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.502105	Binding	0.297	0.818	0.625											-7.092	In-Between	0.374	Ambiguous	Likely Benign										0.269	Likely Benign	-1.67	Neutral	0.983	Probably Damaging	0.725	Possibly Damaging	4.09	Benign	0.03	Affected			0.2270	0.3660		0	-1	-0.9	-3.99
c.458C>T	T153I 2D AIThe SynGAP1 missense variant T153I is not 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. Those that predict a pathogenic effect comprise polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are limited: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) indicate a 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.			0.501700	Disordered	0.502105	Binding	0.297	0.818	0.625											-8.809	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-2.00	Neutral	0.983	Probably Damaging	0.725	Possibly Damaging	4.08	Benign	0.01	Affected			0.0839	0.4571		0	-1	5.2	12.05
c.526A>T	S176C 2D AIThe SynGAP1 missense variant S176C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both conventional and high‑accuracy tools indicates that the variant is most likely benign, 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.			0.562014	Disordered	0.466016	Uncertain	0.380	0.597	0.375											-9.785	Likely Pathogenic	0.529	Ambiguous	Likely Benign										0.143	Likely Benign	-1.88	Neutral	0.983	Probably Damaging	0.436	Benign	4.02	Benign	0.02	Affected			0.0823	0.5153		0	-1	3.3	16.06
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.545C>G	S182C 2D AIThe SynGAP1 missense variant S182C 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 and 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, 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 preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-12.707	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-3.14	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.63	Benign	0.00	Affected			0.1179	0.5800		0	-1	3.3	16.06
c.554C>G	S185C 2D AIThe SynGAP1 missense variant S185C has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (derived from the same set of predictors) also reports likely pathogenic. Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-10.612	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic										0.266	Likely Benign	-3.96	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.54	Benign	0.00	Affected			0.0989	0.6000		0	-1	3.3	16.06
c.571A>T	S191C 2D AIThe SynGAP1 missense variant S191C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—leans pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of tools and the SGM Consensus predict a pathogenic impact, so the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.009	In-Between	0.709	Likely Pathogenic	Likely Benign										0.288	Likely Benign	-3.39	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.73	Benign	0.00	Affected			0.1064	0.7134		0	-1	3.3	16.06
c.690C>G	C230W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by FATHMM and FoldX, whereas the majority of other in silico predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic impact for C230W, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000											-11.022	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	-0.21	Likely Benign	0.0	-1.87	Ambiguous	-1.04	Ambiguous	0.74	Ambiguous	0.739	Likely Pathogenic	-8.79	Deleterious	0.983	Probably Damaging	0.841	Possibly Damaging	5.84	Benign	0.01	Affected			0.1589	0.3663		-8	-2	-3.4	83.07
c.699T>G	C233W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233W is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome, while Rosetta and premPS are uncertain. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Taken together, the overwhelming majority of evidence indicates that C233W is most likely pathogenic, 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	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000											-17.899	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	14.72	Destabilizing	6.6	1.07	Ambiguous	7.90	Destabilizing	0.54	Ambiguous	0.772	Likely Pathogenic	-9.79	Deleterious	0.983	Probably Damaging	0.715	Possibly Damaging	5.71	Benign	0.00	Affected			0.1727	0.5292		-8	-2	-3.4	83.07
c.907G>T	G303W 2D 3DClick to see structure in 3D Viewer AIClinVar reports no entry for this SynGAP1 G303W variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta’s stability prediction is also unavailable. Overall, the evidence is evenly split between benign and pathogenic predictions, providing no clear bias toward either outcome. This balanced prediction does not contradict ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.450668	Structured	0.271087	Uncertain	0.630	0.254	0.250											-9.041	Likely Pathogenic	0.579	Likely Pathogenic	Likely Benign	1.69	Ambiguous	0.3	1.11	Ambiguous	1.40	Ambiguous	0.28	Likely Benign	0.157	Likely Benign	-1.63	Neutral	0.983	Probably Damaging	0.813	Possibly Damaging	3.93	Benign	0.00	Affected			0.0663	0.4553		-7	-2	-0.5	129.16
c.1649C>T	A550V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A550V variant has no ClinVar entry and is catalogued in gnomAD (ID 6‑33438892‑C‑T). Prediction tools that agree on a benign effect include Foldetta, premPS, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results come from FoldX and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as pathogenic, and Foldetta as benign. Overall, the majority of tools (seven versus four) favor a pathogenic interpretation, and this does not contradict any ClinVar classification because none is available. Thus, based on the current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000								6-33438892-C-T	1	6.20e-7	-10.461	Likely Pathogenic	0.441	Ambiguous	Likely Benign	0.77	Ambiguous	0.2	-0.05	Likely Benign	0.36	Likely Benign	0.48	Likely Benign	0.540	Likely Pathogenic	-2.93	Deleterious	0.984	Probably Damaging	0.494	Possibly Damaging	-1.05	Pathogenic	0.39	Tolerated	3.37	33	0.0874	0.4370		0	0	2.4	28.05
c.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.170T>A	L57H 2D AIThe SynGAP1 missense variant L57H is not reported in ClinVar and has no entry in gnomAD. Prediction tools show a split: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls come from 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 further indicate that AlphaMissense‑Optimized is Uncertain, whereas the SGM‑Consensus remains Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of high‑confidence tools and the consensus score favor a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-6.251	Likely Benign	0.796	Likely Pathogenic	Ambiguous										0.173	Likely Benign	-1.58	Neutral	0.984	Probably Damaging	0.971	Probably Damaging	3.90	Benign	0.00	Affected			0.1045	0.0611		-2	-3	-7.0	23.98
c.1943T>A	F648Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648Y is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID: 6‑33441202‑T‑A). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic classification for F648Y. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000								6-33441202-T-A	4	2.48e-6	-8.632	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.94	Ambiguous	0.84	Ambiguous	1.11	Destabilizing	0.407	Likely Benign	-2.99	Deleterious	0.984	Probably Damaging	0.913	Probably Damaging	3.41	Benign	0.11	Tolerated	3.37	30	0.1307	0.1396		3	7	-4.1	16.00
c.1988T>A	F663Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. Those that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools and the SGM‑Consensus lean toward pathogenicity, while a minority suggest benign impact. Thus, the variant is most likely pathogenic based on the available predictions, 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	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000											-12.749	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous	0.37	Likely Benign	0.1	0.19	Likely Benign	0.28	Likely Benign	1.03	Destabilizing	0.424	Likely Benign	-2.99	Deleterious	0.984	Probably Damaging	0.913	Probably Damaging	3.11	Benign	0.05	Affected			0.1243	0.1584		7	3	-4.1	16.00
c.2201C>G	P734R 2D AIThe SynGAP1 missense variant P734R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.411273	Uncertain	0.368	0.721	0.875											-6.099	Likely Benign	0.288	Likely Benign	Likely Benign										0.115	Likely Benign	-3.00	Deleterious	0.984	Probably Damaging	0.682	Possibly Damaging	2.71	Benign	0.07	Tolerated			0.1664	0.2464		0	-2	-2.9	59.07
c.2249G>T	G750V 2D AIThe SynGAP1 missense variant G750V is not 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 (2 benign vs 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions therefore show AlphaMissense‑Optimized as benign, while the remaining high‑confidence tools (PROVEAN, polyPhen‑2, SIFT, FATHMM) all indicate pathogenicity. Overall, the majority of evidence (five pathogenic vs four benign) points to a pathogenic effect. 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.			0.618285	Disordered	0.646832	Binding	0.348	0.866	0.625											-4.512	Likely Benign	0.134	Likely Benign	Likely Benign										0.145	Likely Benign	-2.54	Deleterious	0.984	Probably Damaging	0.850	Possibly Damaging	2.45	Pathogenic	0.01	Affected			0.1270	0.4212		-1	-3	4.6	42.08
c.2407A>C	K803Q 2D AIThe SynGAP1 missense variant K803Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-2.792	Likely Benign	0.305	Likely Benign	Likely Benign										0.108	Likely Benign	-2.01	Neutral	0.984	Probably Damaging	0.773	Possibly Damaging	2.36	Pathogenic	0.00	Affected			0.4810	0.1398		1	1	0.4	-0.04
c.2440G>C	A814P 2D AIThe SynGAP1 missense variant A814P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly 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 further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) 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 from multiple independent predictors points to a benign effect for A814P, 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	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-5.247	Likely Benign	0.351	Ambiguous	Likely Benign										0.210	Likely Benign	-1.88	Neutral	0.984	Probably Damaging	0.855	Possibly Damaging	2.64	Benign	0.05	Affected			0.1845	0.4941		1	-1	-3.4	26.04
c.2971G>A	G991R 2D AIThe SynGAP1 missense variant G991R is listed in ClinVar (ID 1029090.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443523‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also benign; Foldetta results are 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		0.745909	Disordered	0.911393	Binding	0.286	0.920	0.750					Conflicting		3	6-33443523-G-A	8	4.96e-6	-3.934	Likely Benign	0.411	Ambiguous	Likely Benign										0.102	Likely Benign	-1.20	Neutral	0.984	Probably Damaging	0.772	Possibly Damaging	4.11	Benign	0.01	Affected	4.32	2	0.0956	0.4181		-3	-2	-4.1	99.14
c.2971G>C	G991R 2D AIThe SynGAP1 missense variant G991R is 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 polyPhen‑2 (HumDiv and HumVar) and SIFT all predict 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 further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect for G991R, 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		0.745909	Disordered	0.911393	Binding	0.286	0.920	0.750											-3.934	Likely Benign	0.411	Ambiguous	Likely Benign										0.106	Likely Benign	-1.20	Neutral	0.984	Probably Damaging	0.772	Possibly Damaging	4.11	Benign	0.01	Affected	4.32	2	0.0956	0.4181		-3	-2	-4.1	99.14
c.304T>A	L102M 2D AIThe SynGAP1 missense variant L102M is 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 the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625											-5.033	Likely Benign	0.085	Likely Benign	Likely Benign										0.129	Likely Benign	0.12	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	4.14	Benign	0.00	Affected			0.1091	0.4176		4	2	-1.9	18.03
c.305T>C	L102S 2D AIThe SynGAP1 missense variant L102S 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, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are 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 further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise 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 impact for the L102S variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625											-3.260	Likely Benign	0.105	Likely Benign	Likely Benign										0.174	Likely Benign	0.54	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	4.18	Benign	0.00	Affected			0.2785	0.1752		-3	-2	-4.6	-26.08
c.306G>C	L102F 2D AIThe SynGAP1 missense variant L102F 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 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		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625											-4.712	Likely Benign	0.094	Likely Benign	Likely Benign										0.144	Likely Benign	-0.80	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	4.13	Benign	0.00	Affected			0.0863	0.3205		2	0	-1.0	34.02
c.306G>T	L102F 2D AIThe SynGAP1 missense variant L102F 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 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		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625											-4.712	Likely Benign	0.094	Likely Benign	Likely Benign										0.153	Likely Benign	-0.80	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	4.13	Benign	0.00	Affected			0.0863	0.3205		2	0	-1.0	34.02
c.3266G>T	G1089V 2D AIThe SynGAP1 missense variant G1089V is not 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 results are unavailable. Overall, the majority of evidence points to a pathogenic impact for G1089V. 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.			0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000											-4.809	Likely Benign	0.527	Ambiguous	Likely Benign										0.182	Likely Benign	-2.81	Deleterious	0.984	Probably Damaging	0.722	Possibly Damaging	2.40	Pathogenic	0.00	Affected			0.1326	0.4413		-1	-3	4.6	42.08
c.370G>C	A124P 2D AIThe SynGAP1 missense variant A124P is 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. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for A124P, 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		0.509769	Disordered	0.699139	Binding	0.340	0.883	0.750											-3.030	Likely Benign	0.092	Likely Benign	Likely Benign										0.134	Likely Benign	-1.19	Neutral	0.984	Probably Damaging	0.690	Possibly Damaging	4.05	Benign	0.03	Affected			0.2293	0.6141		1	-1	-3.4	26.04
c.3788T>G	I1263S 2D AIThe SynGAP1 missense variant I1263S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-8.074	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.493	Likely Benign	-4.97	Deleterious	0.984	Probably Damaging	0.825	Possibly Damaging	1.80	Pathogenic	0.00	Affected			0.3242	0.0910		-1	-2	-5.3	-26.08
c.3827A>T	D1276V 2D AIThe SynGAP1 D1276V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.802156	Binding	0.636	0.705	0.625											-0.725	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.331	Likely Benign	-6.66	Deleterious	0.984	Probably Damaging	0.825	Possibly Damaging	1.19	Pathogenic	0.00	Affected			0.0614	0.5207		-2	-3	7.7	-15.96
c.383C>G	P128R 2D AIThe SynGAP1 missense variant P128R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. When predictions are grouped by consensus, the majority of methods (six) predict benign, while three predict pathogenic. 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 a likely benign effect. Foldetta results are unavailable. Overall, the computational evidence favors a benign classification for P128R, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.713069	Binding	0.376	0.878	0.625											-5.048	Likely Benign	0.748	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-1.76	Neutral	0.984	Probably Damaging	0.601	Possibly Damaging	4.19	Benign	0.08	Tolerated			0.1810	0.2401		0	-2	-2.9	59.07
c.3877G>C	D1293H 2D AIThe SynGAP1 missense variant D1293H is not 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 and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) and the SGM Consensus support a pathogenic classification, whereas AlphaMissense‑Optimized suggests benign. The variant is most likely pathogenic based on the collective evidence, and this conclusion does not contradict any ClinVar status because the variant is not yet reported there. 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											-4.422	Likely Benign	0.391	Ambiguous	Likely Benign										0.278	Likely Benign	-4.59	Deleterious	0.984	Probably Damaging	0.888	Possibly Damaging	2.17	Pathogenic	0.00	Affected			0.1609	0.3731		1	-1	0.3	22.05
c.3991A>T	I1331F 2D AIThe SynGAP1 missense variant I1331F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-4.220	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.46	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	3.31	Benign	0.00	Affected			0.0522	0.3225		1	0	-1.7	34.02
c.3992T>A	I1331N 2D AIThe SynGAP1 missense variant I1331N is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451866‑T‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated tools predict a pathogenic impact, and there is no conflict with ClinVar status. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875								6-33451866-T-A			-3.788	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.237	Likely Benign	-4.09	Deleterious	0.984	Probably Damaging	0.979	Probably Damaging	3.29	Benign	0.00	Affected	3.77	5	0.1012	0.0666		-3	-2	-8.0	0.94
c.3992T>G	I1331S 2D AIThe SynGAP1 I1331S variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-3.014	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.230	Likely Benign	-3.40	Deleterious	0.984	Probably Damaging	0.969	Probably Damaging	3.30	Benign	0.00	Affected			0.2929	0.0836		-1	-2	-5.3	-26.08
c.3993T>G	I1331M 2D AIThe SynGAP1 I1331M missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Considering the majority of consensus‑based and individual predictors, the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-4.202	Likely Benign	0.883	Likely Pathogenic	Ambiguous										0.143	Likely Benign	-1.69	Neutral	0.984	Probably Damaging	0.979	Probably Damaging	3.32	Benign	0.00	Affected			0.0698	0.3220		2	1	-2.6	18.03
c.4010T>C	F1337S 2D AIThe SynGAP1 missense variant F1337S is not 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											-2.641	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.327	Likely Benign	-4.65	Deleterious	0.984	Probably Damaging	0.969	Probably Damaging	2.74	Benign	0.00	Affected			0.4478	0.0743		-3	-2	-3.6	-60.10
c.453C>A	D151E 2D AIThe SynGAP1 D151E variant 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, SIFT, ESM1b, and FATHMM. 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, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Benign,” and 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 “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625					Uncertain		1				-5.662	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.02	Neutral	0.984	Probably Damaging	0.967	Probably Damaging	3.99	Benign	0.11	Tolerated	3.61	5	0.1494	0.7919		3	2	0.0	14.03
c.453C>G	D151E 2D AIThe SynGAP1 missense variant D151E is 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 remains 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 D151E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-5.662	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.02	Neutral	0.984	Probably Damaging	0.967	Probably Damaging	3.99	Benign	0.11	Tolerated	3.61	5	0.1494	0.7919		3	2	0.0	14.03
c.664G>A	V222I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V222I 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, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus methods give a benign signal: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, while Foldetta’s stability assessment is uncertain. Overall, the majority of evidence points to a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.116183	Structured	0.402706	Uncertain	0.885	0.310	0.125											-6.347	Likely Benign	0.604	Likely Pathogenic	Likely Benign	0.21	Likely Benign	0.2	1.45	Ambiguous	0.83	Ambiguous	0.09	Likely Benign	0.612	Likely Pathogenic	-0.87	Neutral	0.984	Probably Damaging	0.956	Probably Damaging	5.77	Benign	0.08	Tolerated			0.0637	0.3574		4	3	0.3	14.03
c.664G>C	V222L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V222L 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, Rosetta, FATHMM, and Foldetta, whereas those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (premPS and ESM1b) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—also predicts pathogenic; Foldetta, a protein‑folding stability method, predicts benign. Overall, the majority of evidence (seven pathogenic vs. four benign) points to a pathogenic effect. The variant’s predicted pathogenicity is not contradicted by any ClinVar annotation, as none exists. 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											-7.626	In-Between	0.987	Likely Pathogenic	Likely Pathogenic	0.00	Likely Benign	0.3	0.06	Likely Benign	0.03	Likely Benign	0.60	Ambiguous	0.617	Likely Pathogenic	-2.59	Deleterious	0.984	Probably Damaging	0.956	Probably Damaging	5.49	Benign	0.05	Affected			0.0863	0.4349		2	1	-0.4	14.03
c.664G>T	V222L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V222L 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, Rosetta, FATHMM, and Foldetta, whereas those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (premPS and ESM1b) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—also predicts pathogenic; Foldetta, a protein‑folding stability method, predicts benign. Overall, the majority of evidence (seven pathogenic vs. four benign) points to a pathogenic effect. The variant’s predicted pathogenicity is not contradicted by any ClinVar annotation, as none exists. 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											-7.626	In-Between	0.987	Likely Pathogenic	Likely Pathogenic	0.00	Likely Benign	0.3	0.06	Likely Benign	0.03	Likely Benign	0.60	Ambiguous	0.617	Likely Pathogenic	-2.59	Deleterious	0.984	Probably Damaging	0.956	Probably Damaging	5.49	Benign	0.05	Affected			0.0863	0.4349		2	1	-0.4	14.03
c.665T>C	V222A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V222A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity largely agree: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No predictions are missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.116183	Structured	0.402706	Uncertain	0.885	0.310	0.125											-10.248	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	2.89	Destabilizing	0.3	2.98	Destabilizing	2.94	Destabilizing	2.06	Destabilizing	0.894	Likely Pathogenic	-3.50	Deleterious	0.984	Probably Damaging	0.956	Probably Damaging	5.26	Benign	0.04	Affected			0.2386	0.2081		0	0	-2.4	-28.05
c.682A>C	T228P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T228P 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 FATHMM, Rosetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is inconclusive, but the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-8.559	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.65	Ambiguous	0.6	0.47	Likely Benign	1.06	Ambiguous	0.21	Likely Benign	0.690	Likely Pathogenic	-3.54	Deleterious	0.984	Probably Damaging	0.690	Possibly Damaging	5.64	Benign	0.02	Affected			0.2207	0.6360		0	-1	-0.9	-3.99
c.683C>T	T228I 2D AIThe SynGAP1 missense variant T228I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and 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) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With eight tools favoring pathogenicity versus six favoring benign, and two of the three high‑accuracy methods supporting pathogenicity, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which currently contains no entry for T228I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-8.605	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.02	Likely Benign	0.6	0.21	Likely Benign	0.12	Likely Benign	0.23	Likely Benign	0.692	Likely Pathogenic	-3.99	Deleterious	0.984	Probably Damaging	0.690	Possibly Damaging	5.65	Benign	0.06	Tolerated			0.0951	0.7051		0	-1	5.2	12.05
c.720C>A	D240E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D240E 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, premPS, SIFT, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are 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 as uncertain. Overall, the majority of evaluated predictors (seven pathogenic vs. four benign) lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic based on current computational evidence, 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	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000											-8.619	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.1	0.51	Ambiguous	0.50	Ambiguous	0.28	Likely Benign	0.713	Likely Pathogenic	-3.43	Deleterious	0.984	Probably Damaging	0.967	Probably Damaging	5.84	Benign	0.10	Tolerated			0.1155	0.5066		3	2	0.0	14.03
c.720C>G	D240E 2D 3DClick to see structure in 3D Viewer AISynGAP1 D240E is a missense change in the PH domain. No ClinVar entry exists for this variant, and it is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from SIFT, FoldX, premPS, and FATHMM, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with inconclusive results—AlphaMissense‑Optimized, Rosetta, and Foldetta—are treated as unavailable. High‑accuracy assessments show the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifying the variant as Likely Pathogenic, whereas AlphaMissense‑Optimized and Foldetta provide no definitive verdict. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000											-8.619	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.1	0.51	Ambiguous	0.50	Ambiguous	0.28	Likely Benign	0.713	Likely Pathogenic	-3.43	Deleterious	0.984	Probably Damaging	0.967	Probably Damaging	5.84	Benign	0.10	Tolerated			0.1155	0.5066		3	2	0.0	14.03
c.818A>T	E273V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E273V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and premPS. The majority of tools predict a pathogenic impact: Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, SGM‑Consensus (Likely Pathogenic), and Foldetta. Two tools give inconclusive results: AlphaMissense‑Optimized (Uncertain) and FoldX (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as Pathogenic. Overall, the consensus of pathogenic‑predicting tools outweighs the benign predictions, indicating that E273V 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	C2	0.071867	Structured	0.398918	Uncertain	0.863	0.196	0.125											-11.671	Likely Pathogenic	0.814	Likely Pathogenic	Ambiguous	1.93	Ambiguous	0.3	3.31	Destabilizing	2.62	Destabilizing	0.17	Likely Benign	0.361	Likely Benign	-4.66	Deleterious	0.984	Probably Damaging	0.825	Possibly Damaging	1.70	Pathogenic	0.01	Affected			0.0811	0.3813		-2	-2	7.7	-29.98
c.1141G>A	G381R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G381R is not reported in ClinVar and is present in gnomAD (ID 6‑33438046‑G‑A). Prediction tools that classify it as benign include premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized indicates a benign outcome, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenicity. Overall, the majority of evidence points to a pathogenic impact for G381R, 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	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750								6-33438046-G-A			-8.990	Likely Pathogenic	0.652	Likely Pathogenic	Likely Benign	5.60	Destabilizing	0.9	2.80	Destabilizing	4.20	Destabilizing	0.20	Likely Benign	0.589	Likely Pathogenic	-0.82	Neutral	0.985	Probably Damaging	0.795	Possibly Damaging	1.32	Pathogenic	0.08	Tolerated	4.32	9	0.1339	0.3945		-2	-3	-4.1	99.14
c.1141G>C	G381R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G381R is catalogued in gnomAD (ID 6‑33438046‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from SGM‑Consensus, REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized reports a benign outcome, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenicity. Overall, the majority of evidence indicates a pathogenic impact for G381R, and this conclusion is not contradicted by ClinVar status, which currently lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750								6-33438046-G-C	2	1.25e-6	-8.990	Likely Pathogenic	0.652	Likely Pathogenic	Likely Benign	5.60	Destabilizing	0.9	2.80	Destabilizing	4.20	Destabilizing	0.20	Likely Benign	0.589	Likely Pathogenic	-0.82	Neutral	0.985	Probably Damaging	0.795	Possibly Damaging	1.32	Pathogenic	0.08	Tolerated	4.32	9	0.1339	0.3945		-2	-3	-4.1	99.14
c.1142G>A	G381E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G381E is 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, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools give uncertain results: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. With seven pathogenic versus four benign predictions and two high‑accuracy tools supporting pathogenicity, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750											-9.360	Likely Pathogenic	0.540	Ambiguous	Likely Benign	5.52	Destabilizing	1.1	0.53	Ambiguous	3.03	Destabilizing	0.24	Likely Benign	0.588	Likely Pathogenic	-0.71	Neutral	0.985	Probably Damaging	0.720	Possibly Damaging	1.32	Pathogenic	0.11	Tolerated			0.1554	0.3735		0	-2	-3.1	72.06
c.1157G>T	G386V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G386V is reported in gnomAD (6-33438062‑G‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign classification, 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 Benign	C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750								6-33438062-G-T			-6.405	Likely Benign	0.187	Likely Benign	Likely Benign	4.88	Destabilizing	3.0	5.09	Destabilizing	4.99	Destabilizing	-0.17	Likely Benign	0.458	Likely Benign	-0.64	Neutral	0.985	Probably Damaging	0.720	Possibly Damaging	3.91	Benign	0.01	Affected	4.32	3	0.1685	0.4189		-3	-1	4.6	42.08
c.1523A>T	D508V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D508V missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (a folding‑stability method combining FoldX‑MD and Rosetta outputs) as benign. With seven benign versus six pathogenic calls and two of the three high‑accuracy tools supporting benign, the variant is most likely benign. 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	0.019401	Structured	0.255890	Uncertain	0.890	0.228	0.000											-13.529	Likely Pathogenic	0.691	Likely Pathogenic	Likely Benign	0.07	Likely Benign	0.1	0.66	Ambiguous	0.37	Likely Benign	0.07	Likely Benign	0.381	Likely Benign	-8.37	Deleterious	0.985	Probably Damaging	0.895	Possibly Damaging	3.27	Benign	0.08	Tolerated			0.1050	0.4604		-2	-3	7.7	-15.96
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.1618C>A	Q540K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q540K is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (10 pathogenic vs. 5 benign) indicate a likely pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000											-11.418	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	-0.37	Likely Benign	0.0	-0.03	Likely Benign	-0.20	Likely Benign	0.76	Ambiguous	0.808	Likely Pathogenic	-3.98	Deleterious	0.985	Probably Damaging	0.965	Probably Damaging	-1.31	Pathogenic	0.06	Tolerated			0.1508	0.2472		1	1	-0.4	0.04
c.1819C>G	L607V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607V is listed in ClinVar with an uncertain significance (ClinVar ID 1450275.0) and is present in gnomAD (ID 6‑33440871‑C‑G). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized reports benign, whereas the SGM‑Consensus, derived from the majority of pathogenic predictions, indicates pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore not considered evidence. Overall, the preponderance of computational evidence points to a pathogenic effect for L607V, a conclusion that contrasts with the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000					Uncertain		2	6-33440871-C-G	2	1.24e-6	-11.190	Likely Pathogenic	0.637	Likely Pathogenic	Likely Benign	1.04	Ambiguous	0.2	1.36	Ambiguous	1.20	Ambiguous	0.90	Ambiguous	0.715	Likely Pathogenic	-2.99	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.50	Pathogenic	0.01	Affected	3.37	35	0.1634	0.3577		2	1	0.4	-14.03	216.3	28.1	0.1	0.0	0.9	0.2				X				Potentially Benign	Leu607 is located in a short helical region (res. Ser606-Phe608) within an α-α loop connecting two α helices (res. Glu582-Met603 and res. Glu617-Asn635). In the WT simulations, the iso-butyl side chain of Leu607 does not interact with any other residues, but it could potentially interact directly with Ras due to its location at the GAP domain.In the variant simulations, Val607, which has similar size and physicochemical properties to leucine, does not cause any negative effects on the protein structure. However, due to its location at the GAP-Ras interface, the residue swap could affect the complex formation with the GTPase, but this cannot be investigated using solvent-only simulations.
c.1828C>G	L610V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L610V is reported in gnomAD (ID 6‑33440880‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, while only AlphaMissense‑Optimized predicts a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates benign, whereas the SGM Consensus remains pathogenic and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. With the overwhelming majority of tools predicting pathogenicity and no ClinVar evidence to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-G	3	1.86e-6	-11.304	Likely Pathogenic	0.474	Ambiguous	Likely Benign	2.24	Destabilizing	0.3	0.76	Ambiguous	1.50	Ambiguous	1.21	Destabilizing	0.740	Likely Pathogenic	-2.86	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.46	Pathogenic	0.01	Affected	3.37	35	0.1515	0.3039		1	2	0.4	-14.03
c.1847A>G	D616G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results—FoldX, AlphaMissense‑Default, and Foldetta—are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the predictions are split evenly between benign and pathogenic, with no clear consensus. Thus, the variant is most likely of uncertain significance; it does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-10.310	Likely Pathogenic	0.547	Ambiguous	Likely Benign	1.48	Ambiguous	0.1	2.13	Destabilizing	1.81	Ambiguous	0.49	Likely Benign	0.144	Likely Benign	-5.60	Deleterious	0.985	Probably Damaging	0.800	Possibly Damaging	3.37	Benign	0.06	Tolerated			0.3496	0.4386		1	-1	3.1	-58.04
c.1894A>G	N632D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N632D is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a pathogenic effect, while SGM‑Consensus also indicates a likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM‑Consensus remains likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Because the majority of evidence points to 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	0.042364	Structured	0.041437	Uncertain	0.938	0.254	0.000											-14.117	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	1.84	Ambiguous	0.4	1.50	Ambiguous	1.67	Ambiguous	1.09	Destabilizing	0.827	Likely Pathogenic	-4.31	Deleterious	0.985	Probably Damaging	0.776	Possibly Damaging	-1.53	Pathogenic	0.01	Affected			0.1791	0.3854		2	1	0.0	0.98
c.1910C>A	S637Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of individual predictors (seven versus five) lean toward pathogenicity, and the consensus‑based SGM‑Consensus also supports a likely pathogenic classification. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-12.633	Likely Pathogenic	0.770	Likely Pathogenic	Likely Benign	0.13	Likely Benign	0.1	1.52	Ambiguous	0.83	Ambiguous	0.50	Likely Benign	0.209	Likely Benign	-3.78	Deleterious	0.985	Probably Damaging	0.681	Possibly Damaging	3.35	Benign	0.00	Affected			0.0968	0.4071		-3	-2	-0.5	76.10
c.1910C>G	S637C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, FoldX, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-10.040	Likely Pathogenic	0.138	Likely Benign	Likely Benign	0.25	Likely Benign	0.0	0.54	Ambiguous	0.40	Likely Benign	0.22	Likely Benign	0.169	Likely Benign	-2.83	Deleterious	0.985	Probably Damaging	0.533	Possibly Damaging	3.34	Benign	0.01	Affected			0.1327	0.4439		0	-1	3.3	16.06
c.1910C>T	S637F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S637F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and yields a pathogenic verdict. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points toward a pathogenic impact, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-13.266	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	0.01	Likely Benign	0.1	0.96	Ambiguous	0.49	Likely Benign	0.49	Likely Benign	0.222	Likely Benign	-3.92	Deleterious	0.985	Probably Damaging	0.681	Possibly Damaging	3.35	Benign	0.01	Affected			0.0780	0.4126		-3	-2	3.6	60.10
c.1946T>G	M649R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000											-14.827	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	5.02	Destabilizing	0.1	5.97	Destabilizing	5.50	Destabilizing	2.09	Destabilizing	0.595	Likely Pathogenic	-5.98	Deleterious	0.985	Probably Damaging	0.464	Possibly Damaging	3.33	Benign	0.00	Affected			0.1635	0.1228		0	-1	-6.4	24.99
c.1966G>A	E656K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656K has no ClinVar entry and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” FoldX and Foldetta return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-13.833	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-1.06	Ambiguous	0.0	0.02	Likely Benign	-0.52	Ambiguous	0.16	Likely Benign	0.502	Likely Pathogenic	-3.49	Deleterious	0.985	Probably Damaging	0.553	Possibly Damaging	3.44	Benign	0.03	Affected			0.3001	0.6406		0	1	-0.4	-0.94
c.1967A>C	E656A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments further reveal that AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus also indicates likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No prediction or stability result is missing or inconclusive. Based on the overall evidence, the variant is most likely pathogenic; this assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-14.373	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.0	0.10	Likely Benign	0.11	Likely Benign	-0.13	Likely Benign	0.499	Likely Benign	-5.38	Deleterious	0.985	Probably Damaging	0.755	Possibly Damaging	3.46	Benign	0.03	Affected			0.4244	0.6271		0	-1	5.3	-58.04
c.1968A>C	E656D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656D has no ClinVar entry and is not reported in gnomAD. Prediction tools show mixed results: benign predictions come from REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus confirms Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. No evidence from Foldetta or Rosetta is available to refute pathogenicity. Overall, the majority of high‑confidence tools predict a pathogenic impact, and this is consistent with the absence of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-11.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	0.275	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			0.2052	0.4120		3	2	0.0	-14.03
c.1968A>T	E656D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E656D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign calls (REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic calls (PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus score is “Likely Pathogenic,” while Foldetta and Rosetta outputs are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-11.992	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	0.273	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			0.2052	0.4120		3	2	0.0	-14.03
c.2266C>A	Q756K 2D AIThe SynGAP1 missense variant Q756K is 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. 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 for Q756K, 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		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-6.059	Likely Benign	0.340	Likely Benign	Likely Benign										0.199	Likely Benign	-1.47	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.60	Pathogenic	0.21	Tolerated			0.1816	0.4797		1	1	-0.4	0.04
c.2266C>G	Q756E 2D AIThe SynGAP1 missense variant Q756E is 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, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. 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 Q756E, 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		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-4.149	Likely Benign	0.172	Likely Benign	Likely Benign										0.174	Likely Benign	-1.19	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.58	Pathogenic	0.23	Tolerated			0.1465	0.2853		2	2	0.0	0.98
c.2294G>A	S765N 2D AIThe SynGAP1 missense variant S765N (ClinVar ID 2979632.0) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, PolyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, which is consistent with the ClinVar “Uncertain” classification and does not contradict it. 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					Uncertain		1				-5.098	Likely Benign	0.378	Ambiguous	Likely Benign										0.094	Likely Benign	-0.94	Neutral	0.985	Probably Damaging	0.950	Probably Damaging	4.11	Benign	0.06	Tolerated	3.64	6	0.1141	0.4658		1	1	-2.7	27.03
c.2621A>G	Q874R 2D AIThe SynGAP1 missense variant Q874R is not 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, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. 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 independently predicts a benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points 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.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.834	Likely Benign	0.527	Ambiguous	Likely Benign										0.200	Likely Benign	-2.33	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.69	Benign	0.00	Affected			0.1619	0.2924		1	1	-1.0	28.06
c.2621A>T	Q874L 2D AIThe SynGAP1 missense variant Q874L is not 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 (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four 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 been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-6.084	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.199	Likely Benign	-3.39	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.67	Benign	0.00	Affected			0.0828	0.6595		-2	-2	7.3	-14.97
c.2723A>G	Q908R 2D AIThe SynGAP1 missense variant Q908R is 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 AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates 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 status because none is available. 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											-4.284	Likely Benign	0.485	Ambiguous	Likely Benign										0.170	Likely Benign	-1.02	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.75	Benign	0.10	Tolerated			0.1391	0.1743		1	1	-1.0	28.06
c.2723A>T	Q908L 2D AIThe SynGAP1 missense variant Q908L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. 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 is Likely 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 (none is present). 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											-3.589	Likely Benign	0.420	Ambiguous	Likely Benign										0.193	Likely Benign	-1.40	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.53	Benign	0.05	Affected			0.0706	0.5655		-2	-2	7.3	-14.97
c.2782C>A	Q928K 2D AIThe SynGAP1 missense variant Q928K has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. High‑accuracy evidence therefore consists of an uncertain AlphaMissense‑Optimized score, a Likely Pathogenic SGM‑Consensus, and an unavailable Foldetta prediction. Overall, the majority of tools predict pathogenicity, and there is no ClinVar status to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-4.941	Likely Benign	0.897	Likely Pathogenic	Ambiguous										0.259	Likely Benign	-2.80	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	1.60	Pathogenic	0.00	Affected			0.1728	0.5306		1	1	-0.4	0.04
c.2782C>G	Q928E 2D AIThe SynGAP1 missense variant Q928E is not 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 agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic; 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.			0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-5.168	Likely Benign	0.590	Likely Pathogenic	Likely Benign										0.283	Likely Benign	-2.06	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.58	Pathogenic	0.00	Affected			0.1368	0.3477		2	2	0.0	0.98
c.3062A>G	Q1021R 2D AIThe SynGAP1 missense variant Q1021R is catalogued in gnomAD (ID 6‑33443614‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Benign” (three benign votes versus one pathogenic). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500								6-33443614-A-G	1	6.20e-7	-4.467	Likely Benign	0.770	Likely Pathogenic	Likely Benign										0.174	Likely Benign	-1.80	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.61	Benign	0.03	Affected	3.77	5	0.1257	0.2405		1	1	-1.0	28.06
c.3062A>T	Q1021L 2D AIThe SynGAP1 missense variant Q1021L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. 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.			0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500											-5.780	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-3.36	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.58	Benign	0.01	Affected			0.0688	0.5039		-2	-2	7.3	-14.97
c.3224A>G	Q1075R 2D AIThe SynGAP1 missense variant Q1075R 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, 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 likewise indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as none is assigned to the variant. 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											-5.039	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.142	Likely Benign	-0.37	Neutral	0.985	Probably Damaging	0.973	Probably Damaging	2.72	Benign	0.93	Tolerated			0.1504	0.2650		1	1	-1.0	28.06
c.3224A>T	Q1075L 2D AIThe SynGAP1 missense variant Q1075L 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 confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for Q1075L, and this conclusion is consistent with the absence of a ClinVar assertion. The variant is most likely benign based on predictions, and there is no contradiction with ClinVar status. 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											-3.976	Likely Benign	0.209	Likely Benign	Likely Benign										0.128	Likely Benign	-2.10	Neutral	0.985	Probably Damaging	0.973	Probably Damaging	2.72	Benign	0.15	Tolerated			0.0888	0.6454		-2	-2	7.3	-14.97
c.3317A>G	Q1106R 2D AIThe SynGAP1 missense variant Q1106R is not 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, and FATHMM. AlphaMissense‑Default is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign, one pathogenic, and one uncertain call. 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 (four benign vs. three pathogenic) lean toward a benign interpretation, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.885302	Disordered	0.952043	Binding	0.382	0.870	0.875											-4.211	Likely Benign	0.475	Ambiguous	Likely Benign										0.133	Likely Benign	-2.20	Neutral	0.985	Probably Damaging	0.973	Probably Damaging	1.80	Pathogenic	0.09	Tolerated			0.1412	0.2850		1	1	-1.0	28.06
c.3317A>T	Q1106L 2D AIThe SynGAP1 missense variant Q1106L is not 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). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result 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 is currently unreported in that database. 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											-4.219	Likely Benign	0.171	Likely Benign	Likely Benign										0.169	Likely Benign	-4.46	Deleterious	0.985	Probably Damaging	0.973	Probably Damaging	1.77	Pathogenic	0.05	Affected			0.0833	0.6282		-2	-2	7.3	-14.97
c.3676C>A	Q1226K 2D AIThe SynGAP1 missense variant Q1226K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence therefore points to a likely pathogenic outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta data are missing. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-13.233	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-3.16	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	1.82	Pathogenic	0.00	Affected			0.1334	0.3199		1	1	-0.4	0.04
c.3676C>G	Q1226E 2D AIThe SynGAP1 missense variant Q1226E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the SGM‑Consensus prediction and does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-11.526	Likely Pathogenic	0.625	Likely Pathogenic	Likely Benign										0.178	Likely Benign	-2.13	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.1005	0.2297		2	2	0.0	0.98
c.3685C>A	Q1229K 2D AISynGAP1 missense variant Q1229K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic calls from polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; Foldetta stability analysis is unavailable. Overall, the evidence is split, with an equal number of benign and pathogenic predictions, and the high‑accuracy tools provide one benign and one pathogenic call. Thus, the variant is most likely pathogenic based on the preponderance of pathogenic predictions, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-9.803	Likely Pathogenic	0.471	Ambiguous	Likely Benign										0.159	Likely Benign	-2.36	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.82	Pathogenic	0.22	Tolerated			0.1347	0.2883		1	1	-0.4	0.04
c.3685C>G	Q1229E 2D AIThe SynGAP1 missense change Q1229E lies in a coiled‑coil domain. ClinVar has no entry for this variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. 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.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-7.319	In-Between	0.274	Likely Benign	Likely Benign										0.204	Likely Benign	-1.75	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.80	Pathogenic	0.17	Tolerated			0.1184	0.1336		2	2	0.0	0.98
c.3706C>A	Q1236K 2D AIThe SynGAP1 missense variant Q1236K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign classification, 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.		Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-7.379	In-Between	0.512	Ambiguous	Likely Benign										0.142	Likely Benign	-1.64	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.73	Benign	0.02	Affected			0.1242	0.2503		1	1	-0.4	0.04
c.3706C>G	Q1236E 2D AIThe SynGAP1 missense variant Q1236E 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, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for Q1236E, 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	Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-0.371	Likely Benign	0.146	Likely Benign	Likely Benign										0.263	Likely Benign	0.66	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	3.18	Benign	1.00	Tolerated			0.0985	0.1130		2	2	0.0	0.98
c.3712C>A	Q1238K 2D AIThe SynGAP1 missense variant Q1238K is not 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-8.631	Likely Pathogenic	0.513	Ambiguous	Likely Benign										0.195	Likely Benign	-1.70	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.51	Benign	0.30	Tolerated			0.1345	0.3494		1	1	-0.4	0.04
c.3712C>G	Q1238E 2D AIThe SynGAP1 missense variant Q1238E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically show AlphaMissense‑Optimized predicting benign, while SGM Consensus and Foldetta are unavailable. Overall, the majority of standard predictors (5 pathogenic vs 4 benign) lean toward a pathogenic interpretation, and this assessment does not contradict ClinVar status because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-10.421	Likely Pathogenic	0.312	Likely Benign	Likely Benign										0.201	Likely Benign	-1.90	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.37	Pathogenic	0.02	Affected			0.1078	0.1921		2	2	0.0	0.98
c.3748C>A	Q1250K 2D AIThe SynGAP1 missense variant Q1250K 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, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: 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 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	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-6.804	Likely Benign	0.258	Likely Benign	Likely Benign										0.083	Likely Benign	-0.60	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.81	Benign	0.13	Tolerated			0.1464	0.2484		1	1	-0.4	0.04
c.3748C>G	Q1250E 2D AIThe SynGAP1 missense variant Q1250E 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 (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 prediction is available. Overall, the majority of evidence points to a benign effect for Q1250E, 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	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-3.860	Likely Benign	0.165	Likely Benign	Likely Benign										0.104	Likely Benign	-1.31	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.69	Benign	0.03	Affected			0.1281	0.1130		2	2	0.0	0.98
c.3751C>A	Q1251K 2D AIThe SynGAP1 missense variant Q1251K is catalogued in gnomAD (ID 6‑33446743‑C‑A) but has no ClinVar entry. Functional prediction tools show a split: benign calls from REVEL and FATHMM, whereas the majority—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as Uncertain, SGM‑Consensus remains Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875								6-33446743-C-A	1	6.20e-7	-11.113	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous										0.208	Likely Benign	-2.92	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.53	Benign	0.00	Affected	3.77	5	0.1418	0.2635		1	1	-0.4	0.04
c.3751C>G	Q1251E 2D AIThe SynGAP1 missense variant Q1251E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two uncertain and two benign calls, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.836	In-Between	0.499	Ambiguous	Likely Benign										0.183	Likely Benign	-2.26	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.50	Benign	0.00	Affected			0.1281	0.1266		2	2	0.0	0.98
c.3754C>A	Q1252K 2D AIThe SynGAP1 missense variant Q1252K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the predominance of pathogenic predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-13.590	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous										0.217	Likely Benign	-3.22	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1460	0.2518		1	1	-0.4	0.04
c.3754C>G	Q1252E 2D AIThe SynGAP1 missense variant Q1252E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. three benign) lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-10.181	Likely Pathogenic	0.485	Ambiguous	Likely Benign										0.152	Likely Benign	-2.32	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.01	Pathogenic	0.00	Affected			0.1130	0.1266		2	2	0.0	0.98
c.3772C>A	Q1258K 2D AIThe SynGAP1 missense variant Q1258K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify it as pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by seven distinct algorithms. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as likely pathogenic, and Foldetta data are not available. Taken together, the preponderance of evidence from multiple pathogenic predictors and the SGM‑Consensus suggests that the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.927	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.227	Likely Benign	-3.19	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1151	0.2761		1	1	-0.4	0.04
c.3772C>G	Q1258E 2D AIThe SynGAP1 missense variant Q1258E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-9.894	Likely Pathogenic	0.666	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-2.39	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.01	Pathogenic	0.00	Affected			0.0958	0.1897		2	2	0.0	0.98
c.4000A>C	N1334H 2D AIThe SynGAP1 missense variant N1334H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of reliable tools and the high‑accuracy consensus predict a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-4.954	Likely Benign	0.496	Ambiguous	Likely Benign										0.164	Likely Benign	-2.99	Deleterious	0.985	Probably Damaging	0.927	Probably Damaging	3.50	Benign	0.00	Affected			0.1963	0.6246		2	1	0.3	23.04
c.4000A>T	N1334Y 2D AIThe SynGAP1 missense variant N1334Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive; Foldetta results are unavailable. Overall, the majority of conventional tools predict a pathogenic impact, but the single high‑accuracy benign prediction and the inconclusive consensus suggest uncertainty. Consequently, the variant is most likely pathogenic based on the prevailing evidence, and this assessment does not contradict any ClinVar annotation because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-5.916	Likely Benign	0.770	Likely Pathogenic	Likely Benign										0.249	Likely Benign	-4.62	Deleterious	0.985	Probably Damaging	0.852	Possibly Damaging	3.49	Benign	0.00	Affected			0.0716	0.5447		-2	-2	2.2	49.07
c.4001A>T	N1334I 2D AIThe SynGAP1 missense variant N1334I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the balance of evidence (seven pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-5.880	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-5.06	Deleterious	0.985	Probably Damaging	0.721	Possibly Damaging	3.50	Benign	0.00	Affected			0.0861	0.5491		-2	-3	8.0	-0.94
c.562A>C	S188R 2D AIThe SynGAP1 missense variant S188R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the S188R 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		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-11.567	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.269	Likely Benign	-3.82	Deleterious	0.985	Probably Damaging	0.767	Possibly Damaging	3.92	Benign	0.00	Affected			0.0916	0.4236		0	-1	-3.7	69.11
c.564T>A	S188R 2D AIThe SynGAP1 missense variant S188R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the S188R 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		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-11.567	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-3.82	Deleterious	0.985	Probably Damaging	0.767	Possibly Damaging	3.92	Benign	0.00	Affected			0.0916	0.4236		0	-1	-3.7	69.11
c.564T>G	S188R 2D AIThe SynGAP1 missense variant S188R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-11.567	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.263	Likely Benign	-3.82	Deleterious	0.985	Probably Damaging	0.767	Possibly Damaging	3.92	Benign	0.00	Affected			0.0916	0.4236		0	-1	-3.7	69.11
c.620A>T	K207M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K207M 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, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact; premPS is uncertain. High‑accuracy methods give mixed results: 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) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.596	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	-0.22	Likely Benign	0.0	-0.47	Likely Benign	-0.35	Likely Benign	0.59	Ambiguous	0.336	Likely Benign	-4.67	Deleterious	0.985	Probably Damaging	0.832	Possibly Damaging	3.94	Benign	0.03	Affected			0.0982	0.4705		0	-1	5.8	3.02
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.722A>T	K241I 2D 3DClick to see structure in 3D Viewer AISynGAP1 K241I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, premPS, and FATHMM. Those that predict a damaging effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). FoldX and Foldetta return uncertain results. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized reports pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, while Foldetta remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-14.370	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.31	Ambiguous	0.5	0.28	Likely Benign	0.80	Ambiguous	0.41	Likely Benign	0.852	Likely Pathogenic	-6.96	Deleterious	0.985	Probably Damaging	0.704	Possibly Damaging	5.71	Benign	0.01	Affected			0.1176	0.3868		-2	-3	8.4	-15.01
c.727A>T	I243F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I243F 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, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give inconclusive results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus unavailable; Foldetta is uncertain. Overall, the majority of available predictions (7 pathogenic vs. 3 benign) indicate a likely pathogenic impact. This assessment 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	0.363090	Structured	0.344471	Uncertain	0.842	0.347	0.000											-12.559	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	2.92	Destabilizing	2.5	0.53	Ambiguous	1.73	Ambiguous	0.42	Likely Benign	0.793	Likely Pathogenic	-2.21	Neutral	0.985	Probably Damaging	0.724	Possibly Damaging	5.53	Benign	0.02	Affected			0.0409	0.2205		1	0	-1.7	34.02
c.729T>G	I243M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I243M has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign”; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts a benign effect. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates that the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.363090	Structured	0.344471	Uncertain	0.842	0.347	0.000											-4.305	Likely Benign	0.175	Likely Benign	Likely Benign	0.09	Likely Benign	0.1	0.16	Likely Benign	0.13	Likely Benign	-0.01	Likely Benign	0.474	Likely Benign	0.58	Neutral	0.985	Probably Damaging	0.798	Possibly Damaging	5.61	Benign	0.94	Tolerated			0.0553	0.2200		2	1	-2.6	18.03
c.1154C>G	S385W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S385W is listed in ClinVar as Benign (ClinVar ID 218691.0) and is present in gnomAD (ID 6‑33438059‑C‑G). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, 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 ESM1b. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM Consensus as Benign, and Foldetta as Uncertain. Taken together, the majority of evidence points to a benign impact, which aligns with the ClinVar classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.425480	Uncertain	0.341	0.925	0.750					Benign		1	6-33438059-C-G			-9.353	Likely Pathogenic	0.362	Ambiguous	Likely Benign	0.53	Ambiguous	0.2	0.69	Ambiguous	0.61	Ambiguous	0.00	Likely Benign	0.373	Likely Benign	-0.84	Neutral	0.986	Probably Damaging	0.968	Probably Damaging	4.63	Benign	0.00	Affected	4.32	3	0.1272	0.6670		-2	-3	-0.1	99.14	260.4	-71.2	0.5	1.3	0.7	0.4								Uncertain	Ser385 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364, res. Ala399-Ile411). Because the Ω loop is assumed to directly interact with the membrane, it moves arbitrarily throughout the WT solvent simulations. The Ω loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play major roles in protein functions that require flexibility, and thus hydrophobic residues like tryptophan are rarely tolerated. Although no major negative structural effects are observed in the variant simulations, Trp385 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effects on Gly-rich Ω loop dynamics can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn.	10.1016/j.ajhg.2020.11.011
c.1308G>C	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1308G>T	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1338G>C	E446D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a damaging effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Taken together, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-5.668	Likely Benign	0.562	Ambiguous	Likely Benign	1.65	Ambiguous	0.7	0.80	Ambiguous	1.23	Ambiguous	0.68	Ambiguous	0.171	Likely Benign	-2.40	Neutral	0.986	Probably Damaging	0.960	Probably Damaging	3.30	Benign	0.18	Tolerated			0.1657	0.4275		3	2	0.0	-14.03
c.1338G>T	E446D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E446D lies in the GAP domain. ClinVar has no entry for this variant and it is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools report a pathogenic signal: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The remaining predictors (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Taken together, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this is consistent with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-5.668	Likely Benign	0.562	Ambiguous	Likely Benign	1.65	Ambiguous	0.7	0.80	Ambiguous	1.23	Ambiguous	0.68	Ambiguous	0.171	Likely Benign	-2.40	Neutral	0.986	Probably Damaging	0.960	Probably Damaging	3.30	Benign	0.18	Tolerated			0.1657	0.4275		3	2	0.0	-14.03
c.155C>G	S52W 2D AIThe SynGAP1 missense variant S52W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and no high‑accuracy consensus or folding‑stability evidence contradicts this trend. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not conflict with the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.291804	Structured	0.457753	Uncertain	0.499	0.677	0.000											-8.649	Likely Pathogenic	0.909	Likely Pathogenic	Ambiguous										0.155	Likely Benign	-1.85	Neutral	0.986	Probably Damaging	0.968	Probably Damaging	4.05	Benign	0.00	Affected			0.0580	0.6254		-2	-3	-0.1	99.14
c.1563G>C	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E521D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a Benign effect. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1563G>T	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521D missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome. The high‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1566A>C	E522D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522D missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and ESM1b, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a benign effect. Overall, the balance of evidence points to a likely pathogenic impact for E522D, 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	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-5.385	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.1	-0.02	Likely Benign	0.01	Likely Benign	0.32	Likely Benign	0.494	Likely Benign	-2.65	Deleterious	0.986	Probably Damaging	0.989	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0.1499	0.2765		3	2	0.0	-14.03
c.1566A>T	E522D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E522D missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and ESM1b, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a benign effect. Overall, the balance of evidence points to a likely pathogenic impact for E522D, 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	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-5.385	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.04	Likely Benign	0.1	-0.02	Likely Benign	0.01	Likely Benign	0.32	Likely Benign	0.494	Likely Benign	-2.65	Deleterious	0.986	Probably Damaging	0.989	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0.1499	0.2765		3	2	0.0	-14.03
c.1746G>C	E582D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E582D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: a benign group comprising REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, and a pathogenic group containing polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Remaining tools (FoldX, Rosetta, ESM1b, AlphaMissense‑Default) yield uncertain results and are treated as unavailable. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans toward benign, and Foldetta indicates no significant destabilization. Consequently, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-7.974	In-Between	0.520	Ambiguous	Likely Benign	0.57	Ambiguous	0.2	0.95	Ambiguous	0.76	Ambiguous	0.40	Likely Benign	0.093	Likely Benign	-1.63	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.22	Benign	0.27	Tolerated			0.1481	0.2236		3	2	0.0	-14.03
c.1746G>T	E582D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E582D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: a benign group comprising REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, and a pathogenic group consisting of polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Remaining tools (FoldX, Rosetta, ESM1b, AlphaMissense‑Default) yield uncertain results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because two of the four inputs are uncertain; Foldetta, which integrates FoldX‑MD and Rosetta outputs, also reports an uncertain stability change. Consequently, the preponderance of evidence points to a benign effect. This conclusion aligns with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-7.974	In-Between	0.520	Ambiguous	Likely Benign	0.57	Ambiguous	0.2	0.95	Ambiguous	0.76	Ambiguous	0.40	Likely Benign	0.093	Likely Benign	-1.63	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.22	Benign	0.27	Tolerated			0.1481	0.2236		3	2	0.0	-14.03
c.1949A>C	N650T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N650T is not 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, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.361944	Uncertain	0.961	0.357	0.000											-13.626	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.73	Ambiguous	0.52	Ambiguous	0.69	Ambiguous	0.471	Likely Benign	-5.98	Deleterious	0.986	Probably Damaging	0.710	Possibly Damaging	3.04	Benign	0.01	Affected			0.1700	0.4843		0	0	2.8	-13.00
c.1952A>C	E651A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E651A missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicting it as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign impact. Overall, the balance of evidence leans toward a benign classification, and this conclusion does not contradict the absence of a ClinVar record. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-8.694	Likely Pathogenic	0.610	Likely Pathogenic	Likely Benign	0.38	Likely Benign	0.1	0.52	Ambiguous	0.45	Likely Benign	0.23	Likely Benign	0.396	Likely Benign	-4.54	Deleterious	0.986	Probably Damaging	0.875	Possibly Damaging	3.33	Benign	0.13	Tolerated			0.3926	0.5551		0	-1	5.3	-58.04
c.1961A>C	E654A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E654A has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Benign. Overall, the balance of evidence favors pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-10.797	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.1	0.20	Likely Benign	0.35	Likely Benign	0.25	Likely Benign	0.512	Likely Pathogenic	-5.70	Deleterious	0.986	Probably Damaging	0.875	Possibly Damaging	3.34	Benign	0.02	Affected			0.3367	0.3971		0	-1	5.3	-58.04
c.2210A>G	Q737R 2D AIThe SynGAP1 missense variant Q737R 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, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: 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 Q737R, 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		0.889439	Disordered	0.425743	Uncertain	0.323	0.803	0.875											-4.524	Likely Benign	0.159	Likely Benign	Likely Benign										0.077	Likely Benign	-1.02	Neutral	0.986	Probably Damaging	0.793	Possibly Damaging	2.74	Benign	0.06	Tolerated			0.1688	0.1852		1	1	-1.0	28.06
c.2516A>C	K839T 2D AIThe SynGAP1 missense variant K839T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign calls are limited to REVEL, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the consensus of the majority of in silico tools indicates that K839T is most likely pathogenic, and this conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-11.946	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.235	Likely Benign	-3.79	Deleterious	0.986	Probably Damaging	0.922	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.2119	0.4164		0	-1	3.2	-27.07
c.2531T>C	L844P 2D AIThe SynGAP1 missense variant L844P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessment further supports a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both conventional and high‑accuracy tools indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375											-7.425	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-3.18	Deleterious	0.986	Probably Damaging	0.876	Possibly Damaging	2.58	Benign	0.01	Affected			0.3528	0.1458		-3	-3	-5.4	-16.04
c.2602G>A	D868N 2D AIThe SynGAP1 D868N missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (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 likewise indicates 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, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-3.052	Likely Benign	0.419	Ambiguous	Likely Benign										0.161	Likely Benign	-2.01	Neutral	0.986	Probably Damaging	0.922	Probably Damaging	2.55	Benign	0.21	Tolerated			0.1977	0.7152		2	1	0.0	-0.98
c.2603A>G	D868G 2D AIThe SynGAP1 missense variant D868G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM Consensus) – derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN – is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-2.218	Likely Benign	0.552	Ambiguous	Likely Benign										0.113	Likely Benign	-2.71	Deleterious	0.986	Probably Damaging	0.860	Possibly Damaging	2.51	Benign	0.21	Tolerated			0.4658	0.6414		1	-1	3.1	-58.04
c.2630T>A	L877Q 2D AIThe SynGAP1 missense variant L877Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. 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 is Likely Benign, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the collective evidence, 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		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-5.919	Likely Benign	0.460	Ambiguous	Likely Benign										0.152	Likely Benign	-1.58	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.57	Benign	0.03	Affected			0.1208	0.0919		-2	-2	-7.3	14.97
c.2630T>C	L877P 2D AIThe SynGAP1 missense variant L877P 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 interpretation: 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 for this variant. Overall, the majority of computational evidence points to a benign effect, 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		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-4.960	Likely Benign	0.312	Likely Benign	Likely Benign										0.154	Likely Benign	-1.57	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.59	Benign	0.03	Affected			0.3899	0.1543		-3	-3	-5.4	-16.04
c.2630T>G	L877R 2D AIThe SynGAP1 missense variant L877R 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 (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 this variant, and this conclusion does not contradict the 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 Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-6.678	Likely Benign	0.673	Likely Pathogenic	Likely Benign										0.148	Likely Benign	-1.82	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.57	Benign	0.02	Affected			0.1218	0.0761		-3	-2	-8.3	43.03
c.2635G>C	A879P 2D AIThe SynGAP1 missense variant A879P is 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 impact. 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 A879P 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		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250											-4.317	Likely Benign	0.114	Likely Benign	Likely Benign										0.151	Likely Benign	-1.16	Neutral	0.986	Probably Damaging	0.825	Possibly Damaging	2.61	Benign	0.23	Tolerated			0.1713	0.5004		1	-1	-3.4	26.04
c.2705C>A	A902D 2D AIThe SynGAP1 missense variant A902D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, 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 Benign		0.675549	Disordered	0.517703	Binding	0.319	0.919	0.375											-5.273	Likely Benign	0.823	Likely Pathogenic	Ambiguous										0.101	Likely Benign	-1.21	Neutral	0.986	Probably Damaging	0.787	Possibly Damaging	2.59	Benign	0.00	Affected			0.1653	0.1609		0	-2	-5.3	44.01
c.2966C>A	S989Y 2D AIThe SynGAP1 missense variant S989Y is not 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, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy predictions therefore indicate a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus is benign, and Foldetta data are unavailable. Consequently, the variant is most likely benign based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.795062	Disordered	0.908835	Binding	0.296	0.911	0.750											-4.774	Likely Benign	0.471	Ambiguous	Likely Benign										0.103	Likely Benign	-3.32	Deleterious	0.986	Probably Damaging	0.876	Possibly Damaging	2.60	Benign	0.00	Affected			0.0611	0.4815		-3	-2	-0.5	76.10
c.2966C>T	S989F 2D AIThe SynGAP1 missense variant S989F is not 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, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of reliable predictors and the consensus high‑accuracy tools indicate a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.795062	Disordered	0.908835	Binding	0.296	0.911	0.750											-4.115	Likely Benign	0.435	Ambiguous	Likely Benign										0.109	Likely Benign	-3.35	Deleterious	0.986	Probably Damaging	0.876	Possibly Damaging	2.60	Benign	0.00	Affected			0.0598	0.5103		-3	-2	3.6	60.10
c.3050T>C	F1017S 2D AIThe SynGAP1 missense variant F1017S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625											-1.804	Likely Benign	0.782	Likely Pathogenic	Likely Benign										0.114	Likely Benign	-3.16	Deleterious	0.986	Probably Damaging	0.848	Possibly Damaging	2.46	Pathogenic	0.00	Affected			0.4491	0.0000		-3	-2	-3.6	-60.10
c.3065T>G	L1022R 2D AIThe SynGAP1 missense variant L1022R is not reported in ClinVar and has no entries 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 this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L1022R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500											-2.875	Likely Benign	0.659	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-1.96	Neutral	0.986	Probably Damaging	0.894	Possibly Damaging	2.51	Benign	0.01	Affected			0.1279	0.1387		-3	-2	-8.3	43.03
c.3082C>A	L1028M 2D AIThe SynGAP1 missense variant L1028M is 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, 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 the variant, 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		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500											-4.591	Likely Benign	0.229	Likely Benign	Likely Benign										0.082	Likely Benign	-0.07	Neutral	0.986	Probably Damaging	0.825	Possibly Damaging	2.70	Benign	0.18	Tolerated			0.0776	0.3124		4	2	-1.9	18.03
c.3083T>A	L1028Q 2D AIThe SynGAP1 missense variant L1028Q is 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 AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 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 because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500											-2.718	Likely Benign	0.612	Likely Pathogenic	Likely Benign										0.179	Likely Benign	-0.19	Neutral	0.986	Probably Damaging	0.825	Possibly Damaging	2.80	Benign	0.38	Tolerated			0.1110	0.1403		-2	-2	-7.3	14.97
c.3119G>A	G1040D 2D AIThe SynGAP1 missense variant G1040D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The high‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that G1040D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-4.154	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.761	Likely Pathogenic	-2.82	Deleterious	0.986	Probably Damaging	0.787	Possibly Damaging	-0.74	Pathogenic	0.00	Affected			0.1677	0.2042		1	-1	-3.1	58.04
c.3122C>G	P1041R 2D AIThe SynGAP1 missense variant P1041R 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, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The AlphaMissense‑Default result is uncertain, and no Foldetta stability data are available, so these are treated as unavailable. Overall, six tools support a benign classification while three support pathogenicity, and the high‑accuracy AlphaMissense‑Optimized and SGM Consensus both predict benign. Therefore, the variant is most likely benign based on the current predictions, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.962114	Disordered	0.967463	Binding	0.345	0.833	0.625											-4.808	Likely Benign	0.545	Ambiguous	Likely Benign										0.443	Likely Benign	-3.33	Deleterious	0.986	Probably Damaging	0.787	Possibly Damaging	5.46	Benign	0.07	Tolerated			0.1401	0.4292		0	-2	-2.9	59.07
c.3179G>T	G1060V 2D AIThe SynGAP1 missense variant G1060V is listed in ClinVar as benign (ClinVar ID 1345112.0) and is observed in gnomAD (6‑33443731‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect. 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 outcome. No Foldetta stability assessment is available for this variant. Overall, the majority of evidence points to a benign impact, aligning with the ClinVar designation and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.979242	Disordered	0.913048	Binding	0.407	0.928	0.875					Benign		1	6-33443731-G-T	1	6.22e-7	-6.966	Likely Benign	0.103	Likely Benign	Likely Benign										0.369	Likely Benign	-0.73	Neutral	0.986	Probably Damaging	0.728	Possibly Damaging	2.63	Benign	0.33	Tolerated	4.32	2	0.1453	0.3494		-1	-3	4.6	42.08
c.3274T>A	L1092M 2D AIThe SynGAP1 missense variant L1092M is not reported in ClinVar and has no entries in gnomAD, indicating it has not been catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the substitution as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy predictions from AlphaMissense‑Optimized and the SGM‑Consensus both support a benign outcome, whereas the absence of a Foldetta result precludes a stability‑based conclusion. Overall, the majority of evidence points to a benign effect for the variant, 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		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000											-5.348	Likely Benign	0.383	Ambiguous	Likely Benign										0.083	Likely Benign	-0.15	Neutral	0.986	Probably Damaging	0.875	Possibly Damaging	2.66	Benign	0.21	Tolerated			0.0919	0.4479		4	2	-1.9	18.03
c.3275T>C	L1092S 2D AIThe SynGAP1 missense variant L1092S is 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 SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. 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 for this variant. 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		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000											-3.649	Likely Benign	0.900	Likely Pathogenic	Ambiguous										0.121	Likely Benign	-0.42	Neutral	0.986	Probably Damaging	0.823	Possibly Damaging	2.68	Benign	0.25	Tolerated			0.3086	0.1119		-3	-2	-4.6	-26.08
c.3276G>C	L1092F 2D AIThe SynGAP1 missense variant L1092F is reported in gnomAD (6‑33443828‑G‑C) but has no ClinVar entry. 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, 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 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 is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000								6-33443828-G-C	1	6.40e-7	-5.010	Likely Benign	0.623	Likely Pathogenic	Likely Benign										0.067	Likely Benign	-1.40	Neutral	0.986	Probably Damaging	0.823	Possibly Damaging	2.63	Benign	0.18	Tolerated	3.77	5	0.0772	0.4060		0	2	-1.0	34.02
c.3276G>T	L1092F 2D AIThe SynGAP1 missense variant L1092F is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools show a split: benign calls from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also leans benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation and gnomAD absence. Therefore, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000											-5.010	Likely Benign	0.623	Likely Pathogenic	Likely Benign										0.067	Likely Benign	-1.40	Neutral	0.986	Probably Damaging	0.823	Possibly Damaging	2.63	Benign	0.18	Tolerated	3.77	5	0.0772	0.4060		0	2	-1.0	34.02
c.3311C>A	P1104Q 2D AIThe SynGAP1 missense variant P1104Q is reported in gnomAD (ID 6‑33443863‑C‑A) 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. 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 the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. 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 assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.936162	Disordered	0.954801	Binding	0.440	0.863	0.875								6-33443863-C-A			-3.161	Likely Benign	0.104	Likely Benign	Likely Benign										0.114	Likely Benign	-0.64	Neutral	0.986	Probably Damaging	0.825	Possibly Damaging	2.68	Benign	0.06	Tolerated	3.77	5	0.1498	0.5063		-1	0	-1.9	31.01
c.3311C>G	P1104R 2D AIThe SynGAP1 missense variant P1104R 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. 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 further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign impact, 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		0.936162	Disordered	0.954801	Binding	0.440	0.863	0.875											-3.864	Likely Benign	0.328	Likely Benign	Likely Benign										0.099	Likely Benign	-0.64	Neutral	0.986	Probably Damaging	0.761	Possibly Damaging	2.68	Benign	0.06	Tolerated			0.1387	0.3703		0	-2	-2.9	59.07
c.3337G>C	G1113R 2D AIThe SynGAP1 missense variant G1113R is 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 AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 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 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		0.905695	Disordered	0.900456	Binding	0.327	0.910	0.875											-4.765	Likely Benign	0.618	Likely Pathogenic	Likely Benign										0.063	Likely Benign	-1.54	Neutral	0.986	Probably Damaging	0.848	Possibly Damaging	2.65	Benign	0.64	Tolerated			0.0939	0.4426		-3	-2	-4.1	99.14
c.3428C>A	T1143K 2D AIThe SynGAP1 missense variant T1143K is 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 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 outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for T1143K, 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		0.919029	Disordered	0.722918	Binding	0.275	0.837	1.000											-3.498	Likely Benign	0.811	Likely Pathogenic	Ambiguous										0.163	Likely Benign	-2.03	Neutral	0.986	Probably Damaging	0.895	Possibly Damaging	2.78	Benign	0.14	Tolerated			0.1266	0.2936		0	-1	-3.2	27.07
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.3547T>G	Y1183D 2D AISynGAP1 missense variant Y1183D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools show mixed results: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, a majority‑vote model of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts the variant as likely benign. High‑accuracy assessments further indicate AlphaMissense‑Optimized as pathogenic, whereas Foldetta (FoldX‑MD/Rosetta stability analysis) is not available for this residue. Overall, the balance of evidence leans toward a benign effect, and this assessment does not conflict with ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500											-2.718	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.097	Likely Benign	-1.10	Neutral	0.986	Probably Damaging	0.787	Possibly Damaging	2.83	Benign	0.61	Tolerated			0.4602	0.0243		-4	-3	-2.2	-48.09
c.1082A>G	Q361R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, SIFT, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Rosetta; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus itself is benign; and Foldetta, which integrates FoldX‑MD (Uncertain) and Rosetta (Benign), yields a benign prediction. Overall, the consensus of available computational evidence 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	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-6.898	Likely Benign	0.289	Likely Benign	Likely Benign	-0.88	Ambiguous	0.0	-0.07	Likely Benign	-0.48	Likely Benign	-0.20	Likely Benign	0.296	Likely Benign	-0.56	Neutral	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.41	Tolerated			0.1321	0.2955		1	1	-1.0	28.06
c.1082A>T	Q361L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8 benign vs 5 pathogenic) favor a benign effect, and this consensus does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-10.678	Likely Pathogenic	0.238	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.46	Likely Benign	0.29	Likely Benign	0.21	Likely Benign	0.406	Likely Benign	-3.95	Deleterious	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.06	Tolerated			0.0720	0.5213		-2	-2	7.3	-14.97
c.1168G>T	G390W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G390W is 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‑Optimized, premPS, and PROVEAN, whereas the remaining tools—REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts benign, but the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict, and Foldetta also indicates pathogenic. With the majority of evidence pointing to a deleterious effect, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.626927	Disordered	0.413274	Uncertain	0.304	0.763	0.875											-9.405	Likely Pathogenic	0.487	Ambiguous	Likely Benign	3.69	Destabilizing	1.9	5.31	Destabilizing	4.50	Destabilizing	0.14	Likely Benign	0.639	Likely Pathogenic	-1.11	Neutral	0.987	Probably Damaging	0.744	Possibly Damaging	1.31	Pathogenic	0.00	Affected			0.0917	0.4368		-7	-2	-0.5	129.16
c.1191C>G	C397W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign calls come from premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus, whereas pathogenic calls are made by REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, but Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts pathogenic. Overall, the majority of tools lean toward a benign effect, and this is consistent with the lack of ClinVar evidence. Therefore, the variant is most likely benign, and there is no contradiction with ClinVar status. 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											-6.857	Likely Benign	0.614	Likely Pathogenic	Likely Benign	2.40	Destabilizing	2.3	4.46	Destabilizing	3.43	Destabilizing	0.19	Likely Benign	0.545	Likely Pathogenic	-1.87	Neutral	0.987	Probably Damaging	0.814	Possibly Damaging	4.64	Benign	0.02	Affected			0.1637	0.5092		-8	-2	-3.4	83.07
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.127G>T	G43C 2D AIThe SynGAP1 missense variant G43C 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 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		0.308712	Structured	0.431462	Uncertain	0.396	0.762	0.375											-4.599	Likely Benign	0.109	Likely Benign	Likely Benign										0.077	Likely Benign	-0.90	Neutral	0.987	Probably Damaging	0.750	Possibly Damaging	4.18	Benign	0.00	Affected			0.1445	0.3438		-3	-3	2.9	46.09
c.1333G>C	E445Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E445Q is reported in gnomAD (ID 6‑33438238‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b). Two tools remain inconclusive (premPS, AlphaMissense‑Optimized). High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign impact. Overall, the balance of evidence tilts toward pathogenicity, with the high‑accuracy consensus supporting this view, and there is no conflict with ClinVar status because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000								6-33438238-G-C	1	6.19e-7	-12.430	Likely Pathogenic	0.790	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	0.20	Likely Benign	0.09	Likely Benign	0.70	Ambiguous	0.240	Likely Benign	-2.86	Deleterious	0.987	Probably Damaging	0.946	Probably Damaging	3.40	Benign	0.12	Tolerated	3.38	31	0.0787	0.5018		2	2	0.0	-0.98
c.1367A>T	Q456L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Tools with uncertain or inconclusive results are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, with no evidence of contradiction with the ClinVar status. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-10.272	Likely Pathogenic	0.492	Ambiguous	Likely Benign	-0.88	Ambiguous	0.1	-0.30	Likely Benign	-0.59	Ambiguous	0.28	Likely Benign	0.347	Likely Benign	-6.65	Deleterious	0.987	Probably Damaging	0.914	Probably Damaging	3.49	Benign	0.36	Tolerated			0.0554	0.4317		-2	-2	7.3	-14.97
c.1399G>A	D467N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D467N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of the four high‑accuracy predictors) all predict a deleterious effect. Benign predictions come from FoldX, premPS, and SIFT. Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy methods specifically give an uncertain result for AlphaMissense‑Optimized, a pathogenic verdict for the SGM‑Consensus, and an uncertain outcome for Foldetta. Overall, the balance of evidence favors a pathogenic impact for D467N, 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	GAP	0.268042	Structured	0.329932	Uncertain	0.940	0.246	0.000											-11.881	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.1	1.63	Ambiguous	1.03	Ambiguous	0.38	Likely Benign	0.673	Likely Pathogenic	-4.82	Deleterious	0.987	Probably Damaging	0.990	Probably Damaging	-1.22	Pathogenic	0.06	Tolerated			0.0936	0.4879		2	1	0.0	-0.98
c.1460A>C	N487T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N487T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, 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, SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No evidence from FoldX, Rosetta, or premPS is available to alter this assessment. Overall, the preponderance of computational evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-12.618	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	1.92	Ambiguous	0.1	1.94	Ambiguous	1.93	Ambiguous	0.68	Ambiguous	0.481	Likely Benign	-5.97	Deleterious	0.987	Probably Damaging	0.980	Probably Damaging	2.78	Benign	0.05	Affected			0.1200	0.3441		0	0	2.8	-13.00
c.1481T>A	I494K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I494K is not reported in ClinVar (ClinVar ID None) 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 in the dataset predicts a benign outcome. High‑accuracy methods 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 unanimous computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.353330	Uncertain	0.941	0.157	0.000											-15.950	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	4.23	Destabilizing	0.2	5.33	Destabilizing	4.78	Destabilizing	1.89	Destabilizing	0.925	Likely Pathogenic	-6.40	Deleterious	0.987	Probably Damaging	0.937	Probably Damaging	-1.41	Pathogenic	0.00	Affected			0.1015	0.0870		-2	-3	-8.4	15.01
c.1525G>C	A509P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect, so the benign‑prediction group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect; 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 a pathogenic impact. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status (no report). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-13.234	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	5.82	Destabilizing	0.6	7.70	Destabilizing	6.76	Destabilizing	1.13	Destabilizing	0.884	Likely Pathogenic	-4.15	Deleterious	0.987	Probably Damaging	0.844	Possibly Damaging	-1.39	Pathogenic	0.01	Affected			0.1940	0.4570		1	-1	-3.4	26.04
c.1535A>C	E512A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain results come from Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show SGM‑Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-10.979	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.97	Ambiguous	0.71	Ambiguous	0.04	Likely Benign	0.309	Likely Benign	-5.71	Deleterious	0.987	Probably Damaging	0.937	Probably Damaging	3.31	Benign	0.12	Tolerated			0.4293	0.5162		0	-1	5.3	-58.04
c.1610C>A	A537E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537E is not 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, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; 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. No prediction or stability result is missing or inconclusive. Based on the overall consensus of the available tools, 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	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000											-5.120	Likely Benign	0.450	Ambiguous	Likely Benign	-0.14	Likely Benign	0.1	0.00	Likely Benign	-0.07	Likely Benign	0.23	Likely Benign	0.378	Likely Benign	-1.78	Neutral	0.987	Probably Damaging	0.838	Possibly Damaging	-1.04	Pathogenic	1.00	Tolerated			0.1347	0.1566		0	-1	-5.3	58.04
c.1634T>G	M545R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that classify the variant as benign include SIFT, FoldX, and Foldetta, 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. Rosetta’s assessment is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000											-9.223	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	-0.27	Likely Benign	0.1	0.95	Ambiguous	0.34	Likely Benign	1.07	Destabilizing	0.773	Likely Pathogenic	-4.76	Deleterious	0.987	Probably Damaging	0.971	Probably Damaging	-1.23	Pathogenic	0.36	Tolerated			0.1345	0.0837		0	-1	-6.4	24.99
c.1895A>T	N632I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N632I is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include premPS and Foldetta, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (likely pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, remains likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the preponderance of evidence points to a pathogenic classification for N632I, and this conclusion does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.041437	Uncertain	0.938	0.254	0.000											-12.620	Likely Pathogenic	0.881	Likely Pathogenic	Ambiguous	1.33	Ambiguous	0.3	-1.24	Ambiguous	0.05	Likely Benign	0.20	Likely Benign	0.839	Likely Pathogenic	-7.76	Deleterious	0.987	Probably Damaging	0.887	Possibly Damaging	-1.56	Pathogenic	0.02	Affected			0.0712	0.5973		-2	-3	8.0	-0.94
c.2092G>C	E698Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698Q is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. No prediction or folding stability result is missing or inconclusive. Overall, the evidence is split, with an equal number of benign and pathogenic calls; the high‑accuracy tools lean toward benign but are not definitive. Thus, the variant’s pathogenicity remains uncertain and does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-8.369	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	0.00	Likely Benign	0.1	0.35	Likely Benign	0.18	Likely Benign	-0.02	Likely Benign	0.326	Likely Benign	-2.86	Deleterious	0.987	Probably Damaging	0.946	Probably Damaging	3.35	Benign	0.01	Affected			0.1029	0.3702		2	2	0.0	-0.98
c.2180A>C	N727T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, Rosetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. FoldX gives an uncertain result and is therefore treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625											-6.900	Likely Benign	0.335	Likely Benign	Likely Benign	0.52	Ambiguous	0.1	-0.18	Likely Benign	0.17	Likely Benign	0.04	Likely Benign	0.125	Likely Benign	-3.08	Deleterious	0.987	Probably Damaging	0.980	Probably Damaging	2.25	Pathogenic	0.74	Tolerated			0.1315	0.7181		0	0	2.8	-13.00
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.3539T>A	L1180H 2D AIThe SynGAP1 missense variant L1180H is not reported in ClinVar and has no gnomAD allele, so its population frequency is unknown. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 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 highlight AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus leans benign; Foldetta results are not available. Overall, five of nine individual predictors favor pathogenicity, four favor benign, and the consensus tool suggests benign. Thus, the variant is most likely pathogenic based on the preponderance of high‑confidence predictions, and this assessment is not contradicted by ClinVar, which contains no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-5.621	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.213	Likely Benign	-0.22	Neutral	0.987	Probably Damaging	0.865	Possibly Damaging	2.65	Benign	0.00	Affected			0.0991	0.0860		-2	-3	-7.0	23.98
c.3632T>A	M1211K 2D AIThe SynGAP1 missense variant M1211K is listed in ClinVar (ID 834052.0) as benign and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FATHMM and AlphaMissense‑Optimized, while the remaining seven tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta data are unavailable. Overall, the preponderance of evidence from standard predictors and the SGM Consensus supports a pathogenic interpretation, which contradicts the benign classification reported in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500					Likely Benign		1				-9.013	Likely Pathogenic	0.662	Likely Pathogenic	Likely Benign										0.595	Likely Pathogenic	-2.95	Deleterious	0.987	Probably Damaging	0.979	Probably Damaging	5.59	Benign	0.01	Affected	3.77	5	0.1462	0.0879		0	-1	-5.8	-3.02
c.3632T>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.3632T>G	M1211R 2D AIThe SynGAP1 missense variant M1211R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are FATHMM and AlphaMissense‑Optimized, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500											-8.196	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign										0.587	Likely Pathogenic	-3.18	Deleterious	0.987	Probably Damaging	0.985	Probably Damaging	5.47	Benign	0.01	Affected			0.1644	0.0828		0	-1	-6.4	24.99
c.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.1193C>G	P398R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P398R variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include only FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—indicate a pathogenic effect, while Rosetta, premPS, and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.436924	Structured	0.401041	Uncertain	0.891	0.525	0.250											-9.575	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	3.01	Destabilizing	0.5	1.35	Ambiguous	2.18	Destabilizing	0.98	Ambiguous	0.755	Likely Pathogenic	-6.55	Deleterious	0.988	Probably Damaging	0.724	Possibly Damaging	5.49	Benign	0.00	Affected			0.1479	0.3472		0	-2	-2.9	59.07
c.1441C>T	H481Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H481Y is listed in ClinVar as benign (ClinVar ID 1543764.0) and is present in the gnomAD database (gnomAD ID 6‑33438473‑C‑T). Prediction tools that classify the variant as benign include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta report uncertain stability effects. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Taking all available evidence together, the variant is most likely benign, which is consistent with its ClinVar benign annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000					Likely Benign		1	6-33438473-C-T	16	9.91e-6	-10.910	Likely Pathogenic	0.565	Likely Pathogenic	Likely Benign	-0.53	Ambiguous	0.1	-0.46	Likely Benign	-0.50	Ambiguous	0.20	Likely Benign	0.256	Likely Benign	-3.32	Deleterious	0.988	Probably Damaging	0.979	Probably Damaging	3.40	Benign	0.59	Tolerated	3.37	33	0.0610	0.3558		0	2	1.9	26.03	256.5	-44.4	0.0	0.0	0.2	0.2	X			X				Uncertain	The imidazole ring of the His481 side chain is located in a short helical structure (res. Glu480-Leu482) within an α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. In the WT simulations, His481 alternately stacks against Arg485, Arg587, and Glu480 without a definite role. In the variant simulations, Tyr481 also alternately stacks with nearby arginine residues, including Arg485, Arg587, and Arg479. The interaction between Tyr481 and Arg479 affects the α-α loop, causing it to fold into a distorted helical structure, an effect that might be more pronounced during protein folding. Finally, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.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.1538T>A	F513Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F513Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT classifies it as benign, whereas REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenicity. Stability‑based methods (FoldX, Rosetta, Foldetta) and AlphaMissense‑Optimized return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as uncertain. With 10 of 12 evaluated tools indicating pathogenicity and no conflicting ClinVar annotation, the variant is most likely pathogenic, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.250651	Uncertain	0.949	0.269	0.000											-10.022	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	1.09	Ambiguous	0.2	1.03	Ambiguous	1.06	Ambiguous	1.09	Destabilizing	0.791	Likely Pathogenic	-2.92	Deleterious	0.988	Probably Damaging	0.976	Probably Damaging	-1.39	Pathogenic	0.07	Tolerated			0.1046	0.1087		7	3	-4.1	16.00
c.1682T>A	F561Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561Y is not reported in ClinVar 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; the remaining predictions (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) are uncertain or unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Based on the consensus of the majority of evidence‑based predictors, 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	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-12.692	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	1.54	Ambiguous	0.1	0.75	Ambiguous	1.15	Ambiguous	1.28	Destabilizing	0.693	Likely Pathogenic	-2.99	Deleterious	0.988	Probably Damaging	0.976	Probably Damaging	-1.34	Pathogenic	0.01	Affected			0.1344	0.1120		7	3	-4.1	16.00
c.1792C>A	L598I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L598I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and ESM1b. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign impact. This conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-9.396	Likely Pathogenic	0.512	Ambiguous	Likely Benign	0.80	Ambiguous	0.0	0.38	Likely Benign	0.59	Ambiguous	0.78	Ambiguous	0.246	Likely Benign	-1.96	Neutral	0.988	Probably Damaging	0.910	Probably Damaging	3.47	Benign	0.10	Tolerated			0.0792	0.2000		2	2	0.7	0.00
c.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.1981C>G	Q661E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Four tools (FoldX, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of available predictions lean toward a benign impact. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-12.121	Likely Pathogenic	0.370	Ambiguous	Likely Benign	0.64	Ambiguous	0.1	0.35	Likely Benign	0.50	Ambiguous	0.61	Ambiguous	0.141	Likely Benign	-2.15	Neutral	0.988	Probably Damaging	0.619	Possibly Damaging	3.42	Benign	0.03	Affected			0.1199	0.2439		2	2	0.0	0.98
c.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.2080G>C	A694P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, while the majority of other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as Likely Pathogenic, with three of four votes pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for A694P. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, and there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-10.569	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.39	Destabilizing	0.2	5.59	Destabilizing	4.49	Destabilizing	0.82	Ambiguous	0.209	Likely Benign	-2.77	Deleterious	0.988	Probably Damaging	0.578	Possibly Damaging	3.44	Benign	0.03	Affected			0.2265	0.3829		1	-1	-3.4	26.04
c.2123T>G	L708R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as Likely Pathogenic. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of tools (six pathogenic vs. four benign) and the SGM Consensus support a pathogenic classification, whereas AlphaMissense‑Optimized suggests benign. The variant is most likely pathogenic based on the collective predictions, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-9.154	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.0	0.90	Ambiguous	0.89	Ambiguous	1.24	Destabilizing	0.249	Likely Benign	-4.18	Deleterious	0.988	Probably Damaging	0.598	Possibly Damaging	3.27	Benign	0.19	Tolerated			0.1091	0.0488		-3	-2	-8.3	43.03
c.2393C>A	P798Q 2D AIThe SynGAP1 missense variant P798Q is 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. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P798Q, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.944	Likely Benign	0.074	Likely Benign	Likely Benign										0.068	Likely Benign	-0.53	Neutral	0.988	Probably Damaging	0.780	Possibly Damaging	4.25	Benign	0.00	Affected			0.1290	0.3864		0	-1	-1.9	31.01
c.3160G>C	G1054R 2D AIThe SynGAP1 missense variant G1054R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for G1054R, 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		0.983019	Disordered	0.878015	Binding	0.389	0.936	0.875											-8.863	Likely Pathogenic	0.326	Likely Benign	Likely Benign										0.234	Likely Benign	0.29	Neutral	0.988	Probably Damaging	0.589	Possibly Damaging	4.05	Benign	0.42	Tolerated			0.1164	0.4342		-3	-2	-4.1	99.14
c.3610T>C	S1204P 2D AIThe SynGAP1 missense variant S1204P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, 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, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for S1204P. This prediction 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.		Coiled-coil	0.595080	Disordered	0.541098	Binding	0.887	0.587	0.375											-14.031	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.502	Likely Pathogenic	-1.80	Neutral	0.988	Probably Damaging	0.856	Possibly Damaging	5.39	Benign	0.31	Tolerated			0.2139	0.3886		1	-1	-0.8	10.04
c.3920C>A	P1307Q 2D AIThe SynGAP1 missense variant P1307Q is listed in ClinVar (ID 982827.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451794‑C‑A). 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, PROVEAN). 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. This conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.798249	Disordered	0.913511	Binding	0.491	0.901	0.875					Uncertain		1	6-33451794-C-A			-4.227	Likely Benign	0.114	Likely Benign	Likely Benign										0.192	Likely Benign	-0.88	Neutral	0.988	Probably Damaging	0.765	Possibly Damaging	2.82	Benign	0.03	Affected	3.77	5	0.1629	0.4464		0	-1	-1.9	31.01
c.484C>T	R162C 2D AIThe SynGAP1 missense variant R162C is listed in ClinVar as Pathogenic and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the available predictions are split evenly between benign and pathogenic, with no single method providing decisive evidence. Thus, the variant’s pathogenicity remains uncertain based on computational predictions, which contradicts the ClinVar pathogenic classification. 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					Pathogenic		2				-8.157	Likely Pathogenic	0.787	Likely Pathogenic	Ambiguous										0.150	Likely Benign	-2.05	Neutral	0.988	Probably Damaging	0.513	Possibly Damaging	4.00	Benign	0.11	Tolerated	3.74	4	0.3364	0.4292		-4	-3	7.0	-53.05
c.1007A>T	K336M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS) and pathogenic predictions (SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled “Likely Pathogenic.” Stability‑based assessments are inconclusive: Foldetta is uncertain, and Rosetta is also uncertain. High‑accuracy tools specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms pathogenic, while Foldetta remains uncertain. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-15.395	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.34	Likely Benign	0.1	0.82	Ambiguous	0.58	Ambiguous	-0.23	Likely Benign	0.301	Likely Benign	-5.07	Deleterious	0.989	Probably Damaging	0.832	Possibly Damaging	1.53	Pathogenic	0.00	Affected			0.1185	0.4760		0	-1	5.8	3.02
c.1012G>T	D338Y 2D AIThe SynGAP1 D338Y missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree on a deleterious effect: premPS is the sole predictor labeling it benign, whereas the remaining seven tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—classify it as pathogenic. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is also uncertain. Overall, the preponderance of evidence indicates that D338Y 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	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-14.190	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	1.10	Ambiguous	1.3	0.91	Ambiguous	1.01	Ambiguous	0.22	Likely Benign	0.552	Likely Pathogenic	-6.49	Deleterious	0.989	Probably Damaging	0.832	Possibly Damaging	1.66	Pathogenic	0.00	Affected			0.0687	0.5609		-4	-3	2.2	48.09
c.1043T>A	V348E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348E is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among the majority of tools, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for V348E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-11.135	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.1	2.20	Destabilizing	2.31	Destabilizing	2.14	Destabilizing	0.470	Likely Benign	-5.26	Deleterious	0.989	Probably Damaging	0.637	Possibly Damaging	1.56	Pathogenic	0.01	Affected			0.1089	0.1922		-2	-2	-7.7	29.98
c.1094T>A	V365E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365E is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts pathogenic. With all available evidence pointing to a damaging effect and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-16.263	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	3.99	Destabilizing	0.3	3.81	Destabilizing	3.90	Destabilizing	2.20	Destabilizing	0.613	Likely Pathogenic	-5.02	Deleterious	0.989	Probably Damaging	0.688	Possibly Damaging	1.66	Pathogenic	0.00	Affected			0.0849	0.2083		-2	-2	-7.7	29.98
c.113C>A	P38Q 2D AIThe SynGAP1 missense variant P38Q is 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 P38Q, 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	0.433285	Uncertain	0.344	0.791	0.375											-3.520	Likely Benign	0.183	Likely Benign	Likely Benign										0.129	Likely Benign	-2.16	Neutral	0.989	Probably Damaging	0.975	Probably Damaging	4.00	Benign	0.00	Affected			0.1737	0.5521		0	-1	-1.9	31.01
c.113C>G	P38R 2D AIThe SynGAP1 missense variant P38R 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 points to a benign effect for P38R, 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		0.497853	Structured	0.433285	Uncertain	0.344	0.791	0.375											-1.799	Likely Benign	0.314	Likely Benign	Likely Benign										0.168	Likely Benign	-2.29	Neutral	0.989	Probably Damaging	0.975	Probably Damaging	4.00	Benign	0.00	Affected			0.1620	0.4060		0	-2	-2.9	59.07
c.1219C>G	Q407E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome. AlphaMissense‑Default, FoldX, Rosetta, and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools and the SGM Consensus support a pathogenic classification, while a minority predict benign. No ClinVar entry exists to contradict these predictions. 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.		C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-12.631	Likely Pathogenic	0.466	Ambiguous	Likely Benign	0.50	Ambiguous	0.1	1.68	Ambiguous	1.09	Ambiguous	1.30	Destabilizing	0.243	Likely Benign	-2.66	Deleterious	0.989	Probably Damaging	0.930	Probably Damaging	3.96	Benign	0.03	Affected			0.1199	0.2000		2	2	0.0	0.98
c.1416G>C	E472D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472D is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL and SIFT, whereas the majority of tools—SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict pathogenicity. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability estimates. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (derived from the four high‑confidence predictors) is pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E472D, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-9.798	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.27	Ambiguous	0.3	1.99	Ambiguous	1.63	Ambiguous	1.00	Destabilizing	0.304	Likely Benign	-2.75	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			0.1975	0.3918		3	2	0.0	-14.03
c.1416G>T	E472D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), FATHMM, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, Foldetta) yield uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000											-9.798	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.27	Ambiguous	0.3	1.99	Ambiguous	1.63	Ambiguous	1.00	Destabilizing	0.303	Likely Benign	-2.75	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			0.1975	0.3918		3	2	0.0	-14.03
c.1440G>C	E480D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E480D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, whereas polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact. The remaining tools—FoldX, Rosetta, premPS, AlphaMissense‑Default, and Foldetta—return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority, and Foldetta remains uncertain. Overall, the balance of evidence favors a benign classification for E480D, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-3.001	Likely Benign	0.475	Ambiguous	Likely Benign	0.62	Ambiguous	0.2	1.39	Ambiguous	1.01	Ambiguous	0.61	Ambiguous	0.405	Likely Benign	-0.77	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.28	Tolerated			0.1526	0.4130		3	2	0.0	-14.03
c.1440G>T	E480D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E480D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic outcome. The remaining tools—FoldX, Rosetta, premPS, AlphaMissense‑Default, and Foldetta—return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward benign, and Foldetta providing no definitive stability change. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000											-3.001	Likely Benign	0.475	Ambiguous	Likely Benign	0.62	Ambiguous	0.2	1.39	Ambiguous	1.01	Ambiguous	0.61	Ambiguous	0.405	Likely Benign	-0.77	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.28	Tolerated			0.1526	0.4130		3	2	0.0	-14.03
c.1444C>G	L482V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include 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 impact. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.676	Likely Pathogenic	0.734	Likely Pathogenic	Likely Benign	1.97	Ambiguous	0.1	1.52	Ambiguous	1.75	Ambiguous	0.76	Ambiguous	0.709	Likely Pathogenic	-2.95	Deleterious	0.989	Probably Damaging	0.984	Probably Damaging	-1.30	Pathogenic	0.10	Tolerated			0.1074	0.2027		2	1	0.4	-14.03
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.1557A>C	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven benign predictions versus six pathogenic ones, the overall evidence slightly favors a benign classification. This conclusion does not contradict the ClinVar status, which contains no pathogenic assertion for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.183	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1557A>T	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E519D is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign interpretation. This consensus does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.182	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1568A>T	N523I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N523I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools report uncertain results: Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains inconclusive. Overall, the preponderance of evidence (eight pathogenic versus three benign predictions) suggests 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	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125											-12.862	Likely Pathogenic	0.761	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	-1.53	Ambiguous	-0.64	Ambiguous	0.33	Likely Benign	0.726	Likely Pathogenic	-8.18	Deleterious	0.989	Probably Damaging	0.946	Probably Damaging	-1.42	Pathogenic	0.00	Affected			0.0627	0.3714		-2	-3	8.0	-0.94
c.1575G>C	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are therefore not used to weigh the overall assessment. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, while Foldetta predicts benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for E525D. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.1575G>T	E525D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E525D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and Foldetta, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX and Rosetta provide uncertain results and are not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the balance of evidence (nine pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-11.207	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	0.362	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			0.1876	0.2197		3	2	0.0	-14.03
c.1734G>C	E578D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E578D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign (2 benign vs 1 pathogenic votes), and Foldetta also predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-4.366	Likely Benign	0.447	Ambiguous	Likely Benign	0.46	Likely Benign	0.1	0.15	Likely Benign	0.31	Likely Benign	-0.05	Likely Benign	0.318	Likely Benign	-0.53	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.43	Pathogenic	0.33	Tolerated			0.1561	0.3554		3	2	0.0	-14.03
c.1734G>T	E578D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E578D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign (2 benign vs 1 pathogenic votes), and Foldetta predicts a benign stability change. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-4.366	Likely Benign	0.447	Ambiguous	Likely Benign	0.46	Likely Benign	0.1	0.15	Likely Benign	0.31	Likely Benign	-0.05	Likely Benign	0.318	Likely Benign	-0.53	Neutral	0.989	Probably Damaging	0.979	Probably Damaging	-1.43	Pathogenic	0.33	Tolerated			0.1561	0.3554		3	2	0.0	-14.03
c.1839G>C	E613D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E613D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Three tools—FoldX, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: 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 uncertain. Overall, the majority of evidence points to a pathogenic impact for E613D. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-8.795	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.67	Ambiguous	0.3	0.48	Likely Benign	0.58	Ambiguous	0.13	Likely Benign	0.474	Likely Benign	-2.79	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.15	Tolerated			0.1998	0.4000		3	2	0.0	-14.03
c.1839G>T	E613D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E613D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Three tools—FoldX, Foldetta, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: 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 uncertain. Overall, the majority of evidence points to a pathogenic impact for E613D. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-8.795	Likely Pathogenic	0.842	Likely Pathogenic	Ambiguous	0.67	Ambiguous	0.3	0.48	Likely Benign	0.58	Ambiguous	0.13	Likely Benign	0.474	Likely Benign	-2.79	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.15	Tolerated			0.1998	0.4000		3	2	0.0	-14.03
c.1972G>T	G658C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. One tool, ESM1b, yields an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign (2 benign vs. 1 pathogenic, 1 uncertain), and Foldetta predicts a benign impact on protein stability. Overall, the majority of evidence points to a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000											-7.577	In-Between	0.170	Likely Benign	Likely Benign	0.05	Likely Benign	0.0	0.04	Likely Benign	0.05	Likely Benign	0.46	Likely Benign	0.146	Likely Benign	-3.49	Deleterious	0.989	Probably Damaging	0.544	Possibly Damaging	3.37	Benign	0.04	Affected			0.1509	0.3141		-3	-3	2.9	46.09
c.209G>C	R70P 2D AIThe SynGAP1 missense variant R70P 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 effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.458981	Uncertain	0.392	0.793	0.375											-2.914	Likely Benign	0.633	Likely Pathogenic	Likely Benign										0.170	Likely Benign	-1.33	Neutral	0.989	Probably Damaging	0.859	Possibly Damaging	4.08	Benign	0.00	Affected			0.1903	0.4304		0	-2	2.9	-59.07
c.2104C>G	Q702E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta give uncertain results. High‑accuracy methods further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign; Foldetta remains inconclusive. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-10.974	Likely Pathogenic	0.230	Likely Benign	Likely Benign	0.48	Likely Benign	0.0	0.72	Ambiguous	0.60	Ambiguous	0.27	Likely Benign	0.196	Likely Benign	-2.27	Neutral	0.989	Probably Damaging	0.930	Probably Damaging	3.55	Benign	0.15	Tolerated			0.1021	0.1609		2	2	0.0	0.98
c.2228C>A	P743H 2D AIThe SynGAP1 missense variant P743H 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 overall assessment. Overall, the majority of computational evidence points to a benign effect for P743H, 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		0.852992	Disordered	0.526809	Binding	0.317	0.862	0.875											-5.649	Likely Benign	0.099	Likely Benign	Likely Benign										0.121	Likely Benign	-1.99	Neutral	0.989	Probably Damaging	0.870	Possibly Damaging	2.70	Benign	0.01	Affected			0.1653	0.3762		0	-2	-1.6	40.02
c.2302G>T	D768Y 2D AIThe SynGAP1 missense variant D768Y is listed in ClinVar with status “Uncertain” (ClinVar ID 1061652.0) and is present in gnomAD (variant ID 6‑33442460‑G‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar designation of uncertainty. Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250					Uncertain		1	6-33442460-G-T			-9.866	Likely Pathogenic	0.824	Likely Pathogenic	Ambiguous										0.234	Likely Benign	-2.86	Deleterious	0.989	Probably Damaging	0.806	Possibly Damaging	4.01	Benign	0.07	Tolerated	3.64	6	0.0581	0.7525		-4	-3	2.2	48.09
c.2419T>C	Y807H 2D AIThe SynGAP1 missense variant Y807H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as pathogenic. AlphaMissense‑Optimized remains benign, while Foldetta results are unavailable. Overall, the majority of high‑accuracy and consensus predictors (five out of six) suggest a pathogenic impact, whereas only three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, 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.		SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-5.879	Likely Benign	0.413	Ambiguous	Likely Benign										0.152	Likely Benign	-2.74	Deleterious	0.989	Probably Damaging	0.913	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.2530	0.0704		0	2	-1.9	-26.03
c.2434C>G	P812A 2D AIThe SynGAP1 missense variant P812A is 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, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized 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 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	SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.113	Likely Benign	0.275	Likely Benign	Likely Benign										0.137	Likely Benign	-1.49	Neutral	0.989	Probably Damaging	0.869	Possibly Damaging	2.75	Benign	0.08	Tolerated			0.3555	0.5350		1	-1	3.4	-26.04
c.2452C>T	P818S 2D AIThe SynGAP1 missense variant P818S is catalogued in gnomAD (ID 6‑33443004‑C‑T) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments are limited: AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. Taken together, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625								6-33443004-C-T	1	6.20e-7	-5.740	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-4.38	Deleterious	0.989	Probably Damaging	0.824	Possibly Damaging	2.04	Pathogenic	0.04	Affected	3.77	5	0.3581	0.6199		-1	1	0.8	-10.04
c.251G>C	R84P 2D AIThe SynGAP1 missense variant R84P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b is uncertain and does not influence the consensus. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R84P 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.			0.666105	Disordered	0.529205	Binding	0.298	0.888	0.500											-7.959	In-Between	0.994	Likely Pathogenic	Likely Pathogenic										0.157	Likely Benign	-2.50	Deleterious	0.989	Probably Damaging	0.859	Possibly Damaging	3.67	Benign	0.00	Affected			0.1978	0.4231		0	-2	2.9	-59.07
c.2707G>A	G903S 2D AIThe SynGAP1 missense variant G903S is reported in gnomAD (variant ID 6-33443259‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which labels the variant as “Likely Benign.” Pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus 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 G903S, and 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 Benign		0.680603	Disordered	0.549818	Binding	0.291	0.917	0.375								6-33443259-G-A	1	6.20e-7	-3.451	Likely Benign	0.154	Likely Benign	Likely Benign										0.091	Likely Benign	-1.37	Neutral	0.989	Probably Damaging	0.871	Possibly Damaging	2.40	Pathogenic	0.04	Affected	3.77	5	0.2447	0.4774		0	1	-0.4	30.03
c.2708G>C	G903A 2D AIThe SynGAP1 missense variant G903A is 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, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 not available. Overall, the majority of evidence points to a benign impact for G903A. 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		0.680603	Disordered	0.549818	Binding	0.291	0.917	0.375											-2.843	Likely Benign	0.227	Likely Benign	Likely Benign										0.141	Likely Benign	-1.54	Neutral	0.989	Probably Damaging	0.829	Possibly Damaging	2.43	Pathogenic	0.08	Tolerated			0.3490	0.5025		1	0	2.2	14.03
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.2757G>C	Q919H 2D AIThe SynGAP1 missense variant Q919H has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, 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, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.911223	Binding	0.299	0.841	0.250											-3.867	Likely Benign	0.237	Likely Benign	Likely Benign										0.153	Likely Benign	-1.83	Neutral	0.989	Probably Damaging	0.883	Possibly Damaging	2.39	Pathogenic	0.03	Affected			0.1463	0.4203		3	0	0.3	9.01
c.2757G>T	Q919H 2D AIThe SynGAP1 missense variant Q919H has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, 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, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.911223	Binding	0.299	0.841	0.250											-3.867	Likely Benign	0.237	Likely Benign	Likely Benign										0.152	Likely Benign	-1.83	Neutral	0.989	Probably Damaging	0.883	Possibly Damaging	2.39	Pathogenic	0.03	Affected			0.1463	0.4203		3	0	0.3	9.01
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.2760A>C	Q920H 2D AIThe SynGAP1 missense variant Q920H is 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. Based on the collective evidence, 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		0.699094	Disordered	0.927260	Binding	0.306	0.845	0.250											-3.771	Likely Benign	0.254	Likely Benign	Likely Benign										0.079	Likely Benign	-1.79	Neutral	0.989	Probably Damaging	0.883	Possibly Damaging	2.63	Benign	0.00	Affected			0.1419	0.4334		3	0	0.3	9.01
c.2760A>T	Q920H 2D AIThe SynGAP1 missense variant Q920H is 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. Based on the collective evidence, 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		0.699094	Disordered	0.927260	Binding	0.306	0.845	0.250											-3.771	Likely Benign	0.254	Likely Benign	Likely Benign										0.079	Likely Benign	-1.79	Neutral	0.989	Probably Damaging	0.883	Possibly Damaging	2.63	Benign	0.00	Affected			0.1419	0.4334		3	0	0.3	9.01
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.3087G>C	Q1029H 2D AIThe SynGAP1 missense variant Q1029H is 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, 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. This conclusion is consistent with the lack of ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500											-3.984	Likely Benign	0.308	Likely Benign	Likely Benign										0.041	Likely Benign	-0.83	Neutral	0.989	Probably Damaging	0.879	Possibly Damaging	2.74	Benign	0.15	Tolerated			0.1268	0.4184		3	0	0.3	9.01
c.3087G>T	Q1029H 2D AIThe SynGAP1 missense variant Q1029H 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 assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of the available predictions 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		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500											-3.984	Likely Benign	0.308	Likely Benign	Likely Benign										0.041	Likely Benign	-0.83	Neutral	0.989	Probably Damaging	0.879	Possibly Damaging	2.74	Benign	0.15	Tolerated			0.1268	0.4184		3	0	0.3	9.01
c.3408G>C	Q1136H 2D AIThe SynGAP1 missense variant Q1136H is 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 (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. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1136H, 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											-5.658	Likely Benign	0.305	Likely Benign	Likely Benign										0.347	Likely Benign	-1.98	Neutral	0.989	Probably Damaging	0.879	Possibly Damaging	5.42	Benign	0.03	Affected	4.32	2	0.1482	0.4637		0	3	0.3	9.01
c.3408G>T	Q1136H 2D AIThe SynGAP1 missense variant Q1136H is reported in gnomAD (variant ID 6-33443960‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict 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 further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus itself is 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 is not contradicted by any ClinVar classification (none is present). 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								6-33443960-G-T			-5.658	Likely Benign	0.305	Likely Benign	Likely Benign										0.347	Likely Benign	-1.98	Neutral	0.989	Probably Damaging	0.879	Possibly Damaging	5.42	Benign	0.03	Affected	4.32	2	0.1482	0.4637		0	3	0.3	9.01
c.3501C>A	D1167E 2D AIThe SynGAP1 missense variant D1167E is 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 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 balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.908	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.141	Likely Benign	-1.19	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	2.57	Benign	0.24	Tolerated			0.1468	0.7368		3	2	0.0	14.03
c.3501C>G	D1167E 2D AIThe SynGAP1 missense variant D1167E is 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 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 balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.908	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-1.19	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	2.57	Benign	0.24	Tolerated			0.1468	0.7368		3	2	0.0	14.03
c.3507G>C	E1169D 2D AIThe SynGAP1 missense variant E1169D is not 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 and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of consensus tools predict a pathogenic impact, and no ClinVar entry contradicts this assessment. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625											-3.457	Likely Benign	0.913	Likely Pathogenic	Ambiguous										0.104	Likely Benign	-1.12	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1597	0.3968		3	2	0.0	-14.03
c.3507G>T	E1169D 2D AIThe SynGAP1 missense variant E1169D is not 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 and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of consensus tools predict a pathogenic impact, and no ClinVar entry contradicts this assessment. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625											-3.457	Likely Benign	0.913	Likely Pathogenic	Ambiguous										0.103	Likely Benign	-1.12	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1597	0.3968		3	2	0.0	-14.03
c.3528A>C	E1176D 2D AIThe SynGAP1 E1176D missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.572075	Binding	0.525	0.715	0.250											-4.603	Likely Benign	0.731	Likely Pathogenic	Likely Benign										0.322	Likely Benign	-0.81	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	5.44	Benign	0.31	Tolerated			0.1419	0.4026		3	2	0.0	-14.03
c.3528A>T	E1176D 2D AIThe SynGAP1 missense variant E1176D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.572075	Binding	0.525	0.715	0.250											-4.603	Likely Benign	0.731	Likely Pathogenic	Likely Benign										0.322	Likely Benign	-0.81	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	5.44	Benign	0.31	Tolerated			0.1419	0.4026		3	2	0.0	-14.03
c.3586A>C	K1196Q 2D AIThe SynGAP1 missense variant K1196Q is not reported in ClinVar and has no entry in gnomAD. 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 of AlphaMissense‑Default, ESM1b, FATHMM, 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. 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 (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-5.222	Likely Benign	0.346	Ambiguous	Likely Benign										0.342	Likely Benign	-0.65	Neutral	0.989	Probably Damaging	0.819	Possibly Damaging	5.38	Benign	0.07	Tolerated			0.3814	0.0945		1	1	0.4	-0.04
c.3619G>C	E1207Q 2D AIThe SynGAP1 missense variant E1207Q is not 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 outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta results are unavailable. Taken together, the majority of evidence points to a benign effect, and this conclusion does not conflict with any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.604312	Disordered	0.562696	Binding	0.912	0.571	0.375											-6.789	Likely Benign	0.538	Ambiguous	Likely Benign										0.167	Likely Benign	-1.95	Neutral	0.989	Probably Damaging	0.904	Possibly Damaging	2.11	Pathogenic	0.03	Affected			0.0808	0.4185		2	2	0.0	-0.98
c.3620A>C	E1207A 2D AIThe SynGAP1 missense variant E1207A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized indicates a benign effect, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence points to a pathogenic effect for E1207A, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.562696	Binding	0.912	0.571	0.375											-8.277	Likely Pathogenic	0.679	Likely Pathogenic	Likely Benign										0.295	Likely Benign	-4.27	Deleterious	0.989	Probably Damaging	0.829	Possibly Damaging	2.11	Pathogenic	0.02	Affected			0.3019	0.4305		0	-1	5.3	-58.04
c.3671T>G	L1224R 2D AIThe SynGAP1 missense variant L1224R is listed in ClinVar with no assertion (ClinVar status: None) and is present in the gnomAD database (ID 6‑33446663‑T‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500								6-33446663-T-G	1	6.20e-7	-7.504	In-Between	0.220	Likely Benign	Likely Benign										0.113	Likely Benign	-1.85	Neutral	0.989	Probably Damaging	0.900	Possibly Damaging	2.42	Pathogenic	0.33	Tolerated	3.77	5	0.1120	0.0558		-2	-3	-8.3	43.03
c.3770C>A	S1257Y 2D AIThe SynGAP1 missense variant S1257Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; 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) leans pathogenic (2 pathogenic vs 1 benign). Foldetta results are unavailable. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) indicate a pathogenic impact. 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.		Coiled-coil	0.541878	Disordered	0.482380	Uncertain	0.889	0.572	0.375											-8.632	Likely Pathogenic	0.399	Ambiguous	Likely Benign										0.120	Likely Benign	-2.65	Deleterious	0.989	Probably Damaging	0.883	Possibly Damaging	2.55	Benign	0.03	Affected			0.0480	0.4463		-3	-2	-0.5	76.10
c.379C>T	R127W 2D AISynGAP1 missense variant R127W is listed in ClinVar with an Uncertain significance status and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Consequently, the evidence does not favor a clear benign or pathogenic outcome; the predictions are balanced and align with the ClinVar designation of Uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.711716	Binding	0.333	0.870	0.625					Uncertain		1				-4.776	Likely Benign	0.806	Likely Pathogenic	Ambiguous										0.118	Likely Benign	-2.98	Deleterious	0.989	Probably Damaging	0.420	Benign	3.88	Benign	0.00	Affected			0.1583	0.3005		2	-3	3.6	30.03
c.575C>G	A192G 2D AIThe SynGAP1 missense variant A192G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, 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. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-9.003	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous										0.133	Likely Benign	-3.00	Deleterious	0.989	Probably Damaging	0.621	Possibly Damaging	3.91	Benign	0.02	Affected			0.2081	0.2857		1	0	-2.2	-14.03
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.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.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.648G>C	Q216H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas those that predict a pathogenic impact are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.532	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	0.638	Likely Pathogenic	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			0.1909	0.4660		3	0	0.3	9.01
c.648G>T	Q216H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.532	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	0.638	Likely Pathogenic	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			0.1909	0.4660		3	0	0.3	9.01
c.866T>G	M289R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M289R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No predictions or stability results are missing or inconclusive. Overall, the majority of tools lean toward a pathogenic effect, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000											-11.090	Likely Pathogenic	0.719	Likely Pathogenic	Likely Benign	0.04	Likely Benign	0.1	0.28	Likely Benign	0.16	Likely Benign	1.01	Destabilizing	0.228	Likely Benign	-2.84	Deleterious	0.989	Probably Damaging	0.767	Possibly Damaging	1.84	Pathogenic	0.08	Tolerated			0.1482	0.0828		0	-1	-6.4	24.99
c.956C>T	A319V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A319V 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, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also inconclusive. Overall, the majority of evidence points to a benign effect, and this 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.		C2	0.179055	Structured	0.410405	Uncertain	0.879	0.254	0.125											-8.179	Likely Pathogenic	0.141	Likely Benign	Likely Benign	0.58	Ambiguous	0.4	0.63	Ambiguous	0.61	Ambiguous	0.23	Likely Benign	0.329	Likely Benign	-2.32	Neutral	0.989	Probably Damaging	0.824	Possibly Damaging	1.88	Pathogenic	0.10	Tolerated			0.1094	0.6390		0	0	2.4	28.05
c.1688G>A	R563K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R563K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are inconclusive are Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-10.948	Likely Pathogenic	0.335	Likely Benign	Likely Benign	0.25	Likely Benign	0.0	0.66	Ambiguous	0.46	Likely Benign	0.70	Ambiguous	0.198	Likely Benign	-2.37	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	3.46	Benign	0.35	Tolerated			0.4434	0.2379		3	2	0.6	-28.01
c.1761G>C	R587S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R587S is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: the single benign prediction comes from SIFT, while the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus—indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; AlphaMissense‑Optimized is “Uncertain”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also “Uncertain.” Taken together, the preponderance of evidence points to a pathogenic impact for R587S. 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	0.054297	Structured	0.077330	Uncertain	0.862	0.216	0.000											-12.264	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.84	Ambiguous	0.1	1.79	Ambiguous	1.32	Ambiguous	1.17	Destabilizing	0.508	Likely Pathogenic	-4.84	Deleterious	0.990	Probably Damaging	0.779	Possibly Damaging	-1.20	Pathogenic	0.09	Tolerated	3.37	35	0.2852	0.4165		-1	0	3.7	-69.11
c.1761G>T	R587S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R587S missense variant is catalogued in gnomAD (ID 6‑33440813‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default, while only SIFT predicts a benign outcome. Uncertain results are reported by FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized remains uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic, and Foldetta likewise yields an uncertain stability change. Overall, the preponderance of evidence indicates that R587S 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	0.054297	Structured	0.077330	Uncertain	0.862	0.216	0.000								6-33440813-G-T	4	2.48e-6	-12.264	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.84	Ambiguous	0.1	1.79	Ambiguous	1.32	Ambiguous	1.17	Destabilizing	0.508	Likely Pathogenic	-4.84	Deleterious	0.990	Probably Damaging	0.779	Possibly Damaging	-1.20	Pathogenic	0.09	Tolerated	3.37	35	0.2852	0.4165		-1	0	3.7	-69.11
c.2177G>A	R726K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-5.344	Likely Benign	0.231	Likely Benign	Likely Benign	0.28	Likely Benign	0.0	-0.02	Likely Benign	0.13	Likely Benign	0.20	Likely Benign	0.154	Likely Benign	-0.63	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	2.67	Benign	0.16	Tolerated			0.4920	0.4042		3	2	0.6	-28.01
c.2199G>C	Q733H 2D AIThe SynGAP1 missense variant Q733H is 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is 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		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875											-5.741	Likely Benign	0.207	Likely Benign	Likely Benign										0.140	Likely Benign	-2.47	Neutral	0.990	Probably Damaging	0.780	Possibly Damaging	2.52	Benign	0.02	Affected			0.1341	0.2263		3	0	0.3	9.01
c.2199G>T	Q733H 2D AIThe SynGAP1 missense variant Q733H is 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 Q733H, 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		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875											-5.741	Likely Benign	0.207	Likely Benign	Likely Benign										0.140	Likely Benign	-2.47	Neutral	0.990	Probably Damaging	0.780	Possibly Damaging	2.52	Benign	0.02	Affected			0.1341	0.2263		3	0	0.3	9.01
c.2297C>A	S766Y 2D AIThe SynGAP1 missense variant S766Y is reported in gnomAD (ID 6‑33442455‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) predicts pathogenic, and no Foldetta stability data are available. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250								6-33442455-C-A			-8.636	Likely Pathogenic	0.641	Likely Pathogenic	Likely Benign										0.222	Likely Benign	-2.67	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	4.09	Benign	0.00	Affected	3.64	6	0.0794	0.5609		-2	-3	-0.5	76.10
c.2297C>T	S766F 2D AIThe SynGAP1 missense variant S766F is listed in gnomAD (ID 6‑33442455‑C‑T) but has no ClinVar entry. Functional prediction tools show a split verdict: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250								6-33442455-C-T			-8.944	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign										0.233	Likely Benign	-2.87	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	4.08	Benign	0.00	Affected	3.64	6	0.0770	0.5887		-2	-3	3.6	60.10
c.2312C>A	S771Y 2D AIThe SynGAP1 missense variant S771Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-7.041	In-Between	0.397	Ambiguous	Likely Benign										0.176	Likely Benign	-2.13	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	4.02	Benign	0.05	Affected			0.0707	0.5155		-3	-2	-0.5	76.10
c.2312C>G	S771C 2D AIThe SynGAP1 missense variant S771C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is 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		0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-8.014	Likely Pathogenic	0.167	Likely Benign	Likely Benign										0.177	Likely Benign	-1.99	Neutral	0.990	Probably Damaging	0.917	Probably Damaging	4.01	Benign	0.07	Tolerated			0.1022	0.5899		0	-1	3.3	16.06
c.2312C>T	S771F 2D AIThe SynGAP1 missense variant S771F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-7.988	In-Between	0.525	Ambiguous	Likely Benign										0.189	Likely Benign	-2.29	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	4.02	Benign	0.04	Affected			0.0624	0.5428		-3	-2	3.6	60.10
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.2446T>A	S816T 2D AIThe SynGAP1 missense variant S816T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default 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 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 (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-3.957	Likely Benign	0.408	Ambiguous	Likely Benign										0.064	Likely Benign	-1.05	Neutral	0.990	Probably Damaging	0.846	Possibly Damaging	2.65	Benign	0.32	Tolerated			0.1573	0.5529		1	1	0.1	14.03
c.2449T>A	S817T 2D AIThe SynGAP1 missense variant S817T is not 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 agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign, and Foldetta results are unavailable. Overall, the balance of evidence from both general and high‑accuracy predictors points to a benign impact for S817T. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-6.544	Likely Benign	0.492	Ambiguous	Likely Benign										0.157	Likely Benign	-1.95	Neutral	0.990	Probably Damaging	0.846	Possibly Damaging	2.43	Pathogenic	0.00	Affected			0.1622	0.6482		1	1	0.1	14.03
c.2459A>T	Y820F 2D AIThe SynGAP1 missense variant Y820F is 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, 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 Y820F, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-4.686	Likely Benign	0.301	Likely Benign	Likely Benign										0.111	Likely Benign	-1.67	Neutral	0.990	Probably Damaging	0.893	Possibly Damaging	2.69	Benign	0.21	Tolerated			0.2398	0.2636		7	3	4.1	-16.00
c.2498A>C	K833T 2D AIThe SynGAP1 missense variant K833T is 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 polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic outcome. 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 independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the aggregate predictions, K833T 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		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-1.741	Likely Benign	0.481	Ambiguous	Likely Benign										0.142	Likely Benign	-1.65	Neutral	0.990	Probably Damaging	0.921	Probably Damaging	2.60	Benign	0.02	Affected			0.1848	0.3335		0	-1	3.2	-27.07
c.2506A>C	S836R 2D AIThe SynGAP1 missense variant S836R is 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 polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. 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 Uncertain, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence (five benign versus three pathogenic predictions, with the high‑accuracy consensus leaning benign) indicates that the variant is most likely benign. 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 Benign		0.525368	Disordered	0.634582	Binding	0.269	0.859	0.250											-6.050	Likely Benign	0.935	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-2.06	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.54	Benign	0.08	Tolerated			0.0731	0.3210		0	-1	-3.7	69.11
c.2508T>A	S836R 2D AIThe SynGAP1 missense variant S836R is 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 SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote) as Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. 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											-6.050	Likely Benign	0.935	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-2.06	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.54	Benign	0.08	Tolerated			0.0731	0.3210		0	-1	-3.7	69.11
c.2508T>G	S836R 2D AIThe SynGAP1 missense variant S836R is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in silico predictors shows a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Grouping by agreement, the benign‑predicating tools outnumber the pathogenic ones. 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) is classified as Likely Benign, and no Foldetta stability data are available. Overall, the preponderance of evidence leans toward a benign effect for S836R, 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		0.525368	Disordered	0.634582	Binding	0.269	0.859	0.250											-6.050	Likely Benign	0.935	Likely Pathogenic	Ambiguous										0.159	Likely Benign	-2.06	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.54	Benign	0.08	Tolerated			0.0731	0.3210		0	-1	-3.7	69.11
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.2541G>C	Q847H 2D AIThe SynGAP1 missense variant Q847H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) and the SGM‑Consensus result point to a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-4.208	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-2.82	Deleterious	0.990	Probably Damaging	0.925	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.1429	0.3634		3	0	0.3	9.01
c.2541G>T	Q847H 2D AIThe SynGAP1 missense variant Q847H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) and the SGM‑Consensus support a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-4.208	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-2.82	Deleterious	0.990	Probably Damaging	0.925	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.1429	0.3634		3	0	0.3	9.01
c.2566A>C	N856H 2D AIThe SynGAP1 missense variant N856H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. 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, 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, 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, suggest that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-2.596	Likely Benign	0.100	Likely Benign	Likely Benign										0.059	Likely Benign	-1.26	Neutral	0.990	Probably Damaging	0.923	Probably Damaging	4.10	Benign	0.09	Tolerated			0.1674	0.7495		2	1	0.3	23.04
c.2566A>T	N856Y 2D AIThe SynGAP1 missense variant N856Y is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional 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 for this variant. Overall, the majority of evidence points to a benign effect, 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		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500											-3.758	Likely Benign	0.189	Likely Benign	Likely Benign										0.152	Likely Benign	-2.45	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	4.07	Benign	0.05	Affected			0.0663	0.6309		-2	-2	2.2	49.07
c.2600G>C	G867A 2D AIThe SynGAP1 missense variant G867A is 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 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		0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250											-4.638	Likely Benign	0.172	Likely Benign	Likely Benign										0.081	Likely Benign	-1.18	Neutral	0.990	Probably Damaging	0.828	Possibly Damaging	2.79	Benign	0.94	Tolerated			0.3666	0.5534		1	0	2.2	14.03
c.2606T>C	L869P 2D AIThe SynGAP1 missense variant L869P is 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 polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification, and AlphaMissense‑Optimized independently 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—including the high‑accuracy tools—supports a benign interpretation. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.688653	Binding	0.272	0.839	0.250											-2.394	Likely Benign	0.523	Ambiguous	Likely Benign										0.174	Likely Benign	-0.99	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	2.58	Benign	0.04	Affected			0.3687	0.1503		-3	-3	-5.4	-16.04
c.2641T>A	L881M 2D AIThe SynGAP1 missense variant L881M is 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 of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. 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		0.703578	Disordered	0.629350	Binding	0.299	0.874	0.250											-4.419	Likely Benign	0.090	Likely Benign	Likely Benign										0.045	Likely Benign	-0.31	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.49	Pathogenic	0.03	Affected			0.0807	0.3997		4	2	-1.9	18.03
c.2668C>A	R890S 2D AIThe SynGAP1 missense variant R890S is 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. 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 (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. There is no ClinVar entry to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625											-2.481	Likely Benign	0.600	Likely Pathogenic	Likely Benign										0.176	Likely Benign	-1.73	Neutral	0.990	Probably Damaging	0.894	Possibly Damaging	4.02	Benign	0.27	Tolerated			0.3477	0.2875		0	-1	3.7	-69.11
c.2668C>G	R890G 2D AIThe SynGAP1 missense variant R890G is 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 outcome. 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 R890G 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		0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625											-2.080	Likely Benign	0.310	Likely Benign	Likely Benign										0.146	Likely Benign	-1.99	Neutral	0.990	Probably Damaging	0.894	Possibly Damaging	3.97	Benign	0.33	Tolerated			0.3734	0.2711		-3	-2	4.1	-99.14
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.2672T>C	L891P 2D AIThe SynGAP1 missense variant L891P 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. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for L891P, 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		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750											-3.835	Likely Benign	0.169	Likely Benign	Likely Benign										0.126	Likely Benign	-1.61	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	2.67	Benign	0.01	Affected			0.3594	0.1138		-3	-3	-5.4	-16.04
c.2689T>C	S897P 2D AIThe SynGAP1 missense variant S897P 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 not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.418474	Uncertain	0.292	0.928	0.500											-4.088	Likely Benign	0.216	Likely Benign	Likely Benign										0.097	Likely Benign	-0.21	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.64	Benign	0.04	Affected			0.2014	0.5933		1	-1	-0.8	10.04
c.2810A>G	D937G 2D AIThe SynGAP1 missense variant D937G is 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 outcome. 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 prediction is available, so it does not influence the assessment. Overall, the majority of evidence indicates that D937G 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		0.819762	Disordered	0.963385	Binding	0.348	0.883	0.625											-0.770	Likely Benign	0.301	Likely Benign	Likely Benign										0.155	Likely Benign	-0.93	Neutral	0.990	Probably Damaging	0.817	Possibly Damaging	2.82	Benign	0.72	Tolerated			0.4313	0.7006		1	-1	3.1	-58.04
c.2811T>A	D937E 2D AIThe SynGAP1 missense variant D937E 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 change as benign. Only the two polyPhen‑2 implementations (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 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 majority of prediction tools 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		0.819762	Disordered	0.963385	Binding	0.348	0.883	0.625											-3.342	Likely Benign	0.216	Likely Benign	Likely Benign										0.051	Likely Benign	-1.07	Neutral	0.990	Probably Damaging	0.801	Possibly Damaging	2.76	Benign	0.15	Tolerated			0.2524	0.6915		3	2	0.0	14.03
c.2811T>G	D937E 2D AIThe SynGAP1 D937E 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, 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. 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 (none is available). 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											-3.342	Likely Benign	0.216	Likely Benign	Likely Benign										0.051	Likely Benign	-1.07	Neutral	0.990	Probably Damaging	0.801	Possibly Damaging	2.76	Benign	0.15	Tolerated			0.2524	0.6915		3	2	0.0	14.03
c.2929G>C	A977P 2D AIThe SynGAP1 missense variant A977P is 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 A977P, 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	0.975330	Binding	0.306	0.884	0.625											-2.665	Likely Benign	0.135	Likely Benign	Likely Benign										0.094	Likely Benign	-1.12	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	3.94	Benign	0.02	Affected			0.2405	0.5212		1	-1	-3.4	26.04
c.2930C>A	A977D 2D AIThe SynGAP1 missense variant A977D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign, while Foldetta’s protein‑folding stability assessment is unavailable. Overall, the majority of evidence points to a benign impact for A977D, 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		0.882776	Disordered	0.975330	Binding	0.306	0.884	0.625											-4.007	Likely Benign	0.717	Likely Pathogenic	Likely Benign										0.130	Likely Benign	-1.15	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	3.96	Benign	0.01	Affected			0.2253	0.2651		0	-2	-5.3	44.01
c.2933C>A	P978Q 2D AIThe SynGAP1 missense variant P978Q is 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is 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		0.819762	Disordered	0.975775	Binding	0.425	0.892	0.625											-4.741	Likely Benign	0.305	Likely Benign	Likely Benign										0.091	Likely Benign	-1.72	Neutral	0.990	Probably Damaging	0.726	Possibly Damaging	4.15	Benign	0.01	Affected			0.1651	0.5699		0	-1	-1.9	31.01
c.2944T>A	Y982N 2D AIThe SynGAP1 Y982N 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is benign, and Foldetta results are unavailable. Overall, the majority of consensus‑based and high‑accuracy tools lean toward a benign interpretation. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar status, which currently has no entry for Y982N. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-4.536	Likely Benign	0.881	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-1.14	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	3.88	Benign	0.00	Affected			0.2090	0.0545		-2	-2	-2.2	-49.07
c.2944T>C	Y982H 2D AIThe SynGAP1 missense variant Y982H 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 the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus result is benign; Foldetta predictions are unavailable. Overall, the evidence is mixed, but the majority of consensus‑based and high‑accuracy tools lean toward a benign interpretation. Thus, the variant is most likely benign, 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 Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-2.675	Likely Benign	0.893	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-0.63	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	3.92	Benign	0.00	Affected			0.2352	0.0545		0	2	-1.9	-26.03
c.2944T>G	Y982D 2D AIThe SynGAP1 missense variant Y982D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-5.021	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-1.29	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	3.87	Benign	0.00	Affected			0.3959	0.0545		-4	-3	-2.2	-48.09
c.3058C>G	R1020G 2D AIThe SynGAP1 missense variant R1020G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500											-4.898	Likely Benign	0.868	Likely Pathogenic	Ambiguous										0.162	Likely Benign	-4.26	Deleterious	0.990	Probably Damaging	0.894	Possibly Damaging	2.48	Pathogenic	0.00	Affected			0.3394	0.3721		-3	-2	4.1	-99.14
c.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.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.3079A>T	N1027Y 2D AIThe SynGAP1 missense variant N1027Y 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 (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, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500											-5.799	Likely Benign	0.626	Likely Pathogenic	Likely Benign										0.074	Likely Benign	-2.15	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.70	Benign	0.03	Affected			0.0611	0.6133		-2	-2	2.2	49.07
c.3113C>T	T1038I 2D AIThe SynGAP1 T1038I missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Tools that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the balance of evidence leans toward a benign interpretation, with one high‑accuracy tool inconclusive and no conflicting ClinVar annotation. Thus, the variant is most likely benign, and there is no ClinVar status that contradicts this assessment. 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											-4.552	Likely Benign	0.877	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-2.02	Neutral	0.990	Probably Damaging	0.637	Possibly Damaging	2.69	Benign	0.04	Affected			0.1012	0.5036		0	-1	5.2	12.05
c.3154G>A	G1052R 2D AISynGAP1 missense variant G1052R is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign, and the SGM consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar uncertain status but provides additional support toward a likely benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875					Uncertain		1				-9.050	Likely Pathogenic	0.383	Ambiguous	Likely Benign										0.497	Likely Benign	-0.41	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	3.90	Benign	0.10	Tolerated	3.77	5	0.0976	0.4142		-2	-3	-4.1	99.14
c.3154G>C	G1052R 2D AIThe SynGAP1 missense variant G1052R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875											-9.050	Likely Pathogenic	0.383	Ambiguous	Likely Benign										0.497	Likely Benign	-0.41	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	3.90	Benign	0.10	Tolerated	3.77	5	0.0976	0.4142		-2	-3	-4.1	99.14
c.3218C>A	S1073Y 2D AIThe SynGAP1 missense change S1073Y 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750											-6.768	Likely Benign	0.752	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.43	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	3.81	Benign	0.00	Affected			0.0977	0.5684		-3	-2	-0.5	76.10
c.3218C>T	S1073F 2D AIThe SynGAP1 missense variant S1073F 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, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, 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 (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. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750											-6.783	Likely Benign	0.836	Likely Pathogenic	Ambiguous										0.161	Likely Benign	-2.58	Deleterious	0.990	Probably Damaging	0.796	Possibly Damaging	3.81	Benign	0.00	Affected			0.0952	0.5957		-3	-2	3.6	60.10
c.3260C>A	S1087Y 2D AIThe SynGAP1 missense variant S1087Y is catalogued in gnomAD (ID 6‑33443812‑C‑A) and has no ClinVar entry. 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 (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as benign, and no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.912647	Disordered	0.974805	Binding	0.357	0.891	1.000								6-33443812-C-A			-4.194	Likely Benign	0.587	Likely Pathogenic	Likely Benign										0.107	Likely Benign	-2.41	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.56	Benign	0.02	Affected	3.77	5	0.0671	0.5845		-2	-3	-0.5	76.10
c.3260C>T	S1087F 2D AISynGAP1 missense variant S1087F 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, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of reliable predictors and the two high‑accuracy tools suggest a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.912647	Disordered	0.974805	Binding	0.357	0.891	1.000					Uncertain		1				-3.843	Likely Benign	0.497	Ambiguous	Likely Benign										0.105	Likely Benign	-2.75	Deleterious	0.990	Probably Damaging	0.796	Possibly Damaging	2.56	Benign	0.03	Affected	3.77	5	0.0645	0.6029		-2	-3	3.6	60.10
c.3280T>C	S1094P 2D AIThe SynGAP1 missense variant S1094P is 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools 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 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 S1094P, 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		0.938133	Disordered	0.981352	Binding	0.358	0.877	1.000											-2.430	Likely Benign	0.285	Likely Benign	Likely Benign										0.124	Likely Benign	-1.31	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	2.46	Pathogenic	0.13	Tolerated			0.2322	0.6099		1	-1	-0.8	10.04
c.3281C>A	S1094Y 2D AIThe SynGAP1 missense variant S1094Y is not reported in ClinVar (status: none) but is present in gnomAD (ID 6‑33443833‑C‑A). 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 (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 predictions therefore show a benign call from AlphaMissense‑Optimized, an inconclusive SGM Consensus, and no Foldetta data. Overall, the balance of evidence leans toward a pathogenic interpretation (five pathogenic versus four benign calls), and this 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.			0.938133	Disordered	0.981352	Binding	0.358	0.877	1.000								6-33443833-C-A			-5.609	Likely Benign	0.631	Likely Pathogenic	Likely Benign										0.155	Likely Benign	-2.07	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.45	Pathogenic	0.02	Affected	3.77	5	0.1007	0.5877		-2	-3	-0.5	76.10
c.3281C>T	S1094F 2D AIThe SynGAP1 missense variant S1094F is not 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 agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of conventional predictors lean toward pathogenicity, but the single high‑accuracy tool predicts benign and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the 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.			0.938133	Disordered	0.981352	Binding	0.358	0.877	1.000											-5.655	Likely Benign	0.666	Likely Pathogenic	Likely Benign										0.150	Likely Benign	-2.17	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.45	Pathogenic	0.02	Affected			0.0925	0.5851		-3	-2	3.6	60.10
c.3295T>C	Y1099H 2D AIThe SynGAP1 missense variant Y1099H is reported in gnomAD (variant ID 6-33443847‑T‑C) 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 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 reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is 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 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		0.885302	Disordered	0.974267	Binding	0.400	0.862	1.000								6-33443847-T-C	1	6.49e-7	-3.620	Likely Benign	0.267	Likely Benign	Likely Benign										0.123	Likely Benign	-0.50	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.76	Benign	0.18	Tolerated	3.77	5	0.2453	0.0735		2	0	-1.9	-26.03
c.3321G>C	Q1107H 2D AIThe SynGAP1 missense variant Q1107H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect 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. 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		0.876521	Disordered	0.951017	Binding	0.393	0.880	0.875											-3.546	Likely Benign	0.260	Likely Benign	Likely Benign										0.136	Likely Benign	-2.58	Deleterious	0.990	Probably Damaging	0.796	Possibly Damaging	2.51	Benign	0.01	Affected			0.1514	0.4683		3	0	0.3	9.01
c.3321G>T	Q1107H 2D AIThe SynGAP1 missense variant Q1107H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect 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, SGM‑Consensus as Likely Benign, while 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 entry exists. 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											-3.546	Likely Benign	0.260	Likely Benign	Likely Benign										0.136	Likely Benign	-2.58	Deleterious	0.990	Probably Damaging	0.796	Possibly Damaging	2.51	Benign	0.01	Affected			0.1514	0.4683		3	0	0.3	9.01
c.3353G>T	S1118I 2D AIThe SynGAP1 missense variant S1118I 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is 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		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750											-5.710	Likely Benign	0.154	Likely Benign	Likely Benign										0.309	Likely Benign	-1.09	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	5.16	Benign	0.01	Affected			0.1486	0.4580		-1	-2	5.3	26.08
c.3389A>T	K1130M 2D AIThe SynGAP1 K1130M 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, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the balance of evidence leans toward a benign classification, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for K1130M. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.844	Likely Benign	0.858	Likely Pathogenic	Ambiguous										0.476	Likely Benign	-1.62	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	5.42	Benign	0.00	Affected			0.1703	0.4407		0	-1	5.8	3.02
c.3446C>A	P1149Q 2D AIThe SynGAP1 missense variant P1149Q 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 a benign prediction, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is 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		0.762850	Disordered	0.786938	Binding	0.424	0.837	0.625											-4.235	Likely Benign	0.305	Likely Benign	Likely Benign										0.136	Likely Benign	-1.48	Neutral	0.990	Probably Damaging	0.798	Possibly Damaging	2.67	Benign	0.01	Affected			0.1515	0.4580		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.345G>C	Q115H 2D AIThe SynGAP1 missense variant Q115H is 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. 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” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is 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 Q115H, 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		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750											-3.888	Likely Benign	0.277	Likely Benign	Likely Benign										0.156	Likely Benign	-0.99	Neutral	0.990	Probably Damaging	0.969	Probably Damaging	4.08	Benign	0.17	Tolerated			0.1248	0.3383		3	0	0.3	9.01
c.345G>T	Q115H 2D AIThe SynGAP1 missense variant Q115H 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, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods points to a benign classification for Q115H, 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		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750											-3.888	Likely Benign	0.277	Likely Benign	Likely Benign										0.156	Likely Benign	-0.99	Neutral	0.990	Probably Damaging	0.969	Probably Damaging	4.08	Benign	0.17	Tolerated			0.1248	0.3383		3	0	0.3	9.01
c.3745A>G	R1249G 2D AIThe SynGAP1 missense variant R1249G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain and SGM‑Consensus is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-7.405	In-Between	0.684	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-5.38	Deleterious	0.990	Probably Damaging	0.828	Possibly Damaging	1.70	Pathogenic	0.00	Affected			0.3087	0.2393		-3	-2	4.1	-99.14
c.3746G>C	R1249T 2D AIThe SynGAP1 missense variant R1249T is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The SGM‑Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence (10 pathogenic vs. 2 benign predictions) points to a pathogenic impact for R1249T. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-8.014	Likely Pathogenic	0.712	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-4.59	Deleterious	0.990	Probably Damaging	0.903	Possibly Damaging	1.71	Pathogenic	0.00	Affected			0.1646	0.2458		-1	-1	3.8	-55.08
c.3802C>A	L1268M 2D AIThe SynGAP1 missense variant L1268M is reported in gnomAD (ID 6‑33447850‑C‑A) and has no ClinVar entry. 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, 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; a Foldetta stability analysis is not available. Overall, the preponderance of evidence from multiple in silico predictors and consensus methods 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	Coiled-coil	0.458154	Structured	0.804315	Binding	0.859	0.629	0.000								6-33447850-C-A			-4.689	Likely Benign	0.140	Likely Benign	Likely Benign										0.062	Likely Benign	-0.07	Neutral	0.990	Probably Damaging	0.796	Possibly Damaging	2.67	Benign	0.08	Tolerated	3.77	5	0.0627	0.2297		2	4	-1.9	18.03
c.3803T>A	L1268Q 2D AIThe SynGAP1 missense variant L1268Q 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 the two PolyPhen‑2 implementations (HumDiv and HumVar) predict 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 reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also indicates benign. Foldetta results are not available, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign impact for this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.458154	Structured	0.804315	Binding	0.859	0.629	0.000											-5.707	Likely Benign	0.143	Likely Benign	Likely Benign										0.062	Likely Benign	-0.50	Neutral	0.990	Probably Damaging	0.637	Possibly Damaging	2.68	Benign	0.08	Tolerated			0.0988	0.0558		-2	-2	-7.3	14.97
c.3851T>A	L1284Q 2D AIThe SynGAP1 missense variant L1284Q is not 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 (two benign vs. two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta remain unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875											-4.730	Likely Benign	0.094	Likely Benign	Likely Benign										0.138	Likely Benign	-2.80	Deleterious	0.990	Probably Damaging	0.796	Possibly Damaging	2.48	Pathogenic	0.01	Affected			0.1065	0.0488		-2	-2	-7.3	14.97
c.3851T>C	L1284P 2D AIThe SynGAP1 missense variant L1284P is not reported in ClinVar (no ClinVar ID) but is present in gnomAD (ID 6‑33447899‑T‑C). 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‑to‑2 split. Foldetta results are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation (five pathogenic versus four benign predictions). This assessment does not conflict with ClinVar, as the variant has no ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875								6-33447899-T-C			-2.451	Likely Benign	0.076	Likely Benign	Likely Benign										0.191	Likely Benign	-3.05	Deleterious	0.990	Probably Damaging	0.722	Possibly Damaging	2.48	Pathogenic	0.01	Affected	3.77	5	0.3307	0.0848		-3	-3	-5.4	-16.04
c.3851T>G	L1284R 2D AIThe SynGAP1 missense variant L1284R is not 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). 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.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875											-4.203	Likely Benign	0.156	Likely Benign	Likely Benign										0.163	Likely Benign	-3.11	Deleterious	0.990	Probably Damaging	0.722	Possibly Damaging	2.48	Pathogenic	0.00	Affected			0.1216	0.0488		-3	-2	-8.3	43.03
c.3872T>A	L1291Q 2D AISynGAP1 missense variant L1291Q 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, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict pathogenicity are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is equivocal (two benign, two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence is split, with an equal number of benign and pathogenic calls and no decisive high‑accuracy consensus. Consequently, the variant’s likely effect remains uncertain; it is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.863458	Binding	0.579	0.797	0.625											-4.450	Likely Benign	0.207	Likely Benign	Likely Benign										0.290	Likely Benign	-4.18	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	2.49	Pathogenic	0.01	Affected			0.1052	0.1049		-2	-2	-7.3	14.97
c.3872T>C	L1291P 2D AIThe SynGAP1 missense variant L1291P is not 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 (two benign vs two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, five tools predict pathogenicity while four predict benignity, giving a slight tilt toward a pathogenic interpretation. Because there is no ClinVar assertion, this prediction does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.863458	Binding	0.579	0.797	0.625											-3.322	Likely Benign	0.243	Likely Benign	Likely Benign										0.417	Likely Benign	-4.32	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	2.48	Pathogenic	0.01	Affected			0.3078	0.2162		-3	-3	-5.4	-16.04
c.3872T>G	L1291R 2D AIThe SynGAP1 missense variant L1291R is not reported in ClinVar and is present in gnomAD (ID 6‑33447920‑T‑G). 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. High‑accuracy assessment shows AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and Foldetta results are unavailable. Overall, the majority of conventional predictors indicate a pathogenic effect, whereas the single high‑accuracy tool suggests benign. No ClinVar annotation contradicts these findings. Thus, based on the collective evidence, the variant is most likely pathogenic, though the high‑accuracy prediction introduces uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.863458	Binding	0.579	0.797	0.625								6-33447920-T-G	1	6.44e-7	-3.977	Likely Benign	0.302	Likely Benign	Likely Benign										0.287	Likely Benign	-4.29	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	2.49	Pathogenic	0.00	Affected	3.77	5	0.1160	0.1049		-2	-3	-8.3	43.03
c.3899C>A	P1300H 2D AIThe SynGAP1 missense variant P1300H 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 interpretation: 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 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		0.788093	Disordered	0.885826	Binding	0.400	0.834	0.875											-5.062	Likely Benign	0.140	Likely Benign	Likely Benign										0.093	Likely Benign	-1.48	Neutral	0.990	Probably Damaging	0.840	Possibly Damaging	2.80	Benign	0.01	Affected			0.1757	0.3802		0	-2	-1.6	40.02
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.3908G>T	G1303V 2D AIThe SynGAP1 missense variant G1303V is 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. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.886612	Binding	0.429	0.854	0.875											-3.513	Likely Benign	0.162	Likely Benign	Likely Benign										0.147	Likely Benign	-2.44	Neutral	0.990	Probably Damaging	0.846	Possibly Damaging	2.79	Benign	0.02	Affected			0.1511	0.3508		-1	-3	4.6	42.08
c.390A>C	Q130H 2D AIThe SynGAP1 missense variant Q130H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus also predicts likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment 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		0.509769	Disordered	0.718853	Binding	0.306	0.885	0.375											-3.828	Likely Benign	0.387	Ambiguous	Likely Benign										0.074	Likely Benign	-1.09	Neutral	0.990	Probably Damaging	0.969	Probably Damaging	4.10	Benign	0.01	Affected			0.1727	0.3970		3	0	0.3	9.01
c.390A>T	Q130H 2D AIThe SynGAP1 missense variant Q130H is not reported in ClinVar and has no entry in 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. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically highlight benign predictions: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the balance of evidence points to a benign effect for the variant, 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 Benign		0.509769	Disordered	0.718853	Binding	0.306	0.885	0.375											-3.828	Likely Benign	0.387	Ambiguous	Likely Benign										0.074	Likely Benign	-1.09	Neutral	0.990	Probably Damaging	0.969	Probably Damaging	4.10	Benign	0.01	Affected			0.1727	0.3970		3	0	0.3	9.01
c.460A>C	S154R 2D AIThe SynGAP1 missense variant S154R is not 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 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‑accuracy predictors (five pathogenic vs four benign) indicate a pathogenic impact. 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.			0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-9.119	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.097	Likely Benign	-1.73	Neutral	0.990	Probably Damaging	0.723	Possibly Damaging	4.10	Benign	0.14	Tolerated			0.0997	0.3298		0	-1	-3.7	69.11
c.461G>T	S154I 2D AIThe SynGAP1 missense variant S154I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not provided and is treated as unavailable. High‑accuracy predictions therefore indicate a benign outcome (AlphaMissense‑Optimized) with no decisive evidence from SGM Consensus or Foldetta. Overall, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-10.061	Likely Pathogenic	0.665	Likely Pathogenic	Likely Benign										0.105	Likely Benign	-2.24	Neutral	0.990	Probably Damaging	0.797	Possibly Damaging	4.03	Benign	0.07	Tolerated			0.0953	0.5123		-1	-2	5.3	26.08
c.462C>A	S154R 2D AIThe SynGAP1 missense variant S154R is not 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 (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, more tools (five) predict pathogenicity than benign (four), and the high‑accuracy AlphaMissense‑Optimized also indicates pathogenicity. Therefore, 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.			0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-9.119	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.072	Likely Benign	-1.73	Neutral	0.990	Probably Damaging	0.723	Possibly Damaging	4.10	Benign	0.14	Tolerated			0.0997	0.3298		0	-1	-3.7	69.11
c.462C>G	S154R 2D AIThe SynGAP1 missense variant S154R is not 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 (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, more tools (five) predict pathogenicity than benign (four), and the high‑accuracy AlphaMissense‑Optimized also indicates pathogenicity. Therefore, 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.			0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-9.119	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.072	Likely Benign	-1.73	Neutral	0.990	Probably Damaging	0.723	Possibly Damaging	4.10	Benign	0.14	Tolerated			0.0997	0.3298		0	-1	-3.7	69.11
c.550G>C	E184Q 2D AIThe SynGAP1 missense variant E184Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-11.927	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-2.55	Deleterious	0.990	Probably Damaging	0.815	Possibly Damaging	3.47	Benign	0.00	Affected			0.1688	0.7914		2	2	0.0	-0.98
c.577G>A	A193T 2D AIThe SynGAP1 missense variant A193T is 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 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 as Likely Benign; Foldetta results are not available. 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		0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-4.973	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.208	Likely Benign	-1.36	Neutral	0.990	Probably Damaging	0.815	Possibly Damaging	4.07	Benign	0.21	Tolerated			0.1452	0.7231		1	0	-2.5	30.03
c.577G>T	A193S 2D AIThe SynGAP1 missense variant A193S is 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 of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. 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		0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-2.408	Likely Benign	0.533	Ambiguous	Likely Benign										0.180	Likely Benign	-1.62	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	4.04	Benign	0.04	Affected			0.2595	0.5852		1	1	-2.6	16.00
c.578C>G	A193G 2D AIThe SynGAP1 missense variant A193G is not 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 and 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. 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.			0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-4.822	Likely Benign	0.835	Likely Pathogenic	Ambiguous										0.136	Likely Benign	-2.61	Deleterious	0.990	Probably Damaging	0.760	Possibly Damaging	4.00	Benign	0.01	Affected			0.2283	0.4999		1	0	-2.2	-14.03
c.583G>T	A195S 2D AIThe SynGAP1 missense variant A195S is listed in gnomAD (6‑33435225‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome 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 this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the four high‑accuracy predictors) 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 available predictions 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		0.346032	Structured	0.430388	Uncertain	0.363	0.533	0.125								6-33435225-G-T	1	6.20e-7	-4.936	Likely Benign	0.618	Likely Pathogenic	Likely Benign										0.078	Likely Benign	-1.13	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	4.10	Benign	0.08	Tolerated	3.54	6	0.1846	0.4427		1	1	-2.6	16.00
c.584C>G	A195G 2D AIThe SynGAP1 missense variant A195G 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, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools give uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that AlphaMissense‑Optimized remains uncertain, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—favors a pathogenic outcome. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A195G, 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.			0.346032	Structured	0.430388	Uncertain	0.363	0.533	0.125											-7.186	In-Between	0.907	Likely Pathogenic	Ambiguous										0.146	Likely Benign	-2.64	Deleterious	0.990	Probably Damaging	0.760	Possibly Damaging	4.01	Benign	0.05	Affected			0.1694	0.3388		1	0	-2.2	-14.03
c.592C>A	L198I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198I is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain or inconclusive results come from AlphaMissense‑Default, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-10.411	Likely Pathogenic	0.563	Ambiguous	Likely Benign	0.59	Ambiguous	0.1	0.70	Ambiguous	0.65	Ambiguous	0.10	Likely Benign	0.234	Likely Benign	-1.72	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	3.43	Benign	0.00	Affected			0.0921	0.3307		2	2	0.7	0.00
c.592C>G	L198V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L198V variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (3 pathogenic vs. 1 benign) indicates pathogenicity; Foldetta remains uncertain. Overall, the majority of evaluated tools predict a pathogenic impact, and this is not contradicted by any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-9.343	Likely Pathogenic	0.747	Likely Pathogenic	Likely Benign	1.10	Ambiguous	0.2	1.24	Ambiguous	1.17	Ambiguous	0.34	Likely Benign	0.265	Likely Benign	-2.54	Deleterious	0.990	Probably Damaging	0.675	Possibly Damaging	3.44	Benign	0.00	Affected			0.1520	0.3017		2	1	0.4	-14.03
c.598T>G	L200V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L200V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and the Foldetta stability assessment. Uncertain results come from Rosetta and premPS. 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 pathogenic. Overall, the majority of evidence points to a benign effect; 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	PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125											-6.917	Likely Benign	0.213	Likely Benign	Likely Benign	2.15	Destabilizing	0.2	1.85	Ambiguous	2.00	Destabilizing	0.92	Ambiguous	0.098	Likely Benign	-1.07	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	4.09	Benign	0.24	Tolerated			0.1593	0.3607		2	1	0.4	-14.03
c.608A>G	D203G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203G 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, premPS, ESM1b, FATHMM, AlphaMissense‑Optimized, and Foldetta. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools give uncertain results: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (two benign vs. one pathogenic, one uncertain); and Foldetta also predicts benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evidence supports a benign effect, and this is consistent with the lack of any ClinVar pathogenic classification. 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											-6.332	Likely Benign	0.350	Ambiguous	Likely Benign	0.07	Likely Benign	0.1	0.72	Ambiguous	0.40	Likely Benign	0.03	Likely Benign	0.231	Likely Benign	-3.42	Deleterious	0.990	Probably Damaging	0.681	Possibly Damaging	4.01	Benign	0.04	Affected			0.2708	0.4312		1	-1	3.1	-58.04
c.609T>A	D203E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203E 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 SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two PolyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta)—all uniformly classify the variant as benign. No prediction or folding‑stability result is missing or inconclusive. Based on the consensus of the majority of tools and the unanimous high‑accuracy predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-4.067	Likely Benign	0.201	Likely Benign	Likely Benign	0.10	Likely Benign	0.0	0.08	Likely Benign	0.09	Likely Benign	-0.07	Likely Benign	0.152	Likely Benign	-0.93	Neutral	0.990	Probably Damaging	0.675	Possibly Damaging	4.15	Benign	0.81	Tolerated			0.0975	0.4189		3	2	0.0	14.03
c.609T>G	D203E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203E 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 SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two PolyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta)—all uniformly classify the variant as benign. No prediction or folding‑stability result is missing or inconclusive. Based on the consensus of the majority of tools and the unanimous high‑accuracy predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-4.067	Likely Benign	0.201	Likely Benign	Likely Benign	0.10	Likely Benign	0.0	0.08	Likely Benign	0.09	Likely Benign	-0.07	Likely Benign	0.152	Likely Benign	-0.93	Neutral	0.990	Probably Damaging	0.675	Possibly Damaging	4.15	Benign	0.81	Tolerated			0.0975	0.4189		3	2	0.0	14.03
c.656G>A	C219Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219Y is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized returns a pathogenic prediction; 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 pathogenicity. Based on the preponderance of evidence, the variant is most likely pathogenic, a conclusion that does not contradict its ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000					Uncertain		1				-14.797	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	8.98	Destabilizing	2.0	2.84	Destabilizing	5.91	Destabilizing	0.55	Ambiguous	0.812	Likely Pathogenic	-9.09	Deleterious	0.990	Probably Damaging	0.758	Possibly Damaging	5.81	Benign	0.00	Affected			0.0772	0.3285		0	-2	-3.8	60.04
c.730G>A	E244K 2D AISynGAP1 missense variant E244K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from FoldX, Rosetta, Foldetta, SIFT, and FATHMM, whereas pathogenic predictions are reported by REVEL, PROVEAN, both polyPhen‑2 HumDiv and HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). The high‑accuracy methods give a clearer picture: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. With the majority of consensus tools leaning toward pathogenic and the two high‑accuracy pathogenic predictions outweighing the benign Foldetta result, the variant is most likely pathogenic. 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	PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-13.975	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	1.0	0.45	Likely Benign	0.43	Likely Benign	0.80	Ambiguous	0.841	Likely Pathogenic	-3.37	Deleterious	0.990	Probably Damaging	0.760	Possibly Damaging	5.82	Benign	0.07	Tolerated			0.1887	0.6177		0	1	-0.4	-0.94
c.730G>C	E244Q 2D AIThe SynGAP1 E244Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, six tools predict pathogenicity versus five predicting benignity, with no ClinVar evidence to contradict these findings. Thus, the variant is most likely pathogenic based on the current predictive landscape. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-10.245	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.9	-0.77	Ambiguous	-0.27	Likely Benign	0.40	Likely Benign	0.695	Likely Pathogenic	-2.49	Neutral	0.990	Probably Damaging	0.815	Possibly Damaging	5.78	Benign	0.05	Affected			0.1016	0.5610		2	2	0.0	-0.98
c.731A>G	E244G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of computational evidence points to the variant being most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-10.452	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.28	Ambiguous	0.0	0.74	Ambiguous	1.01	Ambiguous	1.01	Destabilizing	0.900	Likely Pathogenic	-5.67	Deleterious	0.990	Probably Damaging	0.815	Possibly Damaging	5.73	Benign	0.01	Affected			0.2266	0.5252		0	-2	3.1	-72.06
c.745G>A	A249T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A249T is listed in ClinVar (ID 1031675.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, and FATHMM, whereas polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. Predictions that are inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. Overall, the balance of evidence favors a benign interpretation, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.505461	Disordered	0.255452	Uncertain	0.810	0.336	0.125					Uncertain		1				-3.564	Likely Benign	0.805	Likely Pathogenic	Ambiguous	1.50	Ambiguous	0.6	1.39	Ambiguous	1.45	Ambiguous	0.30	Likely Benign	0.487	Likely Benign	-0.96	Neutral	0.990	Probably Damaging	0.815	Possibly Damaging	5.65	Benign	0.40	Tolerated	3.39	15	0.0909	0.4972		1	0	-2.5	30.03	214.5	-43.3	0.0	0.0	0.5	0.2						X		Potentially Benign	The methyl group of Ala249, located on the surface of an α helix (res. Ala236-Val250) facing an anti-parallel β sheet strand (res. Ile205-Val209), packs against nearby hydrophobic residues such as Leu200, Leu246, and Val250. In the variant simulations, the hydroxyl group of Thr249, which is not suitable for hydrophobic packing, forms a stable hydrogen bond with the backbone carbonyl of Asn245 in the same helix. Although this interaction could theoretically weaken the structural integrity of the α helix, this destabilizing effect is not observed in the variant simulations.
c.745G>T	A249S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A249S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome 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, is classified as Likely Benign. Protein‑stability assessments are mixed: FoldX indicates a benign effect, while Rosetta and Foldetta are uncertain. High‑accuracy predictions show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the preponderance of evidence—including the high‑accuracy tools—suggests that A249S 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	PH	0.505461	Disordered	0.255452	Uncertain	0.810	0.336	0.125											-5.707	Likely Benign	0.634	Likely Pathogenic	Likely Benign	0.48	Likely Benign	0.3	0.84	Ambiguous	0.66	Ambiguous	0.33	Likely Benign	0.465	Likely Benign	-1.40	Neutral	0.990	Probably Damaging	0.681	Possibly Damaging	5.63	Benign	0.19	Tolerated			0.1962	0.3393		1	1	-2.6	16.00
c.746C>G	A249G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A249G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Only FATHMM predicts a benign outcome. Uncertain results are reported by FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM‑Consensus as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence supports a pathogenic classification for A249G, and 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.	Likely Pathogenic	PH	0.505461	Disordered	0.255452	Uncertain	0.810	0.336	0.125											-9.678	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	1.04	Ambiguous	0.2	2.02	Destabilizing	1.53	Ambiguous	1.19	Destabilizing	0.607	Likely Pathogenic	-2.97	Deleterious	0.990	Probably Damaging	0.760	Possibly Damaging	5.59	Benign	0.04	Affected			0.1667	0.2675		1	0	-2.2	-14.03
c.746C>T	A249V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A249V missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include premPS, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy methods are likewise inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, no high‑accuracy tool provides a definitive pathogenic or benign verdict. Overall, the majority of available predictions (seven pathogenic vs. three benign) lean toward a pathogenic interpretation. 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.		PH	0.505461	Disordered	0.255452	Uncertain	0.810	0.336	0.125											-9.417	Likely Pathogenic	0.856	Likely Pathogenic	Ambiguous	1.48	Ambiguous	0.6	0.51	Ambiguous	1.00	Ambiguous	0.41	Likely Benign	0.652	Likely Pathogenic	-2.47	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	5.76	Benign	0.03	Affected			0.0737	0.4677		0	0	2.4	28.05
c.1016A>C	K339T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339T missense variant is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools are split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic calls are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further highlight this discordance: the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect, whereas Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign impact. AlphaMissense‑Optimized returned an uncertain result and is treated as unavailable. Overall, the majority of robust predictors lean toward pathogenicity, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-10.061	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.0	0.10	Likely Benign	0.21	Likely Benign	-0.04	Likely Benign	0.512	Likely Pathogenic	-4.73	Deleterious	0.991	Probably Damaging	0.795	Possibly Damaging	1.94	Pathogenic	0.10	Tolerated			0.1900	0.3020		0	-1	3.2	-27.07
c.1017G>C	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for K339N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1017G>T	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K339N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact for K339N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.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.1103C>A	P368Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P368Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Remaining tools (AlphaMissense‑Default, FoldX, Rosetta, Foldetta, premPS) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of definitive predictions (five pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.363090	Structured	0.439989	Uncertain	0.580	0.677	0.250											-6.019	Likely Benign	0.413	Ambiguous	Likely Benign	1.56	Ambiguous	0.8	1.71	Ambiguous	1.64	Ambiguous	0.71	Ambiguous	0.205	Likely Benign	-5.10	Deleterious	0.991	Probably Damaging	0.881	Possibly Damaging	1.71	Pathogenic	0.04	Affected			0.1694	0.5283		0	-1	-1.9	31.01
c.1103C>G	P368R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P368R missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is uncertain. Overall, the majority of evidence—including the SGM‑Consensus and several individual high‑accuracy tools—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	C2	0.363090	Structured	0.439989	Uncertain	0.580	0.677	0.250											-9.564	Likely Pathogenic	0.736	Likely Pathogenic	Likely Benign	1.57	Ambiguous	1.0	1.54	Ambiguous	1.56	Ambiguous	0.58	Ambiguous	0.263	Likely Benign	-6.07	Deleterious	0.991	Probably Damaging	0.881	Possibly Damaging	1.78	Pathogenic	0.00	Affected			0.1439	0.3922		0	-2	-2.9	59.07
c.1103C>T	P368L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P368L is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438008‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Predictions that are uncertain or inconclusive are FoldX, Rosetta, premPS, AlphaMissense‑Default, and Foldetta. High‑accuracy assessments give AlphaMissense‑Optimized a benign score, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Based on the overall distribution of predictions, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.363090	Structured	0.439989	Uncertain	0.580	0.677	0.250								6-33438008-C-T	1	6.33e-7	-6.520	Likely Benign	0.444	Ambiguous	Likely Benign	1.52	Ambiguous	0.7	1.15	Ambiguous	1.34	Ambiguous	0.52	Ambiguous	0.248	Likely Benign	-6.61	Deleterious	0.991	Probably Damaging	0.831	Possibly Damaging	1.77	Pathogenic	0.00	Affected	3.42	19	0.2336	0.7125		-3	-3	5.4	16.04
c.1177G>C	G393R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G393R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include Rosetta and premPS, whereas the remaining tools—SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. 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	0.538167	Disordered	0.402365	Uncertain	0.333	0.670	0.625											-9.148	Likely Pathogenic	0.815	Likely Pathogenic	Ambiguous	3.88	Destabilizing	1.4	-0.38	Likely Benign	1.75	Ambiguous	0.47	Likely Benign	0.596	Likely Pathogenic	-2.99	Deleterious	0.991	Probably Damaging	0.881	Possibly Damaging	1.32	Pathogenic	0.02	Affected			0.1353	0.4464		-3	-2	-4.1	99.14
c.1178G>A	G393D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G393D is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SIFT, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized reports a benign outcome, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable. Overall, the preponderance of evidence points to a pathogenic effect for G393D, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.538167	Disordered	0.402365	Uncertain	0.333	0.670	0.625											-5.247	Likely Benign	0.717	Likely Pathogenic	Likely Benign	3.30	Destabilizing	1.4	-1.00	Ambiguous	1.15	Ambiguous	0.57	Ambiguous	0.528	Likely Pathogenic	-2.60	Deleterious	0.991	Probably Damaging	0.831	Possibly Damaging	1.32	Pathogenic	0.19	Tolerated			0.2077	0.1645		1	-1	-3.1	58.04
c.1217A>C	Y406S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406S is not 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: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FoldX, Rosetta, premPS, and Foldetta all indicate pathogenicity. 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, 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 is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-12.014	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	3.51	Destabilizing	0.3	4.08	Destabilizing	3.80	Destabilizing	1.40	Destabilizing	0.190	Likely Benign	-6.72	Deleterious	0.991	Probably Damaging	0.886	Possibly Damaging	3.80	Benign	0.06	Tolerated			0.4719	0.2817		-3	-2	0.5	-76.10
c.1223C>G	T408R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T408R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The premPS score is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. With six benign versus seven pathogenic calls overall, the evidence is mixed, but the presence of two independent high‑accuracy benign predictions and the lack of ClinVar or gnomAD support suggests the variant is most likely benign, and this does not contradict any existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000											-12.075	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	-0.48	Likely Benign	0.1	-0.24	Likely Benign	-0.36	Likely Benign	0.79	Ambiguous	0.138	Likely Benign	-4.06	Deleterious	0.991	Probably Damaging	0.645	Possibly Damaging	4.12	Benign	0.15	Tolerated			0.1029	0.3180		-1	-1	-3.8	55.08
c.1333G>A	E445K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E445K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic calls arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. When high‑accuracy methods are considered separately, AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence—including the high‑accuracy tools—supports a pathogenic effect. This conclusion does not conflict with ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-15.371	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.02	Likely Benign	0.0	0.02	Likely Benign	0.02	Likely Benign	0.46	Likely Benign	0.524	Likely Pathogenic	-3.82	Deleterious	0.991	Probably Damaging	0.951	Probably Damaging	3.35	Benign	0.02	Affected			0.1784	0.5311		0	1	-0.4	-0.94
c.1379A>G	K460R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K460R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity, while Rosetta and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Taken together, the overwhelming majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-5.349	Likely Benign	0.175	Likely Benign	Likely Benign	-0.41	Likely Benign	0.0	0.63	Ambiguous	0.11	Likely Benign	0.55	Ambiguous	0.103	Likely Benign	-1.52	Neutral	0.991	Probably Damaging	0.962	Probably Damaging	3.46	Benign	0.63	Tolerated			0.5093	0.1169	Weaken	3	2	-0.6	28.01
c.1382C>G	A461G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461G has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into three groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; the remaining tools (FoldX, premPS, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, with no ClinVar record to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-11.360	Likely Pathogenic	0.556	Ambiguous	Likely Benign	1.46	Ambiguous	0.1	2.06	Destabilizing	1.76	Ambiguous	0.83	Ambiguous	0.276	Likely Benign	-3.79	Deleterious	0.991	Probably Damaging	0.628	Possibly Damaging	3.32	Benign	0.00	Affected			0.1988	0.3317		1	0	-2.2	-14.03
c.1528A>T	I510F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510F is 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 AlphaMissense‑Optimized, whereas the majority of tools (SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and Foldetta) predict a pathogenic impact; Rosetta remains uncertain. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Overall, the preponderance of evidence indicates that the variant 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	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000											-8.185	Likely Pathogenic	0.713	Likely Pathogenic	Likely Benign	4.66	Destabilizing	0.7	1.38	Ambiguous	3.02	Destabilizing	0.50	Likely Benign	0.692	Likely Pathogenic	-2.64	Deleterious	0.991	Probably Damaging	0.854	Possibly Damaging	-1.14	Pathogenic	0.01	Affected			0.0552	0.1794		1	0	-1.7	34.02
c.1619A>G	Q540R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540R has no ClinVar entry and is present in gnomAD (ID 6‑33438862‑A‑G). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Two tools report uncertainty: premPS and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points to a benign impact, with only a minority of tools indicating pathogenicity. This conclusion does not contradict ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000								6-33438862-A-G	1	6.19e-7	-13.312	Likely Pathogenic	0.540	Ambiguous	Likely Benign	-0.06	Likely Benign	0.0	-0.07	Likely Benign	-0.07	Likely Benign	0.88	Ambiguous	0.795	Likely Pathogenic	-3.98	Deleterious	0.991	Probably Damaging	0.985	Probably Damaging	-1.28	Pathogenic	0.08	Tolerated	3.37	35	0.1328	0.1886		1	1	-1.0	28.06
c.1648G>A	A550T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A550T missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SIFT, Rosetta, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. FoldX, Foldetta, and premPS are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta’s stability analysis is uncertain. Overall, the majority of reliable predictors (8/11) indicate a pathogenic impact, whereas only three suggest benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000											-10.555	Likely Pathogenic	0.621	Likely Pathogenic	Likely Benign	1.68	Ambiguous	0.3	-0.05	Likely Benign	0.82	Ambiguous	0.73	Ambiguous	0.627	Likely Pathogenic	-3.19	Deleterious	0.991	Probably Damaging	0.872	Possibly Damaging	-1.25	Pathogenic	0.10	Tolerated			0.0931	0.4465		1	0	-2.5	30.03
c.1674C>A	H558Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H558Q is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify the variant as benign include SIFT, FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Two tools report uncertainty: AlphaMissense‑Default and premPS. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. No prediction or folding stability result is missing. Overall, the majority of tools lean toward pathogenicity, but the presence of several benign predictions and conflicting high‑accuracy outputs suggests uncertainty. The variant is most likely pathogenic based on the prevailing evidence, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.033407	Structured	0.011039	Uncertain	0.897	0.200	0.000											-11.483	Likely Pathogenic	0.496	Ambiguous	Likely Benign	-0.26	Likely Benign	0.1	0.05	Likely Benign	-0.11	Likely Benign	0.97	Ambiguous	0.522	Likely Pathogenic	-4.23	Deleterious	0.991	Probably Damaging	0.702	Possibly Damaging	-1.25	Pathogenic	0.13	Tolerated			0.1182	0.2058		3	0	-0.3	-9.01
c.1674C>G	H558Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H558Q is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify the variant as benign include SIFT, FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Two tools report uncertainty: AlphaMissense‑Default and premPS. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. No prediction or folding stability result is missing. Overall, the majority of tools lean toward pathogenicity, but the presence of several benign predictions and conflicting high‑accuracy outputs suggests uncertainty. The variant is most likely pathogenic based on the prevailing evidence, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.033407	Structured	0.011039	Uncertain	0.897	0.200	0.000											-11.483	Likely Pathogenic	0.496	Ambiguous	Likely Benign	-0.26	Likely Benign	0.1	0.05	Likely Benign	-0.11	Likely Benign	0.97	Ambiguous	0.522	Likely Pathogenic	-4.23	Deleterious	0.991	Probably Damaging	0.702	Possibly Damaging	-1.25	Pathogenic	0.13	Tolerated			0.1182	0.2058		3	0	-0.3	-9.01
c.1836G>C	Q612H 2D AIThe SynGAP1 missense variant Q612H 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 Rosetta, which scores the variant as benign. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. FoldX and premPS are inconclusive, and Foldetta is unavailable for definitive interpretation. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000											-9.733	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.70	Ambiguous	0.9	0.39	Likely Benign	0.55	Ambiguous	0.79	Ambiguous	0.550	Likely Pathogenic	-4.55	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	-1.26	Pathogenic	0.02	Affected			0.1379	0.3084		3	0	0.3	9.01
c.1836G>T	Q612H 2D AIThe SynGAP1 missense variant Q612H 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 Rosetta, which scores the variant as benign. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. FoldX and premPS are inconclusive, and Foldetta is unavailable for definitive interpretation. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000											-9.733	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.70	Ambiguous	0.9	0.39	Likely Benign	0.55	Ambiguous	0.79	Ambiguous	0.550	Likely Pathogenic	-4.55	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	-1.26	Pathogenic	0.02	Affected			0.1379	0.3084		3	0	0.3	9.01
c.1906T>G	F636V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-14.603	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.1	5.13	Destabilizing	4.10	Destabilizing	1.07	Destabilizing	0.533	Likely Pathogenic	-6.74	Deleterious	0.991	Probably Damaging	0.985	Probably Damaging	3.44	Benign	0.04	Affected			0.1841	0.2030		-1	-1	1.4	-48.04
c.2006A>C	N669T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy methods give a split verdict: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts it to be pathogenic; Foldetta remains inconclusive. Overall, the majority of tools favor a pathogenic interpretation, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-9.875	Likely Pathogenic	0.565	Likely Pathogenic	Likely Benign	0.74	Ambiguous	0.1	0.68	Ambiguous	0.71	Ambiguous	0.49	Likely Benign	0.292	Likely Benign	-5.25	Deleterious	0.991	Probably Damaging	0.962	Probably Damaging	3.50	Benign	0.17	Tolerated			0.1504	0.4803		0	0	2.8	-13.00
c.2018T>G	L673R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L673R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote). FoldX and Foldetta are inconclusive. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM Consensus, and an uncertain outcome from Foldetta. Overall, the majority of evidence points toward pathogenicity, and this conclusion does not conflict with the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-14.474	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	1.10	Ambiguous	0.2	2.04	Destabilizing	1.57	Ambiguous	1.23	Destabilizing	0.178	Likely Benign	-3.81	Deleterious	0.991	Probably Damaging	0.433	Benign	3.36	Benign	0.03	Affected			0.1348	0.1015		-3	-2	-8.3	43.03
c.2024A>C	N675T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Uncertain results come from Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. No evidence contradicts the ClinVar status. Overall, the balance of evidence, especially from the high‑accuracy tools, indicates that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-10.636	Likely Pathogenic	0.208	Likely Benign	Likely Benign	0.36	Likely Benign	0.3	-0.67	Ambiguous	-0.16	Likely Benign	0.56	Ambiguous	0.258	Likely Benign	-4.63	Deleterious	0.991	Probably Damaging	0.710	Possibly Damaging	3.49	Benign	0.05	Affected			0.1283	0.7910		0	0	2.8	-13.00
c.2092G>A	E698K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a benign impact. Because the high‑accuracy predictions are split, the overall evidence is inconclusive, but the majority of tools lean toward pathogenicity. The variant is therefore most likely pathogenic based on the preponderance of predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-8.881	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.23	Likely Benign	0.1	0.38	Likely Benign	0.31	Likely Benign	-0.07	Likely Benign	0.466	Likely Benign	-3.79	Deleterious	0.991	Probably Damaging	0.951	Probably Damaging	3.37	Benign	0.01	Affected			0.2218	0.4383		0	1	-0.4	-0.94
c.2120C>G	A707G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) give uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of definitive predictions lean toward a benign effect, and there is no ClinVar status to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-7.480	In-Between	0.224	Likely Benign	Likely Benign	1.45	Ambiguous	0.0	1.52	Ambiguous	1.49	Ambiguous	0.62	Ambiguous	0.198	Likely Benign	-2.60	Deleterious	0.991	Probably Damaging	0.960	Probably Damaging	3.42	Benign	0.01	Affected			0.1678	0.2388		1	0	-2.2	-14.03
c.2120C>T	A707V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707V variant is not reported in ClinVar (no ClinVar ID) but is present in gnomAD (variant ID 6‑33441585‑C‑T). Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign classification. Only three tools—Rosetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar—predict pathogenicity, while Foldetta reports an uncertain stability change. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta remains uncertain. Overall, the majority of evidence supports a benign impact for A707V, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000								6-33441585-C-T	1	6.20e-7	-6.479	Likely Benign	0.277	Likely Benign	Likely Benign	0.05	Likely Benign	0.0	2.17	Destabilizing	1.11	Ambiguous	-0.30	Likely Benign	0.212	Likely Benign	-1.62	Neutral	0.991	Probably Damaging	0.912	Probably Damaging	3.45	Benign	1.00	Tolerated	3.50	9	0.0794	0.4048		0	0	2.4	28.05
c.2242C>A	L748M 2D AIThe SynGAP1 missense variant L748M 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. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this 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		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750											-3.935	Likely Benign	0.089	Likely Benign	Likely Benign										0.060	Likely Benign	-0.12	Neutral	0.991	Probably Damaging	0.852	Possibly Damaging	2.70	Benign	0.05	Affected			0.0909	0.3863		4	2	-1.9	18.03
c.232C>T	R78C 2D AIThe SynGAP1 missense variant R78C is 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 R78C, 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		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500											-6.079	Likely Benign	0.467	Ambiguous	Likely Benign										0.114	Likely Benign	-2.13	Neutral	0.991	Probably Damaging	0.194	Benign	3.80	Benign	0.00	Affected			0.3255	0.2804		-4	-3	7.0	-53.05
c.2330T>C	L777P 2D AIThe SynGAP1 missense variant L777P is catalogued in gnomAD (6‑33442488‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by 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 also indicates a likely benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for the variant, 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		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250								6-33442488-T-C			-5.807	Likely Benign	0.361	Ambiguous	Likely Benign										0.255	Likely Benign	-2.13	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.94	Benign	0.00	Affected	3.64	6	0.3732	0.1664		-3	-3	-5.4	-16.04
c.2330T>G	L777R 2D AIThe SynGAP1 missense variant L777R is 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. 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		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-6.084	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.227	Likely Benign	-2.20	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.97	Benign	0.00	Affected			0.1249	0.0846		-3	-2	-8.3	43.03
c.2332A>C	N778H 2D AIThe SynGAP1 missense variant N778H is 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, 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 this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-4.761	Likely Benign	0.172	Likely Benign	Likely Benign										0.100	Likely Benign	-1.62	Neutral	0.991	Probably Damaging	0.980	Probably Damaging	4.17	Benign	0.04	Affected			0.1400	0.7220		2	1	0.3	23.04
c.2332A>T	N778Y 2D AIThe SynGAP1 missense variant N778Y 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). AlphaMissense‑Default is uncertain, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500											-5.723	Likely Benign	0.421	Ambiguous	Likely Benign										0.175	Likely Benign	-2.48	Neutral	0.991	Probably Damaging	0.980	Probably Damaging	4.16	Benign	0.02	Affected			0.0589	0.6139		-2	-2	2.2	49.07
c.2333A>T	N778I 2D AIThe SynGAP1 missense variant N778I is reported in gnomAD (ID 6‑33442491‑A‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the four high‑accuracy predictors) 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 points to a benign impact, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500								6-33442491-A-T			-6.659	Likely Benign	0.622	Likely Pathogenic	Likely Benign										0.150	Likely Benign	-2.48	Neutral	0.991	Probably Damaging	0.980	Probably Damaging	4.17	Benign	0.02	Affected	3.64	6	0.0628	0.6128		-3	-2	8.0	-0.94
c.2431C>A	P811T 2D AIThe SynGAP1 missense variant P811T is 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 polyPhen‑2 (HumDiv and HumVar) and SIFT all predict 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 further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect for P811T, 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	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-5.329	Likely Benign	0.488	Ambiguous	Likely Benign										0.119	Likely Benign	-1.94	Neutral	0.991	Probably Damaging	0.864	Possibly Damaging	2.77	Benign	0.03	Affected			0.1679	0.6095		0	-1	0.9	3.99
c.2570G>A	S857N 2D AIThe SynGAP1 missense variant S857N 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 assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that 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		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-5.065	Likely Benign	0.137	Likely Benign	Likely Benign										0.128	Likely Benign	0.24	Neutral	0.991	Probably Damaging	0.982	Probably Damaging	4.09	Benign	1.00	Tolerated			0.1515	0.5034		1	1	-2.7	27.03
c.2576G>A	S859N 2D AIThe SynGAP1 missense variant S859N is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which contains no pathogenic classification. 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											-8.184	Likely Pathogenic	0.225	Likely Benign	Likely Benign										0.142	Likely Benign	-0.62	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	3.99	Benign	0.29	Tolerated			0.1221	0.5226		1	1	-2.7	27.03
c.2615C>T	S872L 2D AIThe SynGAP1 missense variant S872L 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, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus likewise favors a benign classification; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign effect for S872L, and this assessment does not conflict with ClinVar, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.662664	Binding	0.262	0.865	0.125											-6.450	Likely Benign	0.555	Ambiguous	Likely Benign										0.178	Likely Benign	-2.28	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	2.61	Benign	0.04	Affected			0.1168	0.5283		-3	-2	4.6	26.08
c.2618G>A	S873N 2D AIThe SynGAP1 missense variant S873N is 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S873N, 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		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-6.453	Likely Benign	0.706	Likely Pathogenic	Likely Benign										0.180	Likely Benign	-1.88	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.66	Benign	0.12	Tolerated			0.1440	0.4612		1	1	-2.7	27.03
c.2624C>T	A875V 2D AIThe SynGAP1 missense variant A875V 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 also 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		0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-4.946	Likely Benign	0.255	Likely Benign	Likely Benign										0.116	Likely Benign	-1.17	Neutral	0.991	Probably Damaging	0.904	Possibly Damaging	2.74	Benign	1.00	Tolerated			0.1099	0.6605		0	0	2.4	28.05
c.2684G>A	S895N 2D AIThe SynGAP1 missense variant S895N 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect 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, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote) also leans benign. No Foldetta (protein‑folding stability) result is available, so it does not influence the assessment. Overall, the preponderance of predictions indicates the variant is most likely benign, 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 Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750					Uncertain		1				-6.399	Likely Benign	0.604	Likely Pathogenic	Likely Benign										0.118	Likely Benign	-0.85	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.64	Benign	0.30	Tolerated	4.32	4	0.1271	0.4984		1	1	-2.7	27.03
c.2768T>A	I923N 2D AIThe SynGAP1 missense variant I923N (ClinVar ID 647043.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign” because the majority of its constituent tools (three benign, one pathogenic) favor a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as benign, and the Foldetta stability analysis is unavailable. Overall, the collective predictions point 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		0.562014	Disordered	0.964857	Binding	0.292	0.852	0.250					Uncertain		1				-0.733	Likely Benign	0.712	Likely Pathogenic	Likely Benign										0.108	Likely Benign	-1.16	Neutral	0.991	Probably Damaging	0.793	Possibly Damaging	2.70	Benign	0.13	Tolerated	3.77	5	0.1164	0.1073		-2	-3	-8.0	0.94
c.2948G>A	S983N 2D AISynGAP1 missense variant S983N is listed as Benign in ClinVar (ID 469153) and is present in gnomAD (6‑33443500‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, 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; Foldetta results are not available. Overall, the majority of available predictions (five pathogenic vs. three benign) suggest a pathogenic impact, which contradicts the ClinVar benign classification. 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					Likely Benign		1	6-33443500-G-A	6	3.72e-6	-5.604	Likely Benign	0.909	Likely Pathogenic	Ambiguous										0.136	Likely Benign	-1.78	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.04	Pathogenic	0.00	Affected	4.32	1	0.1933	0.4069		1	1	-2.7	27.03
c.2954G>A	S985N 2D AIThe SynGAP1 missense variant S985N is listed in ClinVar (ID 2087879.0) with an “Uncertain” status 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 effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. Separately, the high‑accuracy AlphaMissense‑Optimized result is “Uncertain,” and the Foldetta protein‑folding stability assessment is unavailable. Based on the overall distribution of predictions, the variant is most likely benign; this conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750					Uncertain		1				-6.979	Likely Benign	0.845	Likely Pathogenic	Ambiguous										0.088	Likely Benign	-1.68	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.65	Benign	0.00	Affected	4.32	1	0.1812	0.4822		1	1	-2.7	27.03
c.2996C>G	S999C 2D AIThe SynGAP1 missense variant S999C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and 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 S999C, 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		0.834292	Disordered	0.950682	Binding	0.262	0.897	0.625											-7.751	In-Between	0.139	Likely Benign	Likely Benign										0.049	Likely Benign	-1.68	Neutral	0.991	Probably Damaging	0.873	Possibly Damaging	2.63	Benign	0.01	Affected			0.1131	0.6212		0	-1	3.3	16.06
c.3068C>T	S1023L 2D AIThe SynGAP1 missense variant S1023L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the balance of evidence from the majority of tools and the SGM‑Consensus indicates a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.831250	Disordered	0.990262	Binding	0.322	0.750	0.500											-5.735	Likely Benign	0.705	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-3.47	Deleterious	0.991	Probably Damaging	0.991	Probably Damaging	2.47	Pathogenic	0.01	Affected			0.1080	0.4923		-3	-2	4.6	26.08
c.3263G>A	S1088N 2D AIThe SynGAP1 missense variant S1088N has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, while the SGM‑Consensus (derived from the four high‑accuracy tools) indicates 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 balance of evidence leans toward a benign impact, 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 Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-5.227	Likely Benign	0.791	Likely Pathogenic	Ambiguous										0.155	Likely Benign	-1.25	Neutral	0.991	Probably Damaging	0.982	Probably Damaging	2.69	Benign	0.02	Affected			0.1940	0.5197		1	1	-2.7	27.03
c.3487C>A	H1163N 2D AIThe SynGAP1 missense variant H1163N is 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. 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 (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 for H1163N, 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		0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375											-3.219	Likely Benign	0.643	Likely Pathogenic	Likely Benign										0.280	Likely Benign	-1.70	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	5.47	Benign	0.17	Tolerated			0.1588	0.2759		2	1	-0.3	-23.04
c.3487C>G	H1163D 2D AISynGAP1 missense variant H1163D 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, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized rates the variant as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie and is therefore unavailable, and Foldetta folding‑stability analysis is not provided. With an equal number of benign and pathogenic predictions and no decisive high‑accuracy evidence, the variant remains ambiguous. Thus, it is most likely neither clearly benign nor pathogenic, and this uncertainty aligns with its ClinVar status of uncertain significance. 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					Uncertain		1				-2.107	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.476	Likely Benign	-2.60	Deleterious	0.991	Probably Damaging	0.991	Probably Damaging	5.44	Benign	0.31	Tolerated	3.88	3	0.2145	0.1986		1	-1	-0.3	-22.05
c.3487C>T	H1163Y 2D AIThe SynGAP1 missense variant H1163Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is 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 based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375											-4.051	Likely Benign	0.688	Likely Pathogenic	Likely Benign										0.390	Likely Benign	-1.81	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	5.40	Benign	0.08	Tolerated			0.0845	0.4487		0	2	1.9	26.03
c.3488A>G	H1163R 2D AIThe SynGAP1 missense variant H1163R is 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 SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and no Foldetta stability data is available. Overall, the majority of evidence points to a benign impact. 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 Benign		0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375											-2.505	Likely Benign	0.942	Likely Pathogenic	Ambiguous										0.472	Likely Benign	-2.08	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.43	Benign	0.27	Tolerated			0.1863	0.2402		2	0	-1.3	19.05
c.3551C>T	S1184L 2D AIThe SynGAP1 missense variant S1184L 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 polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the balance of evidence from high‑accuracy tools leans toward a benign classification, and this assessment does not contradict any ClinVar status, as none exists for S1184L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.648219	Disordered	0.514669	Binding	0.624	0.642	0.500											-2.595	Likely Benign	0.939	Likely Pathogenic	Ambiguous										0.156	Likely Benign	-1.87	Neutral	0.991	Probably Damaging	0.987	Probably Damaging	2.75	Benign	0.06	Tolerated			0.0822	0.4577		-3	-2	4.6	26.08
c.3569G>A	S1190N 2D AIThe SynGAP1 missense variant S1190N is catalogued in gnomAD (6‑33444604‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Benign,” and Foldetta results are unavailable. Overall, the balance of evidence favors a benign effect for S1190N, and this conclusion is not contradicted by any ClinVar status (none reported). 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								6-33444604-G-A	2	1.24e-6	-4.909	Likely Benign	0.811	Likely Pathogenic	Ambiguous										0.326	Likely Benign	-1.25	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	5.27	Benign	0.07	Tolerated	3.82	4	0.1368	0.3441		1	1	-2.7	27.03
c.3580A>G	R1194G 2D AIThe SynGAP1 missense variant R1194G is 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, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of conventional tools lean toward pathogenicity, and the high‑accuracy predictions are split, with no ClinVar evidence to contradict the pathogenic interpretation. 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.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-6.849	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.477	Likely Benign	-2.17	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.56	Benign	0.02	Affected			0.3275	0.2847		-3	-2	4.1	-99.14
c.3581G>C	R1194T 2D AIThe SynGAP1 missense variant R1194T 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, ESM1b, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are split, with four tools supporting benign and four supporting pathogenic, and the high‑accuracy consensus is conflicting. Based on the available 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	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-4.875	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.402	Likely Benign	-1.96	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.50	Benign	0.02	Affected			0.1866	0.3706		-1	-1	3.8	-55.08
c.3582G>C	R1194S 2D AIThe SynGAP1 missense variant R1194S is not reported in ClinVar and is absent from gnomAD. Prediction tools show a split assessment: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy analyses highlight AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta data are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, with a minority of tools and the consensus suggesting benignity. This prediction does not contradict ClinVar status, as no ClinVar entry exists for R1194S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-5.139	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.362	Likely Benign	-1.60	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.57	Benign	0.02	Affected			0.3284	0.3281		0	-1	3.7	-69.11
c.3582G>T	R1194S 2D AIThe SynGAP1 missense variant R1194S is not reported in ClinVar and is absent from gnomAD. Prediction tools show a split assessment: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy analyses highlight AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta data are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, with a minority of tools and the consensus suggesting benignity. This prediction does not contradict ClinVar status, as no ClinVar entry exists for R1194S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-5.139	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.362	Likely Benign	-1.60	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.57	Benign	0.02	Affected			0.3284	0.3281		0	-1	3.7	-69.11
c.3725A>T	E1242V 2D AIThe E1242V missense change occurs in the coiled‑coil domain of SynGAP1. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized. Those that predict a pathogenic outcome include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (which is “Likely Pathogenic”). ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which simply lacks an entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.557691	Disordered	0.456349	Uncertain	0.870	0.549	0.500											-7.456	In-Between	0.691	Likely Pathogenic	Likely Benign										0.267	Likely Benign	-5.46	Deleterious	0.991	Probably Damaging	0.898	Possibly Damaging	2.17	Pathogenic	0.00	Affected			0.0447	0.4320		-2	-2	7.7	-29.98
c.3729G>C	Q1243H 2D AIThe SynGAP1 missense variant Q1243H is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6-33446721‑G‑C). 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 conclusion 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	Coiled-coil	0.545602	Disordered	0.433693	Uncertain	0.887	0.551	0.500								6-33446721-G-C	1	6.19e-7	-5.281	Likely Benign	0.204	Likely Benign	Likely Benign										0.107	Likely Benign	-1.90	Neutral	0.991	Probably Damaging	0.897	Possibly Damaging	2.65	Benign	0.02	Affected	3.77	5	0.0943	0.1813		0	3	0.3	9.01
c.3729G>T	Q1243H 2D AIThe SynGAP1 missense variant Q1243H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: 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 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, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.545602	Disordered	0.433693	Uncertain	0.887	0.551	0.500											-5.281	Likely Benign	0.204	Likely Benign	Likely Benign										0.107	Likely Benign	-1.90	Neutral	0.991	Probably Damaging	0.897	Possibly Damaging	2.65	Benign	0.02	Affected	3.77	5	0.0943	0.1813		0	3	0.3	9.01
c.3848C>A	P1283Q 2D AIThe SynGAP1 missense variant P1283Q is reported in gnomAD (variant ID 6‑33447896‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence indicates that the variant is most likely benign, 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		0.762850	Disordered	0.819686	Binding	0.484	0.732	0.875								6-33447896-C-A			-4.028	Likely Benign	0.085	Likely Benign	Likely Benign										0.102	Likely Benign	-1.11	Neutral	0.991	Probably Damaging	0.567	Possibly Damaging	2.72	Benign	0.04	Affected	3.77	5	0.1195	0.2926		-1	0	-1.9	31.01
c.3862A>C	K1288Q 2D AIThe SynGAP1 missense variant K1288Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL, 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, yields a 2‑to‑2 split and is therefore inconclusive. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence is divided, with an equal number of benign and pathogenic calls, leaving the variant’s clinical significance uncertain. This uncertainty does not contradict ClinVar, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-2.369	Likely Benign	0.172	Likely Benign	Likely Benign										0.173	Likely Benign	-2.51	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.4149	0.0657		1	1	0.4	-0.04
c.3863A>C	K1288T 2D AIThe SynGAP1 missense variant K1288T is not 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 and 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 results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy consensus also leans pathogenic. Therefore, 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.			0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-2.616	Likely Benign	0.477	Ambiguous	Likely Benign										0.227	Likely Benign	-4.84	Deleterious	0.991	Probably Damaging	0.982	Probably Damaging	2.09	Pathogenic	0.00	Affected			0.2066	0.2614		0	-1	3.2	-27.07
c.3864G>C	K1288N 2D AIThe SynGAP1 missense variant K1288N has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no result for this variant. High‑accuracy assessments therefore show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3864G>T	K1288N 2D AIThe SynGAP1 missense variant K1288N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy assessments therefore show an uncertain AlphaMissense‑Optimized prediction, a Likely Pathogenic SGM‑Consensus, and no Foldetta data. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3885G>C	Q1295H 2D AIThe SynGAP1 missense variant Q1295H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625											-4.851	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.349	Likely Benign	-4.08	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.1345	0.3203		3	0	0.3	9.01
c.3885G>T	Q1295H 2D AIThe SynGAP1 missense variant Q1295H is catalogued in gnomAD (ID 6‑33447933‑G‑T) but has no ClinVar submission. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. When predictions are grouped, 3 tools predict benign and 6 predict pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this substitution. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625								6-33447933-G-T			-4.851	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.349	Likely Benign	-4.08	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.1345	0.3203		3	0	0.3	9.01
c.3934G>A	A1312T 2D AISynGAP1 missense variant A1312T 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 interpretation: 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. Overall, the majority of evidence points to a benign effect, 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		0.767246	Disordered	0.971112	Binding	0.392	0.902	0.750											-4.137	Likely Benign	0.083	Likely Benign	Likely Benign										0.155	Likely Benign	-0.65	Neutral	0.991	Probably Damaging	0.989	Probably Damaging	3.17	Benign	0.00	Affected			0.1865	0.7600		1	0	-2.5	30.03
c.3935C>T	A1312V 2D AIThe SynGAP1 missense variant A1312V is reported in gnomAD (ID 6‑33451809‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: six methods (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all predict a benign effect, while three tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT) predict pathogenicity. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns “Benign” and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability data are available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is listed). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.767246	Disordered	0.971112	Binding	0.392	0.902	0.750								6-33451809-C-T	4	2.48e-6	-4.585	Likely Benign	0.109	Likely Benign	Likely Benign										0.231	Likely Benign	-1.74	Neutral	0.991	Probably Damaging	0.983	Probably Damaging	3.15	Benign	0.00	Affected	3.77	5	0.1495	0.6343		0	0	2.4	28.05
c.566C>T	P189L 2D AIThe SynGAP1 missense variant P189L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic classification, with no ClinVar record to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250											-10.132	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-7.28	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	4.04	Benign	0.17	Tolerated			0.2283	0.7378		-3	-3	5.4	16.04
c.608A>T	D203V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools and the SGM Consensus lean toward a pathogenic interpretation, whereas two high‑accuracy methods (AlphaMissense‑Optimized and Foldetta) suggest benign. Because ClinVar contains no entry for this variant, there is no contradiction between the predictions and existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-10.660	Likely Pathogenic	0.523	Ambiguous	Likely Benign	0.32	Likely Benign	0.0	0.44	Likely Benign	0.38	Likely Benign	0.05	Likely Benign	0.289	Likely Benign	-4.07	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	3.98	Benign	0.02	Affected			0.0534	0.4084		-2	-3	7.7	-15.96
c.755C>T	P252L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P252L missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign are premPS and FATHMM, while the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic effect. Predictions from FoldX, Rosetta, and Foldetta are uncertain and therefore do not contribute to the overall assessment. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-10.181	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.93	Ambiguous	0.0	1.56	Ambiguous	1.25	Ambiguous	0.47	Likely Benign	0.794	Likely Pathogenic	-9.19	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	5.81	Benign	0.00	Affected			0.2027	0.6475		-3	-3	5.4	16.04
c.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.892C>T	P298S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P298S is listed in ClinVar as Benign (ClinVar ID 2965590.0) and is present in gnomAD (ID 6‑33437797‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. No evidence from FoldX, Rosetta, or premPS is available to support either outcome. Overall, the majority of predictions support a benign impact, aligning with the ClinVar designation. Thus, the variant is most likely benign and does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500					Benign		1	6-33437797-C-T	5	3.10e-6	-6.342	Likely Benign	0.144	Likely Benign	Likely Benign	1.38	Ambiguous	0.2	1.41	Ambiguous	1.40	Ambiguous	0.58	Ambiguous	0.189	Likely Benign	-1.20	Neutral	0.991	Probably Damaging	0.898	Possibly Damaging	2.03	Pathogenic	0.85	Tolerated	3.39	20	0.3678	0.5855		-1	1	0.8	-10.04
c.1123G>T	G375W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G375W is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438028‑G‑T). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence, including the high‑accuracy tools, points to a pathogenic effect for G375W. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.604312	Disordered	0.428340	Uncertain	0.301	0.836	0.625								6-33438028-G-T			-9.654	Likely Pathogenic	0.464	Ambiguous	Likely Benign	4.33	Destabilizing	2.0	7.01	Destabilizing	5.67	Destabilizing	0.22	Likely Benign	0.450	Likely Benign	-1.26	Neutral	0.992	Probably Damaging	0.869	Possibly Damaging	1.31	Pathogenic	0.01	Affected	4.32	12	0.0992	0.4368		-2	-7	-0.5	129.16
c.125C>A	P42H 2D AIThe SynGAP1 missense variant P42H 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 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		0.308712	Structured	0.431487	Uncertain	0.420	0.771	0.375											-3.088	Likely Benign	0.167	Likely Benign	Likely Benign										0.140	Likely Benign	-1.95	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	4.16	Benign	0.00	Affected			0.1995	0.3705		0	-2	-1.6	40.02
c.1306G>C	E436Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436Q is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include premPS and FATHMM, while the majority of tools predict a pathogenic outcome: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results 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 as uncertain. Overall, the consensus of pathogenic predictions outweighs benign ones, and the high‑accuracy tools reinforce a pathogenic classification. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.413	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	1.58	Ambiguous	1.05	Ambiguous	0.50	Likely Benign	0.607	Likely Pathogenic	-2.76	Deleterious	0.992	Probably Damaging	0.946	Probably Damaging	4.64	Benign	0.01	Affected			0.1237	0.5809		2	2	0.0	-0.98
c.1321G>T	V441F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V441F missense variant is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools lean toward a benign interpretation, and the high‑accuracy predictions are split but favor benign. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000											-13.519	Likely Pathogenic	0.653	Likely Pathogenic	Likely Benign	-0.26	Likely Benign	0.0	0.32	Likely Benign	0.03	Likely Benign	0.54	Ambiguous	0.355	Likely Benign	-4.22	Deleterious	0.992	Probably Damaging	0.658	Possibly Damaging	3.37	Benign	0.08	Tolerated			0.0670	0.3269		-1	-1	-1.4	48.04
c.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.1336G>C	E446Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E446Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability predictions are available. Overall, the balance of evidence from the consensus of multiple in silico predictors points to a pathogenic classification for E446Q. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000											-11.107	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign	0.92	Ambiguous	0.5	0.54	Ambiguous	0.73	Ambiguous	0.84	Ambiguous	0.337	Likely Benign	-2.80	Deleterious	0.992	Probably Damaging	0.973	Probably Damaging	3.24	Benign	0.04	Affected			0.1049	0.6218		2	2	0.0	-0.98
c.137C>A	P46H 2D AIThe SynGAP1 missense variant P46H is evaluated by multiple in silico tools. Consensus from SGM‑Consensus indicates a likely benign effect, and the variant is not reported in ClinVar or gnomAD. Functional predictors that agree on a benign outcome include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Predictors that flag a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports likely benign, while Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for P46H, and this conclusion is not contradicted by any ClinVar annotation. The variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.390993	Structured	0.433588	Uncertain	0.549	0.741	0.375											-4.022	Likely Benign	0.428	Ambiguous	Likely Benign										0.097	Likely Benign	-0.43	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	4.10	Benign	0.00	Affected			0.2360	0.5229		0	-2	-1.6	40.02
c.1420G>A	D474N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474N missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further indicate that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. AlphaMissense‑Optimized is inconclusive and therefore not considered evidence. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-10.696	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous	0.13	Likely Benign	0.0	0.31	Likely Benign	0.22	Likely Benign	0.06	Likely Benign	0.542	Likely Pathogenic	-4.21	Deleterious	0.992	Probably Damaging	0.990	Probably Damaging	-1.18	Pathogenic	0.08	Tolerated			0.1047	0.4135		2	1	0.0	-0.98
c.1520A>G	K507R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K507R is not listed in ClinVar (ClinVar status: not reported) but is present in gnomAD (gnomAD ID 6-33438552-A-G). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The high‑accuracy AlphaMissense‑Optimized score is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no pathogenic annotation for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000								6-33438552-A-G	1	6.20e-7	-7.363	In-Between	0.085	Likely Benign	Likely Benign	-0.08	Likely Benign	0.1	0.38	Likely Benign	0.15	Likely Benign	0.36	Likely Benign	0.503	Likely Pathogenic	-0.68	Neutral	0.992	Probably Damaging	0.980	Probably Damaging	-1.48	Pathogenic	0.27	Tolerated	3.37	35	0.3155	0.0579		2	3	-0.6	28.01
c.1561G>C	E521Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta predicts a benign stability change. Overall, the majority of evidence (9 benign vs. 4 pathogenic predictions) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-8.310	Likely Pathogenic	0.777	Likely Pathogenic	Likely Benign	-0.28	Likely Benign	0.2	0.19	Likely Benign	-0.05	Likely Benign	-0.06	Likely Benign	0.262	Likely Benign	-2.15	Neutral	0.992	Probably Damaging	0.993	Probably Damaging	3.30	Benign	0.11	Tolerated			0.1580	0.6552		2	2	0.0	-0.98
c.1564G>C	E522Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E522Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools show a split: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods reinforce this pattern: AlphaMissense‑Optimized classifies the change as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also labels it likely pathogenic, while Foldetta predicts a benign effect on protein stability. Overall, the majority of evidence points to a pathogenic impact. This assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-10.861	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	-0.13	Likely Benign	0.1	-0.06	Likely Benign	-0.10	Likely Benign	0.03	Likely Benign	0.560	Likely Pathogenic	-2.85	Deleterious	0.992	Probably Damaging	0.993	Probably Damaging	-1.33	Pathogenic	0.07	Tolerated			0.0944	0.4130		2	2	0.0	-0.98
c.1579G>A	D527N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527N 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 FoldX, Rosetta, Foldetta, and premPS, whereas a majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The high‑accuracy consensus methods give mixed results: AlphaMissense‑Optimized is uncertain, SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign outcome. Overall, the preponderance of evidence points toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-12.645	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.31	Likely Benign	1.0	0.09	Likely Benign	0.20	Likely Benign	0.22	Likely Benign	0.730	Likely Pathogenic	-4.87	Deleterious	0.992	Probably Damaging	0.990	Probably Damaging	-2.13	Pathogenic	0.01	Affected			0.0910	0.3754		2	1	0.0	-0.98
c.1744G>C	E582Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E582Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments—AlphaMissense‑Optimized, SGM‑Consensus, and Foldetta—all predict a benign impact, with Foldetta combining FoldX‑MD and Rosetta stability outputs. In contrast, the two polyPhen‑2 scores and AlphaMissense‑Default suggest pathogenicity, but these are outnumbered by benign predictions. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates that 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	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-3.700	Likely Benign	0.605	Likely Pathogenic	Likely Benign	0.17	Likely Benign	0.1	0.21	Likely Benign	0.19	Likely Benign	-0.24	Likely Benign	0.138	Likely Benign	-0.61	Neutral	0.992	Probably Damaging	0.993	Probably Damaging	3.22	Benign	0.57	Tolerated			0.0979	0.3402		2	2	0.0	-0.98
c.1756G>A	D586N 2D AIThe SynGAP1 D586N missense variant is not reported in ClinVar and has no gnomAD entry. Consensus prediction tools that agree on benign impact include FoldX, Rosetta, Foldetta, premPS, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, more tools predict pathogenicity than benign, and the high‑accuracy consensus leans toward pathogenic. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-9.497	Likely Pathogenic	0.767	Likely Pathogenic	Likely Benign	0.09	Likely Benign	0.8	0.24	Likely Benign	0.17	Likely Benign	0.19	Likely Benign	0.523	Likely Pathogenic	-2.52	Deleterious	0.992	Probably Damaging	0.995	Probably Damaging	-1.25	Pathogenic	0.23	Tolerated			0.1124	0.5253		2	1	0.0	-0.98
c.1819C>A	L607I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while benign calls are made by PROVEAN and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Stability predictions from FoldX, Rosetta, and premPS are inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for L607I. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-12.061	Likely Pathogenic	0.644	Likely Pathogenic	Likely Benign	0.63	Ambiguous	0.1	1.25	Ambiguous	0.94	Ambiguous	0.82	Ambiguous	0.727	Likely Pathogenic	-1.99	Neutral	0.992	Probably Damaging	0.997	Probably Damaging	-1.54	Pathogenic	0.01	Affected			0.1079	0.3767		2	2	0.7	0.00
c.1828C>A	L610I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610I is listed in gnomAD (ID 6‑33440880‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM. Four tools are uncertain (FoldX, Foldetta, premPS, AlphaMissense‑Default). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, whereas Foldetta’s stability estimate is unavailable. Overall, the balance of evidence points to a benign effect for L610I, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-A	1	6.19e-7	-6.362	Likely Benign	0.389	Ambiguous	Likely Benign	1.50	Ambiguous	0.2	0.18	Likely Benign	0.84	Ambiguous	0.76	Ambiguous	0.544	Likely Pathogenic	-1.86	Neutral	0.992	Probably Damaging	0.997	Probably Damaging	-1.34	Pathogenic	0.15	Tolerated	3.37	35	0.0999	0.3219		2	2	0.7	0.00
c.1915T>G	F639V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F639V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining 12 tools (SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity; Rosetta is uncertain and is therefore not counted. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-12.910	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	4.17	Destabilizing	0.1	1.18	Ambiguous	2.68	Destabilizing	1.47	Destabilizing	0.560	Likely Pathogenic	-6.97	Deleterious	0.992	Probably Damaging	0.756	Possibly Damaging	3.08	Benign	0.02	Affected			0.2074	0.1583		-1	-1	1.4	-48.04
c.197C>A	P66H 2D AIThe SynGAP1 missense variant P66H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, 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 result is benign; Foldetta predictions are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-4.134	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.239	Likely Benign	-2.26	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	3.89	Benign	0.00	Affected			0.1914	0.4675		0	-2	-1.6	40.02
c.1996G>A	E666K 2D AIThe SynGAP1 missense variant E666K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-11.367	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.20	Likely Benign	0.6	0.30	Likely Benign	0.25	Likely Benign	0.43	Likely Benign	0.401	Likely Benign	-3.26	Deleterious	0.992	Probably Damaging	0.717	Possibly Damaging	3.46	Benign	0.05	Affected			0.2953	0.5300		0	1	-0.4	-0.94
c.1997A>C	E666A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: FoldX (Uncertain) and AlphaMissense‑Optimized (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive because FoldX is Uncertain while Rosetta is Benign. Overall, the majority of available predictions (six pathogenic vs. five benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-11.122	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.1	0.18	Likely Benign	0.38	Likely Benign	0.50	Likely Benign	0.407	Likely Benign	-5.15	Deleterious	0.992	Probably Damaging	0.863	Possibly Damaging	3.45	Benign	0.07	Tolerated			0.3950	0.4878		0	-1	5.3	-58.04
c.1998G>C	E666D 2D 3DClick to see structure in 3D Viewer AISynGAP1 E666D is listed in ClinVar with an uncertain significance (ID 587483.0) and is not reported in gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and Rosetta; pathogenic calls come from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as likely pathogenic. High‑accuracy assessments give AlphaMissense‑Optimized a benign prediction, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the balance of evidence slightly favors a pathogenic interpretation, but the predictions are not unequivocal. Thus, the variant is most likely pathogenic according to the current computational data, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000					Uncertain		1				-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.1998G>T	E666D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666D missense variant is not reported in ClinVar (ClinVar ID: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. FoldX alone is also uncertain, so these results are treated as unavailable. Overall, the balance of evidence leans toward a pathogenic impact for E666D, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.2086C>G	L696V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696V variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) report a pathogenic outcome; Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for the variant, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000					Uncertain		1				-11.909	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	2.35	Destabilizing	0.1	1.85	Ambiguous	2.10	Destabilizing	1.46	Destabilizing	0.351	Likely Benign	-2.79	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected	3.46	13	0.1307	0.2830		1	2	0.4	-14.03
c.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.2131C>G	L711V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L711V is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441596‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000					Uncertain		1	6-33441596-C-G	1	6.20e-7	-10.045	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	3.48	Destabilizing	0.1	2.22	Destabilizing	2.85	Destabilizing	1.40	Destabilizing	0.170	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.34	Benign	0.00	Affected	3.50	9	0.1318	0.3010		1	2	0.4	-14.03
c.2224C>T	R742W 2D AIThe SynGAP1 missense variant R742W is listed in ClinVar (ID 2581888.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33441689‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. 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 benign impact, which is consistent with the ClinVar “Uncertain” classification and does not contradict it. 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					Uncertain		1	6-33441689-C-T	6	3.72e-6	-7.725	In-Between	0.133	Likely Benign	Likely Benign										0.079	Likely Benign	-1.71	Neutral	0.992	Probably Damaging	0.684	Possibly Damaging	2.66	Benign	0.01	Affected	4.32	2	0.1638	0.2839		-3	2	3.6	30.03
c.227C>G	S76C 2D AIThe SynGAP1 missense variant S76C is listed in ClinVar with an “Uncertain” status (ClinVar ID 1951273.0) and is present in the gnomAD database (gnomAD ID 6‑33425835‑C‑G). 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, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as benign; Foldetta results are not available for this variant. Overall, the majority of computational evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.444487	Uncertain	0.279	0.826	0.500					Uncertain		1	6-33425835-C-G	2	1.24e-6	-5.408	Likely Benign	0.100	Likely Benign	Likely Benign										0.076	Likely Benign	-1.78	Neutral	0.992	Probably Damaging	0.869	Possibly Damaging	3.71	Benign	0.00	Affected	4.32	1	0.0807	0.4787		0	-1	3.3	16.06
c.2281C>G	R761G 2D AIThe SynGAP1 missense variant R761G is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score it as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default tool remains 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, with no contradictory Foldetta data. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation; there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250											-4.453	Likely Benign	0.427	Ambiguous	Likely Benign										0.220	Likely Benign	-2.07	Neutral	0.992	Probably Damaging	0.900	Possibly Damaging	2.70	Benign	0.83	Tolerated			0.3333	0.3217		-3	-2	4.1	-99.14
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.2290A>G	N764D 2D AIThe SynGAP1 missense variant N764D is not 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, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. 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, SGM‑Consensus also predicts benign, and 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		0.380708	Structured	0.919527	Binding	0.305	0.861	0.250											-6.012	Likely Benign	0.572	Likely Pathogenic	Likely Benign										0.057	Likely Benign	-1.00	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	2.85	Benign	0.07	Tolerated			0.1769	0.2921		2	1	0.0	0.98
c.2291A>G	N764S 2D AIThe SynGAP1 missense variant N764S is listed in ClinVar as Benign (ClinVar ID 1948460.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, consistent with the ClinVar classification, and there is no contradiction between the predictions and the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.919527	Binding	0.305	0.861	0.250					Benign		1				-3.149	Likely Benign	0.159	Likely Benign	Likely Benign										0.058	Likely Benign	-0.84	Neutral	0.992	Probably Damaging	0.846	Possibly Damaging	2.65	Benign	0.61	Tolerated	3.64	6	0.3762	0.5062		1	1	2.7	-27.03
c.2292C>A	N764K 2D AIThe SynGAP1 missense variant N764K is not reported in ClinVar and has no entries 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 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 balance of evidence leans toward a benign classification, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.919527	Binding	0.305	0.861	0.250											-5.867	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.073	Likely Benign	-1.36	Neutral	0.992	Probably Damaging	0.921	Probably Damaging	2.66	Benign	0.02	Affected			0.2005	0.3539		1	0	-0.4	14.07
c.2292C>G	N764K 2D AIThe SynGAP1 missense variant N764K is not reported in ClinVar and has no entries 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 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 balance of evidence leans toward a benign classification, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.919527	Binding	0.305	0.861	0.250											-5.867	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.073	Likely Benign	-1.36	Neutral	0.992	Probably Damaging	0.921	Probably Damaging	2.66	Benign	0.02	Affected			0.2005	0.3539		1	0	-0.4	14.07
c.2327G>C	G776A 2D AIThe SynGAP1 missense variant G776A 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 for G776A, 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		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250											-5.275	Likely Benign	0.296	Likely Benign	Likely Benign										0.173	Likely Benign	-1.82	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	4.26	Benign	0.03	Affected			0.3648	0.4971		1	0	2.2	14.03
c.2335A>T	S779C 2D AIThe SynGAP1 missense variant S779C is 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. 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 for this variant. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-6.375	Likely Benign	0.196	Likely Benign	Likely Benign										0.230	Likely Benign	-1.88	Neutral	0.992	Probably Damaging	0.905	Possibly Damaging	2.28	Pathogenic	0.05	Affected			0.1177	0.6350		0	-1	3.3	16.06
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.2401G>T	G801C 2D AIThe SynGAP1 missense variant G801C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change 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 high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a benign outcome; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.874069	Disordered	0.636323	Binding	0.320	0.892	0.625											-7.542	In-Between	0.125	Likely Benign	Likely Benign										0.156	Likely Benign	-1.83	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	2.67	Benign	0.06	Tolerated			0.1039	0.4021		-3	-3	2.9	46.09
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.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.2468G>C	S823T 2D AIThe SynGAP1 missense variant S823T is not 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 agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two benign, two pathogenic). AlphaMissense‑Optimized predicts benign, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic effect, and this assessment does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.036	Likely Benign	0.717	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.02	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.05	Pathogenic	0.00	Affected			0.1453	0.6580		1	1	0.1	14.03
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.2471G>C	S824T 2D AIThe SynGAP1 missense variant S824T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default 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 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 (none is available). 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											-4.135	Likely Benign	0.500	Ambiguous	Likely Benign										0.116	Likely Benign	-0.74	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.62	Benign	0.47	Tolerated			0.1760	0.6525		1	1	0.1	14.03
c.2473T>A	S825T 2D AIThe SynGAP1 missense variant S825T is not 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 high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two benign, two pathogenic). AlphaMissense‑Optimized, a high‑accuracy model, 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 standard tools (5 pathogenic vs. 4 benign) suggest a pathogenic impact, while the single high‑accuracy model indicates benign. Thus, the variant is most likely pathogenic based on the collective predictions, 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.			0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-4.659	Likely Benign	0.615	Likely Pathogenic	Likely Benign										0.155	Likely Benign	-2.26	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.07	Pathogenic	0.05	Affected			0.1432	0.6658		1	1	0.1	14.03
c.2473T>G	S825A 2D AIThe SynGAP1 missense variant S825A is not reported in ClinVar (no entry) and is absent from gnomAD. Prediction tools that agree on benign include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on pathogenic are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates 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, has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic effect, while the high‑accuracy AlphaMissense‑Optimized suggests benign and the consensus is neutral. Given the preponderance of pathogenic predictions and the lack of conflicting evidence from ClinVar or population databases, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-4.878	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.135	Likely Benign	-2.30	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.04	Pathogenic	0.05	Affected			0.4794	0.5749		1	1	2.6	-16.00
c.2509G>A	V837I 2D AIThe SynGAP1 missense variant V837I is reported in ClinVar as “Not submitted” and is present in gnomAD (variant ID 6-33443061‑G‑A). 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 (HumDiv and HumVar) predict it to be pathogenic. When predictions are grouped by consensus, the benign group contains seven tools, while the pathogenic group contains two. High‑accuracy assessments reinforce the benign view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely benign. Foldetta results are unavailable. Overall, the majority of evidence indicates that V837I is most likely benign, and this conclusion 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		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125								6-33443061-G-A	1	6.19e-7	-4.299	Likely Benign	0.119	Likely Benign	Likely Benign										0.119	Likely Benign	-0.51	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.63	Benign	0.13	Tolerated	3.77	5	0.0833	0.3848		3	4	0.3	14.03
c.2509G>C	V837L 2D AIThe SynGAP1 missense variant V837L is 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 also indicates Likely Benign. Foldetta results are not available for this variant. 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		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125											-4.895	Likely Benign	0.313	Likely Benign	Likely Benign										0.118	Likely Benign	-1.15	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.64	Benign	0.17	Tolerated			0.1039	0.4623		2	1	-0.4	14.03
c.2510T>C	V837A 2D AIThe SynGAP1 missense variant V837A is 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 AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (majority vote of 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 (none is available). 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											-1.400	Likely Benign	0.370	Ambiguous	Likely Benign										0.073	Likely Benign	-0.41	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.70	Benign	1.00	Tolerated			0.3058	0.2106		0	0	-2.4	-28.05
c.2521G>C	V841L 2D AIThe SynGAP1 missense variant V841L is not 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-7.924	In-Between	0.514	Ambiguous	Likely Benign										0.157	Likely Benign	-0.01	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.85	Benign	0.56	Tolerated			0.0850	0.4233		2	1	-0.4	14.03
c.2521G>T	V841L 2D AIThe SynGAP1 missense variant V841L is not 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta results are unavailable. Overall, the balance of evidence favors a benign classification, 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.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-7.924	In-Between	0.514	Ambiguous	Likely Benign										0.157	Likely Benign	-0.01	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.85	Benign	0.56	Tolerated			0.0850	0.4233		2	1	-0.4	14.03
c.2522T>C	V841A 2D AIThe SynGAP1 missense variant V841A (ClinVar ID 1395978.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443074‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool reports an uncertain outcome, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie (two pathogenic, two benign) and is therefore inconclusive. No Foldetta stability assessment is available for this variant. Overall, the balance of evidence favors a pathogenic interpretation, which does not contradict the current ClinVar designation of Uncertain. 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					Uncertain		1	6-33443074-T-C	3	1.86e-6	-8.152	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.183	Likely Benign	-2.13	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.57	Benign	0.02	Affected	3.77	5	0.3069	0.2106		0	0	-2.4	-28.05
c.2535C>A	D845E 2D AIThe SynGAP1 missense variant D845E is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta stability analysis is unavailable. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. Overall, the balance of evidence points to a pathogenic effect for D845E, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.979	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-2.67	Deleterious	0.992	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1404	0.6998		3	2	0.0	14.03
c.2535C>G	D845E 2D AIThe SynGAP1 missense variant D845E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect for D845E, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.979	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-2.67	Deleterious	0.992	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1404	0.6998		3	2	0.0	14.03
c.2554G>T	G852C 2D AIThe SynGAP1 missense variant G852C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and Foldetta results are unavailable. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” and AlphaMissense‑Optimized independently predicts a benign outcome. With the majority of evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.506063	Binding	0.276	0.816	0.625											-7.462	In-Between	0.107	Likely Benign	Likely Benign										0.132	Likely Benign	-1.75	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	4.10	Benign	0.01	Affected			0.1278	0.4808		-3	-3	2.9	46.09
c.2557G>T	G853C 2D AIThe SynGAP1 G853C missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625											-7.021	In-Between	0.096	Likely Benign	Likely Benign										0.120	Likely Benign	-1.65	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	4.10	Benign	0.00	Affected			0.1292	0.4944		-3	-3	2.9	46.09
c.2624C>A	A875D 2D AIThe SynGAP1 missense variant A875D is not 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 data are unavailable. Overall, the majority of standard tools (5 pathogenic vs 4 benign) lean toward a pathogenic interpretation, but the high‑accuracy predictions are mixed or missing. 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.			0.545602	Disordered	0.632173	Binding	0.273	0.872	0.250											-3.268	Likely Benign	0.645	Likely Pathogenic	Likely Benign										0.149	Likely Benign	-2.78	Deleterious	0.992	Probably Damaging	0.913	Probably Damaging	2.68	Benign	0.02	Affected			0.1648	0.2035		0	-2	-5.3	44.01
c.2692T>A	S898T 2D AIThe SynGAP1 missense variant S898T 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. 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. 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		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500											-4.910	Likely Benign	0.166	Likely Benign	Likely Benign										0.097	Likely Benign	-0.33	Neutral	0.992	Probably Damaging	0.814	Possibly Damaging	2.50	Benign	0.78	Tolerated			0.1833	0.6209		1	1	0.1	14.03
c.2720G>C	S907T 2D AIThe SynGAP1 missense variant S907T is 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. The only tools that predict a pathogenic outcome 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. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250											-4.794	Likely Benign	0.220	Likely Benign	Likely Benign										0.178	Likely Benign	-0.53	Neutral	0.992	Probably Damaging	0.846	Possibly Damaging	2.66	Benign	0.93	Tolerated			0.1324	0.6352		1	1	0.1	14.03
c.2765G>A	R922Q 2D AIThe SynGAP1 missense variant R922Q is listed in ClinVar as Benign (ClinVar ID 2917638.0) and is present in gnomAD (ID 6‑33443317‑G‑A). 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, and PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (derived from the same set of high‑confidence predictors) also as 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, aligning with the ClinVar classification and indicating no contradiction. 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					Benign		1	6-33443317-G-A	7	4.34e-6	-3.295	Likely Benign	0.189	Likely Benign	Likely Benign										0.085	Likely Benign	-0.27	Neutral	0.992	Probably Damaging	0.736	Possibly Damaging	2.57	Benign	0.20	Tolerated	3.77	5	0.3444	0.2602		1	1	1.0	-28.06
c.2776T>A	S926T 2D AIThe SynGAP1 missense variant S926T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) is inconclusive, with two pathogenic and two benign votes. AlphaMissense‑Optimized, a high‑accuracy model, predicts benign, while Foldetta stability analysis is unavailable. Overall, the majority of standard tools favor a pathogenic effect, whereas the single high‑accuracy model suggests benign. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-2.917	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-2.34	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.55	Pathogenic	0.00	Affected			0.1174	0.5663		1	1	0.1	14.03
c.2776T>G	S926A 2D AIThe SynGAP1 missense variant S926A is not 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, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of reliable predictions indicate 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.			0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-3.042	Likely Benign	0.463	Ambiguous	Likely Benign										0.186	Likely Benign	-2.13	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.4657	0.4488		1	1	2.6	-16.00
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>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.2846G>T	G949V 2D AIThe SynGAP1 missense variant G949V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988861	Disordered	0.874971	Binding	0.365	0.923	0.750											-7.364	In-Between	0.102	Likely Benign	Likely Benign										0.328	Likely Benign	-0.55	Neutral	0.992	Probably Damaging	0.834	Possibly Damaging	2.21	Pathogenic	0.01	Affected			0.1493	0.3165		-1	-3	4.6	42.08
c.2902G>T	G968C 2D AIThe SynGAP1 missense variant G968C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, 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		0.978316	Disordered	0.961360	Binding	0.327	0.896	0.750											-8.441	Likely Pathogenic	0.117	Likely Benign	Likely Benign										0.170	Likely Benign	-0.99	Neutral	0.992	Probably Damaging	0.820	Possibly Damaging	4.12	Benign	0.07	Tolerated			0.1294	0.4768		-3	-3	2.9	46.09
c.2960A>T	D987V 2D AIThe SynGAP1 missense variant D987V is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence indicates that D987V is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750											-4.647	Likely Benign	0.857	Likely Pathogenic	Ambiguous										0.389	Likely Benign	-4.01	Deleterious	0.992	Probably Damaging	0.913	Probably Damaging	2.34	Pathogenic	0.00	Affected			0.0907	0.7202		-2	-3	7.7	-15.96
c.3007A>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.3008G>C	S1003T 2D AIThe SynGAP1 missense variant S1003T 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 majority of pathogenic predictors—polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT—suggest a damaging impact. The AlphaMissense‑Default score is uncertain, and Foldetta stability analysis is unavailable. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments therefore lean toward a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and no Foldetta data is present. Overall, the computational evidence supports a benign classification, 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 Benign		0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-5.140	Likely Benign	0.493	Ambiguous	Likely Benign										0.115	Likely Benign	-1.04	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.51	Benign	0.00	Affected			0.1864	0.6227		1	1	0.1	14.03
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.3014G>C	S1005T 2D AIThe SynGAP1 missense variant S1005T is 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 that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus 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 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	0.936602	Binding	0.261	0.897	0.750											-6.015	Likely Benign	0.454	Ambiguous	Likely Benign										0.120	Likely Benign	-1.30	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.66	Benign	0.00	Affected			0.1600	0.4937		1	1	0.1	14.03
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.3020G>C	S1007T 2D AIThe SynGAP1 missense variant S1007T is reported in ClinVar as “Not submitted” (no ClinVar entry) and is present in gnomAD (allele ID 6‑33443572‑G‑C). 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, classifies 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 overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is provided). 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								6-33443572-G-C			-4.719	Likely Benign	0.303	Likely Benign	Likely Benign										0.071	Likely Benign	-1.24	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.68	Benign	0.03	Affected	3.77	5	0.1796	0.5550		1	1	0.1	14.03
c.3098C>G	S1033C 2D AIThe SynGAP1 missense variant S1033C 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 S1033C, 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		0.910643	Disordered	0.993473	Binding	0.294	0.737	0.625											-6.263	Likely Benign	0.198	Likely Benign	Likely Benign										0.044	Likely Benign	-0.39	Neutral	0.992	Probably Damaging	0.750	Possibly Damaging	2.68	Benign	0.12	Tolerated			0.1031	0.5704		0	-1	3.3	16.06
c.3197C>G	P1066R 2D AIThe SynGAP1 missense variant P1066R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign interpretation: 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 for this variant. 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		0.967676	Disordered	0.968838	Binding	0.403	0.913	0.875											-5.154	Likely Benign	0.292	Likely Benign	Likely Benign										0.176	Likely Benign	-2.89	Deleterious	0.992	Probably Damaging	0.873	Possibly Damaging	2.63	Benign	0.00	Affected			0.1523	0.4742		0	-2	-2.9	59.07
c.3266G>A	G1089E 2D AIThe SynGAP1 missense variant G1089E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a 2‑vs‑2 split, and 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 for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000											-3.233	Likely Benign	0.926	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.85	Deleterious	0.992	Probably Damaging	0.834	Possibly Damaging	2.59	Benign	0.01	Affected			0.1460	0.4387		0	-2	-3.1	72.06
c.3298G>C	G1100R 2D AIThe SynGAP1 missense variant G1100R is not 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 assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions lean toward pathogenicity, and this does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875											-2.923	Likely Benign	0.603	Likely Pathogenic	Likely Benign										0.176	Likely Benign	-2.05	Neutral	0.992	Probably Damaging	0.906	Possibly Damaging	1.92	Pathogenic	0.00	Affected			0.0986	0.5217		-3	-2	-4.1	99.14
c.3299G>T	G1100V 2D AIThe SynGAP1 missense variant G1100V is reported in gnomAD (variant ID 6‑33443851‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign); pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments further support a benign outcome: 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. Overall, the balance of evidence favors a benign classification for G1100V, 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		0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875								6-33443851-G-T	1	6.51e-7	-2.362	Likely Benign	0.118	Likely Benign	Likely Benign										0.198	Likely Benign	-2.43	Neutral	0.992	Probably Damaging	0.906	Possibly Damaging	1.93	Pathogenic	0.01	Affected	3.77	5	0.1297	0.4036		-3	-1	4.6	42.08
c.3322A>T	S1108C 2D AIThe SynGAP1 missense variant S1108C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) support a pathogenic classification, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.949221	Binding	0.324	0.886	0.875											-9.189	Likely Pathogenic	0.183	Likely Benign	Likely Benign										0.118	Likely Benign	-3.30	Deleterious	0.992	Probably Damaging	0.820	Possibly Damaging	2.42	Pathogenic	0.04	Affected			0.0992	0.5299		0	-1	3.3	16.06
c.341A>T	K114M 2D AIThe SynGAP1 missense variant K114M is not reported in ClinVar and has no entry 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 the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points toward a benign effect, and there is no ClinVar entry to contradict this conclusion. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.953	Likely Benign	0.877	Likely Pathogenic	Ambiguous										0.120	Likely Benign	-1.89	Neutral	0.992	Probably Damaging	0.615	Possibly Damaging	3.90	Benign	0.00	Affected			0.1809	0.4075		0	-1	5.8	3.02
c.3425C>G	S1142C 2D AIThe SynGAP1 missense variant S1142C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign, and Foldetta data are unavailable. Consequently, the variant is most likely benign based on the collective evidence, and this conclusion does not conflict with 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.			0.919029	Disordered	0.719935	Binding	0.276	0.844	1.000											-7.355	In-Between	0.182	Likely Benign	Likely Benign										0.146	Likely Benign	-2.89	Deleterious	0.992	Probably Damaging	0.866	Possibly Damaging	2.70	Benign	0.00	Affected			0.1170	0.6016		0	-1	3.3	16.06
c.3437C>T	P1146L 2D AISynGAP1 missense variant P1146L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas a separate group predicts pathogenicity: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. AlphaMissense‑Default remains 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 favors a benign outcome, while Foldetta results are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, but the most accurate tools lean benign. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.732173	Binding	0.415	0.837	1.000											-2.182	Likely Benign	0.483	Ambiguous	Likely Benign										0.564	Likely Pathogenic	-5.25	Deleterious	0.992	Probably Damaging	0.912	Probably Damaging	5.51	Benign	0.00	Affected			0.2151	0.6446		-3	-3	5.4	16.04
c.3456G>C	E1152D 2D AIThe SynGAP1 missense variant E1152D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and 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 Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to the variant being most likely benign, 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		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-3.488	Likely Benign	0.669	Likely Pathogenic	Likely Benign										0.171	Likely Benign	-0.45	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.76	Benign	0.51	Tolerated			0.2151	0.4770		3	2	0.0	-14.03
c.3456G>T	E1152D 2D AIThe SynGAP1 missense variant E1152D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the 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 (majority vote) 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 the variant being most likely benign, 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		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-3.488	Likely Benign	0.669	Likely Pathogenic	Likely Benign										0.171	Likely Benign	-0.45	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.76	Benign	0.51	Tolerated			0.2151	0.4770		3	2	0.0	-14.03
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.3463G>C	V1155L 2D AIThe SynGAP1 missense variant V1155L is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in silico predictors shows a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar) and both AlphaMissense models. When predictions are grouped by agreement, the benign set includes five tools and the pathogenic set includes four. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence, especially from the high‑accuracy AlphaMissense‑Optimized and the SGM‑Consensus, suggests the variant is most likely benign, 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		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-2.823	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.229	Likely Benign	-1.26	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.63	Benign	0.09	Tolerated			0.0951	0.4175		2	1	-0.4	14.03
c.3463G>T	V1155L 2D AIThe SynGAP1 missense variant V1155L is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in silico predictors shows a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar) and both AlphaMissense models. When predictions are grouped by agreement, the benign set includes five tools and the pathogenic set includes four. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence, especially from the high‑accuracy AlphaMissense‑Optimized and the SGM‑Consensus, suggests the variant is most likely benign, 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		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-2.823	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.229	Likely Benign	-1.26	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.63	Benign	0.09	Tolerated			0.0951	0.4175		2	1	-0.4	14.03
c.3464T>C	V1155A 2D AIThe SynGAP1 missense variant V1155A is 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 polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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 balance of evidence leans toward 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		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-2.019	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.224	Likely Benign	0.77	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	3.15	Benign	1.00	Tolerated			0.3070	0.1859		0	0	-2.4	-28.05
c.3472G>A	V1158I 2D AIThe SynGAP1 missense variant V1158I is not 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 as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact, 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.			0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-3.504	Likely Benign	0.597	Likely Pathogenic	Likely Benign										0.129	Likely Benign	-0.20	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.49	Pathogenic	0.07	Tolerated			0.0863	0.4180		4	3	0.3	14.03
c.3472G>C	V1158L 2D AIThe SynGAP1 missense variant V1158L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Benign; Foldetta results are unavailable. Overall, the majority of evidence (five benign versus four pathogenic predictions, plus a benign consensus) points to a benign classification, and this does not contradict any ClinVar status because no ClinVar claim exists. Thus, the variant is most likely benign, though the AlphaMissense‑Optimized prediction introduces some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-2.345	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.187	Likely Benign	-0.73	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.78	Benign	0.56	Tolerated			0.1066	0.4642		2	1	-0.4	14.03
c.3473T>C	V1158A 2D AIThe SynGAP1 missense variant V1158A is not 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. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, 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 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.			0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-2.726	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.232	Likely Benign	-2.46	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.34	Pathogenic	0.02	Affected			0.2789	0.2906		0	0	-2.4	-28.05
c.349A>T	S117C 2D AIThe SynGAP1 missense variant S117C 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, 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 show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is 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		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-5.980	Likely Benign	0.201	Likely Benign	Likely Benign										0.246	Likely Benign	-1.81	Neutral	0.992	Probably Damaging	0.667	Possibly Damaging	3.68	Benign	0.00	Affected			0.1222	0.5057		0	-1	3.3	16.06
c.3503T>C	I1168T 2D AIThe SynGAP1 missense variant I1168T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. Overall, the high‑accuracy consensus (SGM‑Consensus) points to a benign outcome, whereas AlphaMissense‑Optimized remains inconclusive. Thus, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.763262	Binding	0.423	0.796	0.500											-2.970	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.426	Likely Benign	-1.29	Neutral	0.992	Probably Damaging	0.933	Probably Damaging	5.54	Benign	0.04	Affected			0.1173	0.1647		0	-1	-5.2	-12.05
c.3509G>A	S1170N 2D AIThe SynGAP1 missense variant S1170N is reported in gnomAD (6‑33444544‑G‑A) 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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. AlphaMissense‑Default is uncertain, and no Foldetta stability assessment is available. High‑accuracy predictions from AlphaMissense‑Optimized and the SGM‑Consensus both indicate a benign outcome, while the absence of a Foldetta result leaves that aspect unresolved. Overall, the majority of evidence points to a benign effect for S1170N, and this conclusion is not contradicted by any ClinVar classification (none is present). 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								6-33444544-G-A	1	6.20e-7	-3.705	Likely Benign	0.413	Ambiguous	Likely Benign										0.342	Likely Benign	-0.18	Neutral	0.992	Probably Damaging	0.925	Probably Damaging	5.39	Benign	0.86	Tolerated	4.32	4	0.1132	0.4238		1	1	-2.7	27.03
c.3509G>C	S1170T 2D AIThe SynGAP1 missense variant S1170T 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, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates “Likely Benign.” In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: 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 for S1170T, and this conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500											-3.771	Likely Benign	0.163	Likely Benign	Likely Benign										0.338	Likely Benign	-1.13	Neutral	0.992	Probably Damaging	0.925	Probably Damaging	5.37	Benign	0.08	Tolerated			0.1258	0.5897		1	1	0.1	14.03
c.3539T>C	L1180P 2D AISynGAP1 missense variant L1180P is not reported in ClinVar and has no entry 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus prediction and the higher number of benign calls, suggests 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	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-4.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.213	Likely Benign	-1.37	Neutral	0.992	Probably Damaging	0.930	Probably Damaging	2.65	Benign	0.00	Affected			0.3556	0.1155		-3	-3	-5.4	-16.04
c.3546G>C	E1182D 2D AIThe SynGAP1 missense variant E1182D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict. High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates benign, while the SGM‑Consensus (majority vote) also favors 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, 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	0.566480	Disordered	0.530232	Binding	0.597	0.651	0.375											-4.400	Likely Benign	0.760	Likely Pathogenic	Likely Benign										0.106	Likely Benign	-0.87	Neutral	0.992	Probably Damaging	0.983	Probably Damaging	2.62	Benign	0.34	Tolerated			0.1480	0.4161		3	2	0.0	-14.03
c.3546G>T	E1182D 2D AIThe SynGAP1 missense change E1182D is not reported in ClinVar and has no allele in gnomAD. 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 high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign.” Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of ClinVar annotation or gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.530232	Binding	0.597	0.651	0.375											-4.400	Likely Benign	0.760	Likely Pathogenic	Likely Benign										0.106	Likely Benign	-0.87	Neutral	0.992	Probably Damaging	0.983	Probably Damaging	2.62	Benign	0.34	Tolerated			0.1480	0.4161		3	2	0.0	-14.03
c.3564T>A	D1188E 2D AIThe SynGAP1 missense variant D1188E is 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. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic, whereas the SGM Consensus (majority vote from 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. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic interpretation. The variant is most likely pathogenic based on the consensus of computational tools, 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 Benign	Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-2.517	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-1.93	Neutral	0.992	Probably Damaging	0.992	Probably Damaging	5.50	Benign	0.00	Affected			0.0954	0.4616		3	2	0.0	14.03
c.3564T>G	D1188E 2D AIThe SynGAP1 missense variant D1188E is 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. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy predictors give a mixed picture: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this residue. Overall, five of the nine evaluated tools predict pathogenicity while four predict benignity, with the high‑accuracy AlphaMissense‑Optimized result supporting the pathogenic prediction. Therefore, the variant is most likely pathogenic based on the 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 Benign	Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-2.517	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-1.93	Neutral	0.992	Probably Damaging	0.992	Probably Damaging	5.50	Benign	0.00	Affected			0.0954	0.4616		3	2	0.0	14.03
c.3567G>C	E1189D 2D AIThe SynGAP1 missense variant E1189D (gnomAD ID 6-33444602‑G‑C) is listed in ClinVar as Benign (ClinVar ID 833989.0). In silico predictors that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Predictors that indicate a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. The high‑accuracy AlphaMissense‑Optimized tool classifies the variant as benign, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also favors a benign outcome. No Foldetta stability assessment is available for this residue. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar designation, showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.562014	Disordered	0.466885	Uncertain	0.704	0.623	0.625					Likely Benign		1	6-33444602-G-C	3	1.86e-6	-3.582	Likely Benign	0.461	Ambiguous	Likely Benign										0.359	Likely Benign	-1.42	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	5.30	Benign	0.25	Tolerated	3.82	4	0.1393	0.2610		3	2	0.0	-14.03
c.3567G>T	E1189D 2D AIThe SynGAP1 missense variant E1189D 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, 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 reinforce the benign prediction: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, while Foldetta data are missing. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.562014	Disordered	0.466885	Uncertain	0.704	0.623	0.625											-3.582	Likely Benign	0.461	Ambiguous	Likely Benign										0.359	Likely Benign	-1.42	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	5.30	Benign	0.25	Tolerated	3.82	4	0.1393	0.2610		3	2	0.0	-14.03
c.3575T>A	L1192Q 2D AIThe SynGAP1 missense variant L1192Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) 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 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 from multiple prediction algorithms and consensus methods points to a benign impact for this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-3.804	Likely Benign	0.535	Ambiguous	Likely Benign										0.224	Likely Benign	-1.09	Neutral	0.992	Probably Damaging	0.940	Probably Damaging	2.70	Benign	0.10	Tolerated			0.1032	0.0558		-2	-2	-7.3	14.97
c.3575T>G	L1192R 2D AIThe SynGAP1 missense variant L1192R is not reported in ClinVar and has no entries in gnomAD. Functional 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, 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, 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 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	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-3.221	Likely Benign	0.695	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.33	Neutral	0.992	Probably Damaging	0.940	Probably Damaging	2.75	Benign	0.35	Tolerated			0.1148	0.0558		-3	-2	-8.3	43.03
c.3577G>T	D1193Y 2D AIThe SynGAP1 missense variant D1193Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375											-8.233	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous										0.484	Likely Benign	-2.94	Deleterious	0.992	Probably Damaging	0.947	Probably Damaging	5.50	Benign	0.00	Affected			0.0477	0.4111		-4	-3	2.2	48.09
c.3634T>A	S1212T 2D AIThe SynGAP1 missense variant S1212T is not 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 because it yields a 2‑to‑2 split. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; SGM Consensus is unavailable; Foldetta, which combines FoldX‑MD and Rosetta stability calculations, has no reported output for this variant. Overall, the balance of evidence slightly favors a pathogenic interpretation, but the single high‑accuracy benign prediction and the lack of a consensus from SGM and Foldetta leave the assessment uncertain. There is no conflict with ClinVar status, as the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-4.972	Likely Benign	0.759	Likely Pathogenic	Likely Benign										0.147	Likely Benign	-2.19	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.0997	0.4618		1	1	0.1	14.03
c.3634T>G	S1212A 2D AIThe SynGAP1 missense variant S1212A is not 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, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta results are unavailable. Consequently, the collective evidence points to a benign classification for S1212A, and this conclusion does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.548409	Binding	0.852	0.565	0.500											-4.705	Likely Benign	0.403	Ambiguous	Likely Benign										0.109	Likely Benign	-1.66	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.3901	0.3823		1	1	2.6	-16.00
c.3640C>G	R1214G 2D AIThe SynGAP1 missense variant R1214G is listed in gnomAD (6‑33446632‑C‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized; those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of tools predict a pathogenic impact, and this conclusion is not contradicted by any ClinVar status (none). Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375								6-33446632-C-G	1	6.20e-7	-9.697	Likely Pathogenic	0.725	Likely Pathogenic	Likely Benign										0.131	Likely Benign	-4.41	Deleterious	0.992	Probably Damaging	0.828	Possibly Damaging	2.48	Pathogenic	0.01	Affected	3.77	5	0.3229	0.2361		-2	-3	4.1	-99.14
c.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.3661C>G	R1221G 2D AIThe SynGAP1 missense variant R1221G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the majority of available predictions lean toward a benign impact, with no ClinVar evidence contradicting this assessment. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375											-7.982	In-Between	0.552	Ambiguous	Likely Benign										0.168	Likely Benign	-3.55	Deleterious	0.992	Probably Damaging	0.900	Possibly Damaging	2.54	Benign	0.06	Tolerated			0.3185	0.2110		-3	-2	4.1	-99.14
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.3665G>A	R1222K 2D AIThe SynGAP1 missense variant R1222K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized classifies the change as benign, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus designation but contradicts the benign calls from several other predictors. Thus, based on the current computational predictions, the variant is most likely pathogenic, and this assessment aligns with the lack of ClinVar reporting rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-9.148	Likely Pathogenic	0.689	Likely Pathogenic	Likely Benign										0.249	Likely Benign	-2.05	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.57	Pathogenic	0.54	Tolerated			0.3714	0.2611		3	2	0.6	-28.01
c.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.3731G>C	S1244T 2D AISynGAP1 missense variant S1244T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on benign effect include REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized. Tools that agree on pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments give AlphaMissense‑Optimized a benign score, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, with four high‑confidence pathogenic predictions versus four benign predictions, and the SGM Consensus tipping the scale. This conclusion 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.		Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-9.020	Likely Pathogenic	0.405	Ambiguous	Likely Benign										0.149	Likely Benign	-1.82	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.24	Pathogenic	0.11	Tolerated			0.1129	0.4603		1	1	0.1	14.03
c.3794G>A	R1265K 2D AIThe SynGAP1 missense variant R1265K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive 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. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-5.223	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.344	Likely Benign	-2.49	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.4829	0.3632		3	2	0.6	-28.01
c.3805G>C	V1269L 2D AIThe SynGAP1 missense variant V1269L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.572	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.299	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0683	0.4082		2	1	-0.4	14.03
c.3805G>T	V1269L 2D AIThe SynGAP1 missense variant V1269L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.572	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.299	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0683	0.4082		2	1	-0.4	14.03
c.3806T>C	V1269A 2D AIThe SynGAP1 missense variant V1269A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a larger group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and no Foldetta data. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-6.115	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.38	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.2699	0.2312		0	0	-2.4	-28.05
c.3810G>C	E1270D 2D AIThe SynGAP1 missense variant E1270D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-9.379	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1655	0.3271		3	2	0.0	-14.03
c.3810G>T	E1270D 2D AIThe SynGAP1 missense variant E1270D is catalogued in gnomAD (6-33447858‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence indicates that E1270D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250								6-33447858-G-T			-9.379	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1655	0.3271		3	2	0.0	-14.03
c.3816G>C	E1272D 2D AIThe SynGAP1 missense variant E1272D has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments further show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect. There is no ClinVar classification to contradict this conclusion, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-4.781	Likely Benign	0.751	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.1450	0.3471		2	3	0.0	-14.03
c.3816G>T	E1272D 2D AIThe SynGAP1 missense variant E1272D is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33447864‑G‑T). Functional prediction tools show mixed results: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized tool classifies the change as benign, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. No Foldetta stability assessment is available for this variant. Overall, the majority of conventional predictors and the consensus score lean toward pathogenicity, which is consistent with the SGM‑Consensus designation but contradicts the benign calls from AlphaMissense‑Optimized and a few other tools. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion aligns with the SGM‑Consensus prediction rather than the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500								6-33447864-G-T			-4.781	Likely Benign	0.751	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.1450	0.3471		2	3	0.0	-14.03
c.3875T>A	L1292H 2D AIThe SynGAP1 missense variant L1292H is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33447923‑T‑A). 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 takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are split, with a slight tilt toward pathogenicity (five pathogenic vs. four benign). Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625								6-33447923-T-A			-5.692	Likely Benign	0.335	Likely Benign	Likely Benign										0.202	Likely Benign	-4.42	Deleterious	0.992	Probably Damaging	0.820	Possibly Damaging	2.46	Pathogenic	0.00	Affected	3.77	5	0.1271	0.0649		-3	-2	-7.0	23.98
c.3881C>G	A1294G 2D AIThe SynGAP1 missense variant A1294G is not 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 (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (AlphaMissense‑Optimized) indicate a benign outcome, while the consensus of other tools is split. 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.			0.784345	Disordered	0.895011	Binding	0.565	0.806	0.625											-3.242	Likely Benign	0.132	Likely Benign	Likely Benign										0.201	Likely Benign	-3.06	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.1980	0.2695		1	0	-2.2	-14.03
c.3886G>C	E1296Q 2D AIThe SynGAP1 missense variant E1296Q 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, 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		0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625											-2.510	Likely Benign	0.286	Likely Benign	Likely Benign										0.148	Likely Benign	-2.11	Neutral	0.992	Probably Damaging	0.868	Possibly Damaging	2.60	Benign	0.03	Affected			0.0978	0.5736		2	2	0.0	-0.98
c.3887A>G	E1296G 2D AIThe SynGAP1 missense variant E1296G is 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, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, 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. 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		0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625											-2.864	Likely Benign	0.221	Likely Benign	Likely Benign										0.204	Likely Benign	-5.10	Deleterious	0.992	Probably Damaging	0.868	Possibly Damaging	2.56	Benign	0.01	Affected			0.2971	0.5231		0	-2	3.1	-72.06
c.3887A>T	E1296V 2D AIThe SynGAP1 missense variant E1296V is not 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, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. High‑accuracy predictions therefore indicate a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus is benign, and no Foldetta data are available. Based on the collective predictions, 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.			0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625											-3.384	Likely Benign	0.443	Ambiguous	Likely Benign										0.229	Likely Benign	-4.24	Deleterious	0.992	Probably Damaging	0.902	Possibly Damaging	2.62	Benign	0.01	Affected			0.0678	0.6040		-2	-2	7.7	-29.98
c.3896T>A	L1299H 2D AIThe SynGAP1 missense variant L1299H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect 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. Based on the collective predictions, 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		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750											-4.586	Likely Benign	0.300	Likely Benign	Likely Benign										0.317	Likely Benign	-3.83	Deleterious	0.992	Probably Damaging	0.750	Possibly Damaging	2.67	Benign	0.00	Affected			0.1293	0.1273		-2	-3	-7.0	23.98
c.3955G>C	A1319P 2D AIThe SynGAP1 missense variant A1319P is reported in ClinVar as “Not submitted” and is present in gnomAD (ID 6‑33451829‑G‑C). 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 (majority vote from 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 the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.960481	Binding	0.454	0.851	0.750								6-33451829-G-C	3	1.95e-6	-2.783	Likely Benign	0.057	Likely Benign	Likely Benign										0.104	Likely Benign	-0.81	Neutral	0.992	Probably Damaging	0.878	Possibly Damaging	4.06	Benign	0.03	Affected	3.77	5	0.2360	0.5715		-1	1	-3.4	26.04
c.533A>T	K178M 2D AIThe SynGAP1 missense variant K178M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-13.585	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-3.95	Deleterious	0.992	Probably Damaging	0.751	Possibly Damaging	3.83	Benign	0.00	Affected			0.1486	0.3607		0	-1	5.8	3.02
c.568A>T	S190C 2D AIThe SynGAP1 missense variant S190C is 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, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments reinforce the benign consensus: 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. 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 is not contradicted by any ClinVar 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											-6.696	Likely Benign	0.617	Likely Pathogenic	Likely Benign										0.107	Likely Benign	-2.04	Neutral	0.992	Probably Damaging	0.707	Possibly Damaging	4.01	Benign	0.23	Tolerated			0.0937	0.6667		0	-1	3.3	16.06
c.587T>G	L196W 2D AIThe SynGAP1 missense variant L196W has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for this variant, 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		0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-12.148	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.293	Likely Benign	-4.91	Deleterious	0.992	Probably Damaging	0.869	Possibly Damaging	3.58	Benign	0.00	Affected			0.0551	0.2718		-2	-2	-4.7	73.05
c.59C>A	P20H 2D AIThe SynGAP1 missense variant P20H is reported in gnomAD (ID 6‑33420323‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates benign. Foldetta results are unavailable. Overall, the preponderance of evidence from both consensus and high‑accuracy tools points to a benign effect for P20H, and this conclusion does not contradict any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.442804	Uncertain	0.448	0.899	0.500								6-33420323-C-A			-4.450	Likely Benign	0.352	Ambiguous	Likely Benign										0.132	Likely Benign	-0.69	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	4.23	Benign	0.00	Affected	4.32	1	0.1834	0.5066		-2	0	-1.6	40.02
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.80C>A	P27H 2D AIThe SynGAP1 missense variant P27H is 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 P27H, 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		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375											-4.116	Likely Benign	0.177	Likely Benign	Likely Benign										0.128	Likely Benign	-2.46	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	3.79	Benign	0.00	Affected			0.2384	0.5290		0	-2	-1.6	40.02
c.886T>A	S296T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S296T missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors shows a split: six tools (REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT) and AlphaMissense‑Optimized predict a benign effect, whereas four tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default) predict pathogenicity. ESM1b remains uncertain. High‑accuracy assessments give a more definitive picture: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a benign 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.		C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250											-7.020	In-Between	0.645	Likely Pathogenic	Likely Benign	0.09	Likely Benign	0.4	0.38	Likely Benign	0.24	Likely Benign	0.19	Likely Benign	0.201	Likely Benign	-2.10	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.13	Pathogenic	0.13	Tolerated			0.1437	0.6340		1	1	0.1	14.03
c.886T>G	S296A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S296A (ClinVar ID 469166.0) is listed as ClinVar status Uncertain and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or neutral. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a benign effect. No evidence from the available tools suggests a deleterious impact. Therefore, the variant is most likely benign, and this conclusion is consistent with its ClinVar status of Uncertain rather than pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250					Uncertain		1				-6.847	Likely Benign	0.247	Likely Benign	Likely Benign	0.50	Ambiguous	0.3	-0.26	Likely Benign	0.12	Likely Benign	0.35	Likely Benign	0.209	Likely Benign	-1.79	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.97	Pathogenic	0.65	Tolerated	3.40	16	0.4958	0.5522		1	1	2.6	-16.00	182.5	26.6	-0.2	0.1	-0.5	0.0		X						Potentially Pathogenic	The hydroxyl group of the Ser296 side chain, located in an anti-parallel β sheet strand (res. Met289-Pro298), stably hydrogen bonds with the carboxylate group of Asp330 in a neighboring β strand (res. Ala322-Asp332). The backbone carbonyl group of Ser296 also hydrogen bonds with the guanidinium group of Arg279 in another nearby β strand (res. Arg279-Cys285). In the variant simulations, the methyl group of the Ala296 side chain cannot hydrogen bond with Asp330, causing the carboxylate group positioning to fluctuate more than in the WT simulations.Although the residue swap does not seem to affect the anti-parallel β sheet assembly during the simulations, it is possible that the Ser296-Asp330 hydrogen bond plays a crucial role in maintaining the C2 domain fold. Notably, because Ser296 is located near the membrane interface, the potential effect of the residue swap on the SynGAP-membrane association cannot be addressed by solvent-only simulations.
c.901G>T	A301S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301S is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess sequence conservation and functional impact uniformly indicate a benign effect: SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy methods corroborate the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. No evidence from these analyses suggests a deleterious effect. Therefore, the variant is most likely benign, 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 Benign	C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-2.488	Likely Benign	0.066	Likely Benign	Likely Benign	0.20	Likely Benign	0.1	-0.32	Likely Benign	-0.06	Likely Benign	0.22	Likely Benign	0.151	Likely Benign	-0.28	Neutral	0.992	Probably Damaging	0.983	Probably Damaging	4.21	Benign	0.13	Tolerated			0.2706	0.6022		1	1	-2.6	16.00
c.902C>G	A301G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as Benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, classifies the variant as Benign. Overall, the consensus of the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar claim. Therefore, 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	C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-3.085	Likely Benign	0.072	Likely Benign	Likely Benign	0.27	Likely Benign	0.1	0.34	Likely Benign	0.31	Likely Benign	0.37	Likely Benign	0.128	Likely Benign	-0.37	Neutral	0.992	Probably Damaging	0.983	Probably Damaging	4.18	Benign	0.28	Tolerated			0.2425	0.5054		1	0	-2.2	-14.03
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>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>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.1034T>A	L345Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L345Q is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into benign (REVEL, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM). FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is unavailable. Overall, the majority of predictions lean toward pathogenicity, while the single high‑accuracy tool that is definitive is benign. Thus, the variant is most likely pathogenic based on the collective evidence, 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.		C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-6.034	Likely Benign	0.213	Likely Benign	Likely Benign	1.32	Ambiguous	0.1	0.86	Ambiguous	1.09	Ambiguous	1.26	Destabilizing	0.218	Likely Benign	-3.67	Deleterious	0.993	Probably Damaging	0.844	Possibly Damaging	1.82	Pathogenic	0.03	Affected			0.0937	0.0842		-2	-2	-7.3	14.97
c.1034T>G	L345R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L345R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict pathogenicity: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic prediction. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-10.325	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	0.96	Ambiguous	0.1	1.66	Ambiguous	1.31	Ambiguous	1.28	Destabilizing	0.247	Likely Benign	-3.98	Deleterious	0.993	Probably Damaging	0.796	Possibly Damaging	1.81	Pathogenic	0.04	Affected			0.1140	0.0685		-3	-2	-8.3	43.03
c.1066C>A	R356S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R356S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and SIFT, whereas the remaining tools—premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive. Taken together, the preponderance of evidence points to a pathogenic effect for R356S, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250											-13.059	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	0.79	Ambiguous	0.90	Ambiguous	1.04	Destabilizing	0.292	Likely Benign	-5.28	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	1.84	Pathogenic	0.07	Tolerated			0.2891	0.4491		0	-1	3.7	-69.11
c.1066C>G	R356G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R356G 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 are REVEL and SIFT, while the majority of tools predict a pathogenic outcome: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are uncertain and therefore treated as unavailable evidence. 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 preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250											-12.305	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	1.02	Ambiguous	0.0	1.80	Ambiguous	1.41	Ambiguous	1.06	Destabilizing	0.271	Likely Benign	-6.20	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	1.95	Pathogenic	0.08	Tolerated			0.3505	0.3793		-3	-2	4.1	-99.14
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.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>G	F358V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F358V 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, is classified as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F358V, 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											-9.021	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	1.42	Ambiguous	0.2	1.68	Ambiguous	1.55	Ambiguous	0.93	Ambiguous	0.408	Likely Benign	-5.32	Deleterious	0.993	Probably Damaging	0.968	Probably Damaging	4.09	Benign	0.18	Tolerated			0.2222	0.2978		-1	-1	1.4	-48.04
c.1073T>A	F358Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F358Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a Likely Benign result (3 benign vs. 1 pathogenic), and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a benign effect. premPS is uncertain and is treated as unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-6.458	Likely Benign	0.606	Likely Pathogenic	Likely Benign	0.42	Likely Benign	0.1	0.21	Likely Benign	0.32	Likely Benign	0.84	Ambiguous	0.231	Likely Benign	-2.17	Neutral	0.993	Probably Damaging	0.952	Probably Damaging	4.05	Benign	0.36	Tolerated			0.1467	0.2697		7	3	-4.1	16.00
c.1228A>T	S410C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S410C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict it as pathogenic are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. 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											-7.552	In-Between	0.144	Likely Benign	Likely Benign	-0.24	Likely Benign	0.1	0.31	Likely Benign	0.04	Likely Benign	0.22	Likely Benign	0.230	Likely Benign	-3.10	Deleterious	0.993	Probably Damaging	0.536	Possibly Damaging	4.12	Benign	0.11	Tolerated			0.1041	0.6543		0	-1	3.3	16.06
c.1229G>T	S410I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S410I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are uncertain or inconclusive are FoldX, Foldetta, and AlphaMissense‑Default. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans pathogenic, and Foldetta remains uncertain. Overall, the majority of tools suggest a benign impact, but the high‑accuracy consensus indicates potential pathogenicity, leaving the variant’s effect ambiguous. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for it. 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											-9.383	Likely Pathogenic	0.432	Ambiguous	Likely Benign	-1.08	Ambiguous	0.2	-0.36	Likely Benign	-0.72	Ambiguous	-0.41	Likely Benign	0.114	Likely Benign	-3.21	Deleterious	0.993	Probably Damaging	0.589	Possibly Damaging	4.15	Benign	0.21	Tolerated			0.0965	0.6579		-1	-2	5.3	26.08
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>G	H453R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant H453R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an inconclusive result because FoldX is uncertain and Rosetta is benign. Overall, the balance of evidence favors a pathogenic interpretation, 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	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-9.239	Likely Pathogenic	0.573	Likely Pathogenic	Likely Benign	-0.52	Ambiguous	0.1	0.37	Likely Benign	-0.08	Likely Benign	0.56	Ambiguous	0.396	Likely Benign	-7.91	Deleterious	0.993	Probably Damaging	0.957	Probably Damaging	3.53	Benign	0.39	Tolerated			0.1646	0.2031		2	0	-1.3	19.05
c.1512A>C	K504N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K504N is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8/13) predict pathogenicity, while 4 predict benign and one is uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-8.908	Likely Pathogenic	0.720	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	0.57	Ambiguous	0.42	Likely Benign	1.00	Destabilizing	0.430	Likely Benign	-4.37	Deleterious	0.993	Probably Damaging	0.922	Probably Damaging	-1.44	Pathogenic	0.07	Tolerated			0.2470	0.0926		1	0	0.4	-14.07
c.1512A>T	K504N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K504N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, AlphaMissense‑Optimized, and the folding‑stability method Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it likely pathogenic, and Foldetta indicating a benign folding‑stability outcome. Overall, the majority of predictions (8 out of 13) support a pathogenic interpretation. Thus, 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	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-8.908	Likely Pathogenic	0.720	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	0.57	Ambiguous	0.42	Likely Benign	1.00	Destabilizing	0.430	Likely Benign	-4.37	Deleterious	0.993	Probably Damaging	0.922	Probably Damaging	-1.44	Pathogenic	0.07	Tolerated			0.2470	0.0926		1	0	0.4	-14.07
c.1600T>C	S534P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438843‑T‑C). Functional prediction tools that report a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy assessments are consistent with a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the aggregate predictions, the variant is most likely benign, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000					Uncertain		1	6-33438843-T-C	3	1.86e-6	-5.056	Likely Benign	0.265	Likely Benign	Likely Benign	-0.40	Likely Benign	0.2	0.35	Likely Benign	-0.03	Likely Benign	0.47	Likely Benign	0.203	Likely Benign	-3.81	Deleterious	0.993	Probably Damaging	0.993	Probably Damaging	3.32	Benign	0.05	Affected	3.37	35	0.2071	0.4650		-1	1	-0.8	10.04
c.1613A>G	E538G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No folding‑stability result is definitive. Overall, the balance of evidence, including the majority‑vote SGM Consensus and the higher number of pathogenic predictions, points to a pathogenic effect for E538G. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-9.258	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	0.91	Ambiguous	0.0	1.07	Ambiguous	0.99	Ambiguous	0.31	Likely Benign	0.285	Likely Benign	-5.10	Deleterious	0.993	Probably Damaging	0.700	Possibly Damaging	3.33	Benign	0.03	Affected			0.3173	0.3713		0	-2	3.1	-72.06
c.1706T>A	F569Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F569Y missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive, providing no definitive evidence for either outcome. High‑accuracy assessments show that the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) strongly supports pathogenicity, while AlphaMissense‑Optimized remains uncertain and Foldetta likewise yields an inconclusive result. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-11.101	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.57	Ambiguous	0.1	0.82	Ambiguous	1.20	Ambiguous	1.29	Destabilizing	0.824	Likely Pathogenic	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.37	Pathogenic	0.08	Tolerated			0.1379	0.1170		7	3	-4.1	16.00
c.1753G>T	A585S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A585S is not reported in ClinVar (no entry) and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts Likely Benign, while Foldetta remains uncertain. Overall, the majority of evidence supports a benign classification, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-6.332	Likely Benign	0.246	Likely Benign	Likely Benign	0.91	Ambiguous	0.2	1.44	Ambiguous	1.18	Ambiguous	0.02	Likely Benign	0.326	Likely Benign	0.39	Neutral	0.993	Probably Damaging	0.996	Probably Damaging	-1.27	Pathogenic	0.98	Tolerated			0.2121	0.3388		1	1	-2.6	16.00
c.1781T>A	F594Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to Rosetta, which scores the substitution as benign. In contrast, the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, SGM‑Consensus, and premPS all classify the variant as pathogenic. FoldX and Foldetta are uncertain, and AlphaMissense‑Optimized is also uncertain, so these results are treated as unavailable. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence indicates that F594Y is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000											-13.692	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.30	Ambiguous	0.2	0.41	Likely Benign	0.86	Ambiguous	1.21	Destabilizing	0.929	Likely Pathogenic	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.98	Pathogenic	0.01	Affected			0.1264	0.0731		7	3	-4.1	16.00
c.1790T>A	F597Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F597Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include ESM1b and Rosetta, whereas a majority of tools (REVEL, SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, PROVEAN, premPS, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F597Y. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000											-5.869	Likely Benign	0.796	Likely Pathogenic	Ambiguous	1.41	Ambiguous	0.1	0.37	Likely Benign	0.89	Ambiguous	1.11	Destabilizing	0.877	Likely Pathogenic	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.99	Pathogenic	0.02	Affected			0.1471	0.1494		7	3	-4.1	16.00
c.1823T>A	F608Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F608Y is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a pathogenic effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus all predict pathogenicity, while only Rosetta predicts a benign effect. Tools with uncertain outcomes—FoldX, Foldetta, and AlphaMissense‑Optimized—do not provide decisive evidence. High‑accuracy assessments further support a deleterious impact: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic, whereas AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence indicates that F608Y 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	0.106997	Structured	0.197190	Uncertain	0.891	0.247	0.000											-13.249	Likely Pathogenic	0.812	Likely Pathogenic	Ambiguous	0.62	Ambiguous	0.1	0.41	Likely Benign	0.52	Ambiguous	1.05	Destabilizing	0.747	Likely Pathogenic	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.44	Pathogenic	0.00	Affected			0.1504	0.1346		7	3	-4.1	16.00
c.1903A>C	N635H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N635H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Three tools (FoldX, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; and Foldetta predicts benign. No prediction or folding‑stability result is missing or inconclusive. Based on the available evidence, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.060246	Uncertain	0.900	0.252	0.000											-12.507	Likely Pathogenic	0.419	Ambiguous	Likely Benign	1.07	Ambiguous	0.2	-0.10	Likely Benign	0.49	Likely Benign	0.91	Ambiguous	0.429	Likely Benign	-4.78	Deleterious	0.993	Probably Damaging	0.879	Possibly Damaging	2.90	Benign	0.00	Affected			0.1184	0.3720		2	1	0.3	23.04
c.1983G>C	Q661H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q661H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-9.938	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.1	0.07	Likely Benign	0.43	Likely Benign	0.09	Likely Benign	0.282	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.42	Benign	0.02	Affected			0.1276	0.3424		3	0	0.3	9.01
c.1983G>T	Q661H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q661H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000											-9.938	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.78	Ambiguous	0.1	0.07	Likely Benign	0.43	Likely Benign	0.09	Likely Benign	0.282	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.42	Benign	0.02	Affected			0.1276	0.3424		3	0	0.3	9.01
c.1990T>G	L664V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta and Foldetta are uncertain, providing no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic (3 pathogenic vs 1 benign). Foldetta’s stability prediction is uncertain. Overall, the majority of reliable tools predict a pathogenic impact. Therefore, 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	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000											-11.515	Likely Pathogenic	0.755	Likely Pathogenic	Likely Benign	2.01	Destabilizing	0.1	1.13	Ambiguous	1.57	Ambiguous	1.37	Destabilizing	0.378	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.776	Possibly Damaging	2.91	Benign	0.01	Affected			0.0984	0.2628		2	1	0.4	-14.03
c.2009T>G	L670R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign effect. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.801	Likely Pathogenic	0.552	Ambiguous	Likely Benign	0.64	Ambiguous	0.1	1.42	Ambiguous	1.03	Ambiguous	0.67	Ambiguous	0.193	Likely Benign	-1.74	Neutral	0.993	Probably Damaging	0.755	Possibly Damaging	3.43	Benign	0.41	Tolerated			0.1327	0.1145		-3	-2	-8.3	43.03
c.2015C>T	T672M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T672M is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441274‑C‑T). Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Rosetta and Foldetta report uncertain results, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta remain unavailable. Overall, the balance of evidence favors a benign effect, and this conclusion does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000					Conflicting		3	6-33441274-C-T	19	1.18e-5	-9.472	Likely Pathogenic	0.174	Likely Benign	Likely Benign	0.31	Likely Benign	0.4	1.52	Ambiguous	0.92	Ambiguous	0.41	Likely Benign	0.127	Likely Benign	-4.34	Deleterious	0.993	Probably Damaging	0.520	Possibly Damaging	3.39	Benign	0.00	Affected	3.40	25	0.1332	0.6677		-1	-1	2.6	30.09	231.9	-52.9	1.1	0.1	0.5	0.0		X				X		Potentially Pathogenic	The hydroxyl group of Thr672, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop itself, such as Lys566, Glu666, and Asn669. Met672 can only form a hydrogen bond with the amino group of the Lys566 side chain via its backbone carbonyl group. Nevertheless, the Lys566-Glu666 salt bridge forms intermittently. This is possible because Asn669 keeps the carboxylate group of Glu666 in the vicinity through hydrogen bonding, and the hydrophobic side chain of Met stays mostly rotated away from the salt bridge. Consequently, no drastic disruption of the hydrogen-bond network that keeps the loop close to the helices occurs in the variant simulations.
c.2024A>G	N675S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, FATHMM, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools (premPS and ESM1b) return uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign consensus; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Taken together, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-7.871	In-Between	0.081	Likely Benign	Likely Benign	0.37	Likely Benign	0.0	-0.43	Likely Benign	-0.03	Likely Benign	0.61	Ambiguous	0.157	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.606	Possibly Damaging	3.50	Benign	0.11	Tolerated			0.3462	0.7587		1	1	2.7	-27.03
c.2025C>A	N675K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N675K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, and FATHMM, whereas pathogenic calls are made by FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported for Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-12.851	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous	2.88	Destabilizing	1.2	0.06	Likely Benign	1.47	Ambiguous	0.74	Ambiguous	0.177	Likely Benign	-4.75	Deleterious	0.993	Probably Damaging	0.688	Possibly Damaging	3.44	Benign	0.02	Affected			0.2424	0.6040		1	0	-0.4	14.07
c.2025C>G	N675K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Tools with inconclusive results are Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic classification for N675K, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-12.851	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous	2.88	Destabilizing	1.2	0.06	Likely Benign	1.47	Ambiguous	0.74	Ambiguous	0.177	Likely Benign	-4.75	Deleterious	0.993	Probably Damaging	0.688	Possibly Damaging	3.44	Benign	0.02	Affected			0.2424	0.6040		1	0	-0.4	14.07
c.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>G	F679V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta provide inconclusive results and are treated as unavailable. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-11.868	Likely Pathogenic	0.900	Likely Pathogenic	Ambiguous	1.92	Ambiguous	0.5	0.29	Likely Benign	1.11	Ambiguous	0.89	Ambiguous	0.497	Likely Benign	-6.86	Deleterious	0.993	Probably Damaging	0.968	Probably Damaging	3.50	Benign	0.01	Affected			0.1830	0.2349		-1	-1	1.4	-48.04
c.2036T>A	F679Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools give uncertain results: premPS and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the majority of evidence indicates that F679Y is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-5.842	Likely Benign	0.462	Ambiguous	Likely Benign	0.48	Likely Benign	0.2	0.13	Likely Benign	0.31	Likely Benign	0.71	Ambiguous	0.315	Likely Benign	-2.71	Deleterious	0.993	Probably Damaging	0.952	Probably Damaging	3.47	Benign	0.14	Tolerated			0.1306	0.1954		7	3	-4.1	16.00
c.2053T>G	L685V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability methods provide definitive evidence. Overall, the preponderance of pathogenic predictions, including the SGM Consensus, suggests that the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-11.418	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.87	Ambiguous	0.0	1.15	Ambiguous	1.51	Ambiguous	0.97	Ambiguous	0.214	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.33	Benign	0.02	Affected			0.1414	0.3010		2	1	0.4	-14.03
c.2057G>C	G686A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy methods give a pathogenic verdict from AlphaMissense‑Optimized and a Likely Pathogenic consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), while Foldetta predicts benign stability. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000											-9.975	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	-0.39	Likely Benign	0.2	-0.46	Likely Benign	-0.43	Likely Benign	0.58	Ambiguous	0.321	Likely Benign	-5.19	Deleterious	0.993	Probably Damaging	0.732	Possibly Damaging	3.37	Benign	0.13	Tolerated			0.3744	0.4131		1	0	2.2	14.03
c.2072C>G	T691R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Benign, SGM Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000											-12.228	Likely Pathogenic	0.621	Likely Pathogenic	Likely Benign	-1.27	Ambiguous	0.3	-0.94	Ambiguous	-1.11	Ambiguous	1.35	Destabilizing	0.180	Likely Benign	-3.66	Deleterious	0.993	Probably Damaging	0.566	Possibly Damaging	3.48	Benign	0.02	Affected			0.0729	0.2478		-1	-1	-3.8	55.08
c.2083C>G	L695V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta is also unavailable. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-10.605	Likely Pathogenic	0.317	Likely Benign	Likely Benign	1.61	Ambiguous	0.0	1.57	Ambiguous	1.59	Ambiguous	1.19	Destabilizing	0.274	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.20	Benign	0.02	Affected			0.1158	0.2828		2	1	0.4	-14.03
c.2084T>G	L695R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the variant as pathogenic. AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also pathogenic. Overall, the evidence overwhelmingly indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-15.582	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	2.05	Destabilizing	0.1	2.66	Destabilizing	2.36	Destabilizing	1.57	Destabilizing	0.605	Likely Pathogenic	-5.92	Deleterious	0.993	Probably Damaging	0.588	Possibly Damaging	3.17	Benign	0.00	Affected			0.1220	0.0530		-3	-2	-8.3	43.03
c.2173C>G	L725V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The remaining methods (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta provides no definitive stability change. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-8.291	Likely Pathogenic	0.461	Ambiguous	Likely Benign	1.76	Ambiguous	0.1	1.87	Ambiguous	1.82	Ambiguous	0.77	Ambiguous	0.183	Likely Benign	-2.69	Deleterious	0.993	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.01	Affected			0.1739	0.3977		2	1	0.4	-14.03
c.2190C>G	I730M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I730M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs)—all uniformly indicate a benign impact. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.420109	Uncertain	0.591	0.619	0.750											-3.149	Likely Benign	0.110	Likely Benign	Likely Benign	-0.15	Likely Benign	0.1	0.31	Likely Benign	0.08	Likely Benign	-0.15	Likely Benign	0.042	Likely Benign	-0.77	Neutral	0.993	Probably Damaging	0.914	Probably Damaging	3.43	Benign	0.09	Tolerated			0.0698	0.2159		2	1	-2.6	18.03
c.2218C>G	R740G 2D AIThe SynGAP1 missense variant R740G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. 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 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		0.771762	Disordered	0.475392	Uncertain	0.269	0.849	0.875											-4.556	Likely Benign	0.117	Likely Benign	Likely Benign										0.138	Likely Benign	-2.55	Deleterious	0.993	Probably Damaging	0.887	Possibly Damaging	2.56	Benign	0.03	Affected			0.3739	0.3149		-3	-2	4.1	-99.14
c.2255C>T	S752L 2D AIThe SynGAP1 missense variant S752L is listed in ClinVar with an “Uncertain” status (ClinVar ID 2143952.0) and is present in gnomAD (ID 6‑33441720‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.690594	Binding	0.365	0.877	0.625					Uncertain		2	6-33441720-C-T	6	3.72e-6	-3.386	Likely Benign	0.182	Likely Benign	Likely Benign										0.195	Likely Benign	-2.09	Neutral	0.993	Probably Damaging	0.641	Possibly Damaging	1.51	Pathogenic	0.01	Affected	3.99	5	0.1308	0.5909		-3	-2	4.6	26.08
c.2518A>C	S840R 2D AIThe SynGAP1 missense variant S840R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that S840R is most likely pathogenic, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.366	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-3.27	Deleterious	0.993	Probably Damaging	0.904	Possibly Damaging	1.51	Pathogenic	0.00	Affected			0.0726	0.3328		0	-1	-3.7	69.11
c.2520T>A	S840R 2D AIThe SynGAP1 missense variant S840R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign, representing the sole benign prediction. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized returns a pathogenic score, and the SGM‑Consensus indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from multiple in silico tools and high‑accuracy predictors indicates that S840R is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.366	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.244	Likely Benign	-3.27	Deleterious	0.993	Probably Damaging	0.904	Possibly Damaging	1.51	Pathogenic	0.00	Affected			0.0726	0.3328		0	-1	-3.7	69.11
c.2520T>G	S840R 2D AIThe SynGAP1 missense variant S840R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign, representing the sole benign prediction. High‑accuracy assessments further support a pathogenic outcome: AlphaMissense‑Optimized returns a pathogenic score, and the SGM‑Consensus indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from multiple in silico tools and high‑accuracy predictors indicates that S840R is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-9.366	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.244	Likely Benign	-3.27	Deleterious	0.993	Probably Damaging	0.904	Possibly Damaging	1.51	Pathogenic	0.00	Affected			0.0726	0.3328		0	-1	-3.7	69.11
c.310C>T	R104C 2D AIThe SynGAP1 missense variant R104C has no ClinVar entry and is present in gnomAD (ID 6‑33432175‑C‑T). 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; the Foldetta protein‑folding 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		0.795062	Disordered	0.678998	Binding	0.339	0.869	0.625								6-33432175-C-T	2	1.24e-6	-5.716	Likely Benign	0.475	Ambiguous	Likely Benign										0.109	Likely Benign	-1.41	Neutral	0.993	Probably Damaging	0.446	Benign	3.99	Benign	0.00	Affected	4.32	1	0.2954	0.3292		-3	-4	7.0	-53.05																10.1016/j.ajhg.2020.11.011
c.3184G>T	G1062W 2D AIThe SynGAP1 missense variant G1062W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which labels the variant as “Likely Benign.” Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b, all of which classify the change as damaging. 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, 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, 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 Benign		0.976962	Disordered	0.936972	Binding	0.368	0.917	0.875											-9.667	Likely Pathogenic	0.315	Likely Benign	Likely Benign										0.401	Likely Benign	-1.38	Neutral	0.993	Probably Damaging	0.890	Possibly Damaging	4.09	Benign	0.00	Affected			0.0908	0.4246		-7	-2	-0.5	129.16
c.322A>G	K108E 2D AIThe SynGAP1 K108E 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 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the predictions are split evenly between benign and pathogenic, with no clear majority. Consequently, the variant’s impact remains uncertain, and there is no contradiction with ClinVar status, which currently lists no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.679	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-1.24	Neutral	0.993	Probably Damaging	0.956	Probably Damaging	4.12	Benign	0.04	Affected			0.4145	0.1166		0	1	0.4	0.94
c.323A>G	K108R 2D AIThe SynGAP1 missense variant K108R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33432188‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, 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		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875					Uncertain		1	6-33432188-A-G	6	3.72e-6	-2.892	Likely Benign	0.148	Likely Benign	Likely Benign										0.184	Likely Benign	0.37	Neutral	0.993	Probably Damaging	0.956	Probably Damaging	4.22	Benign	1.00	Tolerated	3.61	5	0.5286	0.1229	Weaken	3	2	-0.6	28.01
c.3641G>A	R1214Q 2D AIThe SynGAP1 missense variant R1214Q is catalogued in gnomAD (6‑33446633‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise 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 points to a benign effect for R1214Q, and this conclusion is not contradicted by any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375								6-33446633-G-A	6	3.72e-6	-6.059	Likely Benign	0.138	Likely Benign	Likely Benign										0.078	Likely Benign	-1.69	Neutral	0.993	Probably Damaging	0.738	Possibly Damaging	2.65	Benign	0.02	Affected	3.77	5	0.2162	0.1530		1	1	1.0	-28.06
c.371C>A	A124E 2D AIThe SynGAP1 missense variant A124E is 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 for A124E, 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	0.699139	Binding	0.340	0.883	0.750											-3.444	Likely Benign	0.667	Likely Pathogenic	Likely Benign										0.208	Likely Benign	-1.21	Neutral	0.993	Probably Damaging	0.733	Possibly Damaging	4.11	Benign	0.01	Affected			0.1498	0.2233		0	-1	-5.3	58.04
c.409C>A	L137I 2D AIThe SynGAP1 missense variant L137I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 3 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.870	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.22	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.0932	0.3102		2	2	0.7	0.00
c.409C>G	L137V 2D AIThe SynGAP1 missense variant L137V is not 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 takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Thus, 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.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.621	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.118	Likely Benign	-1.75	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.1533	0.2612		2	1	0.4	-14.03
c.448C>A	L150I 2D AIThe SynGAP1 missense variant L150I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a likely pathogenic impact for the variant. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.118	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous										0.080	Likely Benign	-1.25	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.0894	0.3468		2	2	0.7	0.00
c.448C>G	L150V 2D AIThe SynGAP1 missense variant L150V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.375	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.84	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.1473	0.3178		2	1	0.4	-14.03
c.451G>A	D151N 2D AIThe SynGAP1 missense variant D151N has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic. The SGM‑Consensus result (Likely Pathogenic) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors indicates that D151N is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-8.479	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.185	Likely Benign	-2.51	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.90	Benign	0.01	Affected			0.1346	0.8186		2	1	0.0	-0.98
c.452A>G	D151G 2D AIThe SynGAP1 D151G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and FATHMM, whereas the remaining eight tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus confirms a likely pathogenic status. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence indicates that D151G is most likely pathogenic, and this assessment does not conflict with any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-10.409	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.349	Likely Benign	-3.91	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.87	Benign	0.01	Affected			0.4452	0.7037		1	-1	3.1	-58.04
c.454C>G	R152G 2D AIThe SynGAP1 missense variant R152G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R152G is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625											-11.043	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-4.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.83	Benign	0.00	Affected			0.3633	0.3956		-3	-2	4.1	-99.14
c.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.469C>A	R157S 2D AIThe SynGAP1 R157S 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 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 (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic majority vote (2 pathogenic, 1 benign, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R157S 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.			0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-7.573	In-Between	0.977	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-2.82	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.85	Benign	0.00	Affected			0.3484	0.2563		0	-1	3.7	-69.11
c.469C>G	R157G 2D AIThe SynGAP1 R157G missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an Uncertain result, SGM‑Consensus indicates Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-9.125	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.252	Likely Benign	-3.52	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.80	Benign	0.00	Affected			0.3892	0.2567		-3	-2	4.1	-99.14
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.685A>G	K229E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K229E is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include FoldX, Rosetta, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall distribution of predictions, the variant is most likely pathogenic; this conclusion does not contradict the ClinVar status, which currently has no entry for K229E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-12.828	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.47	Likely Benign	0.0	0.24	Likely Benign	0.36	Likely Benign	0.18	Likely Benign	0.816	Likely Pathogenic	-3.10	Deleterious	0.993	Probably Damaging	0.971	Probably Damaging	5.84	Benign	0.09	Tolerated			0.3915	0.0793		0	1	0.4	0.94
c.686A>G	K229R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K229R missense variant is catalogued in gnomAD (ID 6‑33435537‑A‑G) but has no entry in ClinVar. Functional prediction tools largely agree on a benign effect: FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. In contrast, REVEL, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar predict pathogenic. AlphaMissense‑Default is uncertain and is treated as unavailable. The high‑accuracy consensus methods reinforce 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. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000								6-33435537-A-G	1	6.20e-7	-5.651	Likely Benign	0.437	Ambiguous	Likely Benign	0.09	Likely Benign	0.0	0.02	Likely Benign	0.06	Likely Benign	0.40	Likely Benign	0.628	Likely Pathogenic	-2.00	Neutral	0.993	Probably Damaging	0.971	Probably Damaging	5.84	Benign	0.19	Tolerated	3.43	12	0.4921	0.0972		2	3	-0.6	28.01
c.718G>A	D240N 2D AIThe SynGAP1 missense variant D240N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Benign predictions are provided by FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. High‑accuracy methods give a split: AlphaMissense‑Optimized predicts benign, SGM‑Consensus predicts pathogenic, and Foldetta predicts benign. Overall, the majority of tools favor a benign effect, and this consensus does not contradict the ClinVar uncertain status. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000					Uncertain		1				-12.942	Likely Pathogenic	0.755	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.9	0.47	Likely Benign	0.35	Likely Benign	0.37	Likely Benign	0.701	Likely Pathogenic	-4.37	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	5.88	Benign	0.01	Affected			0.0993	0.4973		2	1	0.0	-0.98
c.719A>G	D240G 2D AIThe SynGAP1 missense variant D240G is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Benign predictions are provided by premPS and FATHMM, whereas pathogenic predictions are made by REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. FoldX‑MD is inconclusive, and AlphaMissense‑Optimized is uncertain. High‑accuracy methods show that AlphaMissense‑Optimized is inconclusive, SGM Consensus predicts pathogenic, and Foldetta predicts pathogenic. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the ClinVar uncertain status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000					Uncertain		1				-12.825	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	1.85	Ambiguous	0.1	2.72	Destabilizing	2.29	Destabilizing	0.24	Likely Benign	0.912	Likely Pathogenic	-6.19	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	5.79	Benign	0.01	Affected			0.3474	0.4989		1	-1	3.1	-58.04
c.757A>G	N253D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N253D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on benign effects include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while those that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicating likely pathogenic, whereas Foldetta predicts a benign effect on protein stability. Overall, the majority of tools (8/15) favor a pathogenic outcome, with no conflict with ClinVar status because the variant is not yet catalogued. Thus, the variant is most likely pathogenic based on current computational predictions, and this assessment does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250											-14.105	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.37	Likely Benign	0.31	Likely Benign	0.09	Likely Benign	0.742	Likely Pathogenic	-4.13	Deleterious	0.993	Probably Damaging	0.971	Probably Damaging	5.60	Benign	0.09	Tolerated			0.2248	0.5186		2	1	0.0	0.98
c.758A>C	N253T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N253T is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include premPS, SIFT, and FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic outcome. High‑accuracy methods give a consistent pathogenic signal: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenic. AlphaMissense‑Optimized is uncertain and is treated as unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250											-11.656	Likely Pathogenic	0.929	Likely Pathogenic	Ambiguous	1.96	Ambiguous	0.3	2.67	Destabilizing	2.32	Destabilizing	0.16	Likely Benign	0.739	Likely Pathogenic	-5.01	Deleterious	0.993	Probably Damaging	0.971	Probably Damaging	5.54	Benign	0.06	Tolerated			0.1640	0.8665		0	0	2.8	-13.00
c.758A>G	N253S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N253S is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33435609‑A‑G). Prediction tools that agree on a benign effect include premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the evidence is mixed, but the single high‑accuracy tool that is available points to a benign effect. Therefore, the variant is most likely benign based on current predictions, and this assessment does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250								6-33435609-A-G			-7.197	In-Between	0.541	Ambiguous	Likely Benign	0.60	Ambiguous	0.1	1.19	Ambiguous	0.90	Ambiguous	-0.03	Likely Benign	0.716	Likely Pathogenic	-4.26	Deleterious	0.993	Probably Damaging	0.956	Probably Damaging	5.56	Benign	0.09	Tolerated	3.39	15	0.3960	0.7764		1	1	2.7	-27.03
c.759C>A	N253K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N253K resides in the PH domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Functional prediction tools that classify the variant as benign include FoldX, Foldetta, premPS, and FATHMM. In contrast, the majority of predictors—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)—label it pathogenic or likely pathogenic. The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus also indicates likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect. This assessment is not contradicted by ClinVar, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250											-15.834	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.0	0.90	Ambiguous	0.48	Likely Benign	0.17	Likely Benign	0.663	Likely Pathogenic	-5.21	Deleterious	0.993	Probably Damaging	0.979	Probably Damaging	5.53	Benign	0.03	Affected			0.2640	0.6592		1	0	-0.4	14.07
c.759C>G	N253K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N253K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools fall into two groups: benign predictions come from FoldX, FATHMM, premPS, and Foldetta, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Benign. Overall, the majority of tools predict pathogenicity, and the two most reliable predictors also lean pathogenic, whereas only one high‑accuracy tool suggests benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250											-15.834	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.0	0.90	Ambiguous	0.48	Likely Benign	0.17	Likely Benign	0.663	Likely Pathogenic	-5.21	Deleterious	0.993	Probably Damaging	0.979	Probably Damaging	5.53	Benign	0.03	Affected			0.2640	0.6592		1	0	-0.4	14.07
c.770G>A	S257N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S257N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: benign calls come from FoldX, Rosetta, Foldetta, PROVEAN, SIFT, and FATHMM, while pathogenic calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments give an inconclusive SGM Consensus (a tie between AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), an uncertain AlphaMissense‑Optimized result, and a benign Foldetta prediction. No evidence of pathogenicity is supported by the protein‑stability analysis, which indicates a benign effect. Overall, the predictions are mixed, but the majority of high‑accuracy tools lean toward a benign interpretation. This assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.384043	Structured	0.258293	Uncertain	0.847	0.272	0.250											-10.508	Likely Pathogenic	0.820	Likely Pathogenic	Ambiguous	0.25	Likely Benign	0.1	-0.18	Likely Benign	0.04	Likely Benign	0.85	Ambiguous	0.533	Likely Pathogenic	-2.30	Neutral	0.993	Probably Damaging	0.968	Probably Damaging	5.82	Benign	0.16	Tolerated			0.0985	0.3596		1	1	-2.7	27.03
c.1036G>C	V346L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346L is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Four tools (Foldetta, premPS, AlphaMissense‑Optimized, and Rosetta) give uncertain or inconclusive results and are not used as evidence. 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 reliable predictors and the SGM‑Consensus support a pathogenic effect. Therefore, 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	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-8.178	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous	0.05	Likely Benign	0.2	1.10	Ambiguous	0.58	Ambiguous	0.60	Ambiguous	0.384	Likely Benign	-2.68	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.58	Pathogenic	0.09	Tolerated			0.1237	0.5348		2	1	-0.4	14.03
c.1036G>T	V346L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Four tools (Foldetta, premPS, AlphaMissense‑Optimized, and Rosetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a deleterious effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-8.178	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous	0.05	Likely Benign	0.2	1.10	Ambiguous	0.58	Ambiguous	0.60	Ambiguous	0.386	Likely Benign	-2.68	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.58	Pathogenic	0.09	Tolerated			0.1237	0.5348		2	1	-0.4	14.03
c.1037T>C	V346A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346A is reported in gnomAD (6‑33437942‑T‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect are limited to REVEL, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) uniformly predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000								6-33437942-T-C	1	6.20e-7	-8.556	Likely Pathogenic	0.856	Likely Pathogenic	Ambiguous	2.72	Destabilizing	0.2	2.73	Destabilizing	2.73	Destabilizing	1.92	Destabilizing	0.477	Likely Benign	-3.68	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.70	Pathogenic	0.01	Affected	3.37	25	0.3341	0.2967		0	0	-2.4	-28.05
c.1080G>C	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not 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 SIFT. In contrast, a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus remains Likely Pathogenic, while Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360D. 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	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.1080G>T	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D 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, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.1144G>A	G382R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G382R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include premPS, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts a benign change, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta stability outputs) both predict pathogenicity. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750											-8.997	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	4.53	Destabilizing	1.6	8.03	Destabilizing	6.28	Destabilizing	0.23	Likely Benign	0.595	Likely Pathogenic	-0.95	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			0.1295	0.4346		-3	-2	-4.1	99.14
c.1144G>C	G382R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G382R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include premPS, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts a benign change, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta stability outputs) both predict pathogenicity. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750											-8.997	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	4.53	Destabilizing	1.6	8.03	Destabilizing	6.28	Destabilizing	0.23	Likely Benign	0.570	Likely Pathogenic	-0.95	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			0.1295	0.4346		-3	-2	-4.1	99.14
c.1145G>A	G382E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G382E is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438050‑G‑A). Prediction tools that agree on a benign effect include premPS, PROVEAN, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts pathogenic. Overall, the majority of evidence points to a pathogenic impact for G382E, 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	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750								6-33438050-G-A			-9.570	Likely Pathogenic	0.564	Ambiguous	Likely Benign	4.86	Destabilizing	1.7	6.64	Destabilizing	5.75	Destabilizing	0.48	Likely Benign	0.594	Likely Pathogenic	-0.96	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.03	Affected	4.32	9	0.1775	0.3932		-2	0	-3.1	72.06
c.1145G>T	G382V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G382V has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split opinion: benign predictions come from PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, while premPS is uncertain. High‑accuracy assessments give a mixed signal: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, but Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy Foldetta result supports this. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750											-5.988	Likely Benign	0.155	Likely Benign	Likely Benign	6.40	Destabilizing	1.6	9.28	Destabilizing	7.84	Destabilizing	-0.53	Ambiguous	0.571	Likely Pathogenic	-0.54	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.03	Affected			0.1631	0.3708		-1	-3	4.6	42.08
c.1150G>C	G384R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G384R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls are made by FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but SGM‑Consensus and Foldetta both predict pathogenic, with Foldetta integrating FoldX‑MD and Rosetta stability outputs. Overall, the majority 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	C2	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750											-9.186	Likely Pathogenic	0.719	Likely Pathogenic	Likely Benign	2.16	Destabilizing	0.4	5.06	Destabilizing	3.61	Destabilizing	0.25	Likely Benign	0.475	Likely Benign	-0.96	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			0.1250	0.4156		-3	-2	-4.1	99.14
c.1151G>A	G384D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G384D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33438056‑G‑A). Prediction tools that classify the variant as benign include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that predict pathogenicity are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; premPS is uncertain. Separately, the high‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools—including the high‑accuracy methods—indicate a pathogenic effect. This prediction does not contradict any ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750								6-33438056-G-A			-9.142	Likely Pathogenic	0.610	Likely Pathogenic	Likely Benign	2.06	Destabilizing	0.5	2.15	Destabilizing	2.11	Destabilizing	0.53	Ambiguous	0.439	Likely Benign	-0.93	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	2	0.2071	0.2235		-1	1	-3.1	58.04
c.1151G>T	G384V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G384V is catalogued in gnomAD (ID 6‑33438056‑G‑T) but has no entry in ClinVar. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. 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 benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect on protein stability. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750								6-33438056-G-T			-6.968	Likely Benign	0.131	Likely Benign	Likely Benign	3.69	Destabilizing	0.4	6.77	Destabilizing	5.23	Destabilizing	-0.11	Likely Benign	0.460	Likely Benign	-1.01	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.01	Affected	4.32	2	0.1599	0.3708		-3	-1	4.6	42.08
c.1162G>C	G388R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G388R is 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, PROVEAN, and AlphaMissense‑Optimized, whereas the remaining eleven tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both predict pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overall consensus of the majority of tools and the high‑accuracy predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750											-9.142	Likely Pathogenic	0.694	Likely Pathogenic	Likely Benign	6.54	Destabilizing	8.5	4.79	Destabilizing	5.67	Destabilizing	0.31	Likely Benign	0.606	Likely Pathogenic	-0.74	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			0.1296	0.4417		-3	-2	-4.1	99.14
c.1163G>A	G388D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G388D is reported in gnomAD (variant ID 6-33438068‑G‑A) but has no entry in ClinVar. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions arise from SGM‑Consensus, REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments reinforce this split: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic; Foldetta, integrating FoldX‑MD and Rosetta outputs, also predicts a pathogenic impact on protein stability. Taken together, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect for G388D, 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	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750								6-33438068-G-A			-8.416	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	5.56	Destabilizing	7.3	3.08	Destabilizing	4.32	Destabilizing	0.42	Likely Benign	0.618	Likely Pathogenic	-0.67	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	3	0.1923	0.1624		-1	1	-3.1	58.04
c.1163G>T	G388V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G388V is catalogued in gnomAD (6-33438068-G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates benign, whereas Foldetta—combining FoldX‑MD and Rosetta stability outputs—labels the variant as pathogenic. Overall, the majority of tools and the Foldetta result point to a pathogenic effect. This conclusion does not conflict with ClinVar, which currently contains no classification for G388V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750								6-33438068-G-T			-6.887	Likely Benign	0.120	Likely Benign	Likely Benign	6.58	Destabilizing	6.6	5.51	Destabilizing	6.05	Destabilizing	-0.11	Likely Benign	0.620	Likely Pathogenic	-0.93	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.01	Affected	4.32	3	0.1600	0.3897		-3	-1	4.6	42.08
c.1172G>T	G391V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G391V is listed in ClinVar as Benign (ClinVar ID 1014488.0) and is present in gnomAD (variant ID 6‑33438077‑G‑T). Prediction tools that classify the variant as benign include premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. Tools that predict pathogenicity are REVEL, FoldX, Rosetta, Foldetta, 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) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. With two high‑accuracy tools supporting benign and one supporting pathogenic, the overall prediction leans toward a benign effect. This conclusion aligns with the ClinVar benign classification, so there is no contradiction with the existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.637480	Disordered	0.409509	Uncertain	0.279	0.741	0.750					Likely Benign		1	6-33438077-G-T	3	1.86e-6	-6.642	Likely Benign	0.133	Likely Benign	Likely Benign	4.23	Destabilizing	1.3	4.81	Destabilizing	4.52	Destabilizing	-0.11	Likely Benign	0.595	Likely Pathogenic	-0.98	Neutral	0.994	Probably Damaging	0.887	Possibly Damaging	1.32	Pathogenic	0.10	Tolerated	3.69	8	0.1621	0.3821		-1	-3	4.6	42.08	228.6	-69.0	0.0	0.8	-0.5	0.3								Uncertain	Gly387 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364 and res. Ala399-Ile411). The Ω loop is assumed to directly interact with the membrane, and it is observed to move arbitrarily throughout the WT solvent simulations. This loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play significant roles in protein functions that require flexibility, and thus hydrophobic residues like valine are rarely tolerated. Although no negative structural effects are visualized in the variant’s simulations, Val391 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. Since the effects on the Gly-rich Ω loop dynamics can only be well studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.1204C>A	L402M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402M is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain 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 likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-6.991	Likely Benign	0.305	Likely Benign	Likely Benign	0.12	Likely Benign	0.0	1.33	Ambiguous	0.73	Ambiguous	0.80	Ambiguous	0.071	Likely Benign	-0.99	Neutral	0.994	Probably Damaging	0.938	Probably Damaging	3.73	Benign	0.02	Affected			0.1064	0.4095		4	2	-1.9	18.03
c.1253A>G	K418R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Optimized. Tools that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus methods give a benign verdict: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign (3 benign vs. 1 pathogenic); and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. premPS is uncertain and therefore not considered evidence. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-6.809	Likely Benign	0.635	Likely Pathogenic	Likely Benign	-0.18	Likely Benign	0.1	0.12	Likely Benign	-0.03	Likely Benign	0.56	Ambiguous	0.229	Likely Benign	-2.46	Neutral	0.994	Probably Damaging	0.962	Probably Damaging	3.37	Benign	0.04	Affected			0.4384	0.1151		3	2	-0.6	28.01
c.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.1298C>T	A433V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A433V missense variant is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438203‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore unavailable as evidence. Overall, the majority of predictions support a benign impact, and this is consistent with the lack of ClinVar pathogenic classification. Thus, the variant is most likely benign based on current computational evidence, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000								6-33438203-C-T	240	1.49e-4	-8.200	Likely Pathogenic	0.129	Likely Benign	Likely Benign	0.48	Likely Benign	0.1	-0.07	Likely Benign	0.21	Likely Benign	0.48	Likely Benign	0.096	Likely Benign	-2.91	Deleterious	0.994	Probably Damaging	0.527	Possibly Damaging	3.43	Benign	0.04	Affected	3.37	29	0.0753	0.5104		0	0	2.4	28.05	214.5	-45.8	0.0	0.0	0.0	0.2						X		Potentially Benign	The methyl group of Ala433, located on the outer surface of an α helix (res. Met414-Glu436), does not interact with any nearby residues in the WT simulations. In the variant simulations, the iso-propyl side chain of Val433, which has a similarly hydrophobic profile as alanine, also does not form any lasting interactions at the helix surface. Accordingly, the residue swap does not negatively affect the protein structure based on the simulations.
c.1306G>A	E436K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining evaluated algorithms (REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a pathogenic impact; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E436K, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000					Uncertain		1				-13.869	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.56	Ambiguous	0.1	2.86	Destabilizing	1.71	Ambiguous	0.82	Ambiguous	0.829	Likely Pathogenic	-3.77	Deleterious	0.994	Probably Damaging	0.951	Probably Damaging	4.71	Benign	0.02	Affected	3.37	29	0.2332	0.5995		0	1	-0.4	-0.94	186.8	39.8	0.0	0.0	-0.2	0.0	X	X		X				Potentially Pathogenic	The carboxylate group of Glu436, located on the α helix (res. Met414-Glu436), forms a salt bridge with the amino group of the Lys444 side chain on an opposing α helix (res. Val441-Ser457). The backbone carbonyl of Glu436 also H-bonds with the Lys444 side chain, which helps keep the ends of the two α helices tightly connected. In contrast, in the variant simulations, the salt bridge formation with Lys444 is not possible. Instead, the repelled Lys436 side chain rotates outward, causing a change in the α helix backbone H-bonding: the amide group of Lys444 H-bonds with the carbonyl of Ala433 instead of the carbonyl of Cys432.
c.1336G>A	E446K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446K is not reported in ClinVar (ClinVar status: not present) and is found in gnomAD (ID 6‑33438241‑G‑A). Prediction tools that agree on a benign effect include only FATHMM. Tools that agree on a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy methods give the following: AlphaMissense‑Optimized is uncertain; SGM‑Consensus indicates likely pathogenic; Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000								6-33438241-G-A	1	6.19e-7	-14.140	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.4	1.57	Ambiguous	1.19	Ambiguous	0.81	Ambiguous	0.518	Likely Pathogenic	-3.75	Deleterious	0.994	Probably Damaging	0.975	Probably Damaging	3.36	Benign	0.01	Affected	3.38	31	0.2141	0.6511		1	0	-0.4	-0.94
c.1388A>G	D463G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463G missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Five tools favor pathogenicity versus three favor benign, with the remaining five (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) yielding uncertain results. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, also remains inconclusive. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-10.713	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous	0.66	Ambiguous	0.1	1.93	Ambiguous	1.30	Ambiguous	0.54	Ambiguous	0.422	Likely Benign	-6.36	Deleterious	0.994	Probably Damaging	0.824	Possibly Damaging	3.32	Benign	0.09	Tolerated			0.3751	0.4898		1	-1	3.1	-58.04
c.139C>T	R47W 2D AIThe SynGAP1 missense variant R47W is listed in ClinVar as a variant of uncertain significance and is present in the gnomAD database (ID 6‑33423548‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes), and Foldetta results are unavailable. Overall, the majority of conventional tools suggest a pathogenic impact, but the single high‑accuracy benign prediction and the inconclusive consensus temper this view. Consequently, the variant is most likely pathogenic based on the preponderance of evidence, and this assessment does not contradict the ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125					Uncertain		1	6-33423548-C-T	1	6.20e-7	-9.201	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-2.17	Neutral	0.994	Probably Damaging	0.919	Probably Damaging	4.00	Benign	0.00	Affected	4.32	1	0.1101	0.4158		-3	2	3.6	30.03
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.1405G>A	A469T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A469T 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 premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and the Foldetta stability assessment (combining FoldX‑MD and Rosetta). The high‑accuracy subset shows AlphaMissense‑Optimized as benign, whereas SGM Consensus and Foldetta both predict pathogenic. Overall, the majority of evidence supports a pathogenic effect, and this conclusion 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	0.278302	Structured	0.343926	Uncertain	0.910	0.276	0.000					Uncertain		1				-9.540	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	2.26	Destabilizing	0.1	1.90	Ambiguous	2.08	Destabilizing	0.34	Likely Benign	0.527	Likely Pathogenic	-1.46	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	-1.21	Pathogenic	0.42	Tolerated			0.1005	0.5884		1	0	-2.5	30.03
c.1414G>C	E472Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472Q is 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 Foldetta, which classifies the variant as benign. Tools that predict a pathogenic effect are 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). Uncertain or inconclusive predictions come from FoldX, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact for E472Q, 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											-13.760	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	1.34	Ambiguous	0.3	-0.67	Ambiguous	0.34	Likely Benign	0.89	Ambiguous	0.555	Likely Pathogenic	-2.95	Deleterious	0.994	Probably Damaging	0.986	Probably Damaging	2.39	Pathogenic	0.01	Affected			0.1388	0.5726		2	2	0.0	-0.98
c.1438G>C	E480Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 E480Q is not reported in ClinVar (no ClinVar ID) and is present in gnomAD (ID 6‑33438470‑G‑C). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, and the protein‑folding stability method Foldetta. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized is uncertain and therefore not used as evidence. High‑accuracy assessments show Foldetta predicts benign stability change, SGM Consensus predicts pathogenic, and AlphaMissense‑Optimized is inconclusive. Overall, the predictions are split, but the presence of a benign prediction from a high‑accuracy folding method and the lack of a ClinVar pathogenic claim suggest the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000								6-33438470-G-C	2	1.24e-6	-12.336	Likely Pathogenic	0.845	Likely Pathogenic	Ambiguous	0.43	Likely Benign	0.0	-0.01	Likely Benign	0.21	Likely Benign	0.75	Ambiguous	0.480	Likely Benign	-2.29	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	-1.29	Pathogenic	0.11	Tolerated	3.37	34	0.0854	0.6870		2	2	0.0	-0.98
c.1444C>A	L482I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from PROVEAN and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (REVEL, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) indicate pathogenicity. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments give a consistent picture: AlphaMissense‑Optimized predicts a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain outcome. Overall, the preponderance of pathogenic predictions suggests that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.116	Likely Pathogenic	0.760	Likely Pathogenic	Likely Benign	1.29	Ambiguous	0.1	1.90	Ambiguous	1.60	Ambiguous	0.71	Ambiguous	0.600	Likely Pathogenic	-1.97	Neutral	0.994	Probably Damaging	0.994	Probably Damaging	-1.31	Pathogenic	0.05	Affected			0.0677	0.2368		2	2	0.7	0.00
c.1458G>C	E486D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E486D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools are uncertain (premPS, AlphaMissense‑Optimized). High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Because the majority of standard predictors lean toward pathogenic and the SGM‑Consensus also indicates pathogenic, the variant is most likely pathogenic, although the Foldetta benign prediction and the presence of uncertain calls leave room for ambiguity. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.363	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	0.38	Likely Benign	0.29	Likely Benign	0.54	Ambiguous	0.166	Likely Benign	-2.58	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	3.43	Benign	0.16	Tolerated			0.1453	0.4115		3	2	0.0	-14.03
c.1458G>T	E486D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E486D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls (REVEL, FoldX, Rosetta, SIFT, FATHMM) and pathogenic calls (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools are uncertain (premPS, AlphaMissense‑Optimized). High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Because the majority of standard predictors lean toward pathogenic and the SGM‑Consensus also indicates pathogenic, the variant is most likely pathogenic, although the Foldetta benign prediction and the presence of uncertain calls leave room for ambiguity. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.363	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	0.38	Likely Benign	0.29	Likely Benign	0.54	Ambiguous	0.166	Likely Benign	-2.58	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	3.43	Benign	0.16	Tolerated			0.1453	0.4115		3	2	0.0	-14.03
c.1555G>C	E519Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect on protein stability. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.693	Likely Pathogenic	0.792	Likely Pathogenic	Ambiguous	-0.35	Likely Benign	0.1	-0.14	Likely Benign	-0.25	Likely Benign	-0.21	Likely Benign	0.195	Likely Benign	-2.48	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	3.28	Benign	0.14	Tolerated			0.1394	0.3418		2	2	0.0	-0.98
c.1561G>A	E521K 2D 3DClick to see structure in 3D Viewer AISynGAP1 E521K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. Overall, the majority of conventional tools lean toward a benign interpretation, while the high‑accuracy methods are split. Thus, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-9.596	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	-0.48	Likely Benign	0.2	0.14	Likely Benign	-0.17	Likely Benign	-0.10	Likely Benign	0.379	Likely Benign	-3.05	Deleterious	0.994	Probably Damaging	0.994	Probably Damaging	3.57	Benign	0.45	Tolerated			0.2895	0.6513		0	1	-0.4	-0.94
c.1564G>A	E522K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E522K has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, both polyPhen‑2 versions, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further indicate AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus also predicts Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts Benign. No prediction is available from FoldX (Uncertain). Overall, the majority of high‑confidence tools lean toward pathogenicity, 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	0.092881	Structured	0.046216	Uncertain	0.823	0.376	0.000											-12.637	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	-0.69	Ambiguous	0.1	0.14	Likely Benign	-0.28	Likely Benign	-0.13	Likely Benign	0.631	Likely Pathogenic	-3.81	Deleterious	0.994	Probably Damaging	0.994	Probably Damaging	-1.09	Pathogenic	0.23	Tolerated			0.2019	0.4291		0	1	-0.4	-0.94
c.157G>A	G53R 2D AIThe SynGAP1 missense variant G53R is not 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. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic + 2 benign), and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic impact. Because there is no ClinVar entry to contradict this assessment, 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.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.400	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.20	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.13	Benign	0.00	Affected			0.0953	0.4347		-3	-2	-4.1	99.14
c.157G>C	G53R 2D AIThe SynGAP1 missense variant G53R is not 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. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic + 2 benign), and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of tools (5 pathogenic vs. 3 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 has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.400	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.20	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.13	Benign	0.00	Affected			0.0953	0.4347		-3	-2	-4.1	99.14
c.158G>A	G53E 2D AIThe SynGAP1 missense variant G53E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-2.061	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.198	Likely Benign	-0.25	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	4.29	Benign	0.00	Affected			0.1413	0.4378		0	-2	-3.1	72.06
c.158G>T	G53V 2D AIThe SynGAP1 missense variant G53V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.308	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.238	Likely Benign	-1.71	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.11	Benign	0.00	Affected			0.1193	0.4833		-1	-3	4.6	42.08
c.1619A>T	Q540L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540L has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX is uncertain and therefore not considered. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for Q540L, 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	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000											-14.266	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	-0.71	Ambiguous	0.1	0.44	Likely Benign	-0.14	Likely Benign	0.50	Likely Benign	0.756	Likely Pathogenic	-6.96	Deleterious	0.994	Probably Damaging	0.977	Probably Damaging	-1.06	Pathogenic	0.08	Tolerated			0.0654	0.3601		-2	-2	7.3	-14.97
c.1660G>A	V554M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V554M is not reported in ClinVar but is present in gnomAD (ID 6‑33438903‑G‑A). Functional prediction tools show a split opinion: benign calls come from REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessment focuses on AlphaMissense‑Optimized, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. AlphaMissense‑Optimized predicts benign, the SGM Consensus is a tie and thus unavailable, and Foldetta is uncertain, so it is treated as unavailable. Overall, the available evidence leans toward a benign effect, and this 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.		GAP	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000								6-33438903-G-A	1	6.20e-7	-8.118	Likely Pathogenic	0.671	Likely Pathogenic	Likely Benign	-1.11	Ambiguous	0.0	-0.20	Likely Benign	-0.66	Ambiguous	0.73	Ambiguous	0.217	Likely Benign	-2.26	Neutral	0.994	Probably Damaging	0.867	Possibly Damaging	3.22	Benign	0.00	Affected	3.37	35	0.0743	0.2810		1	2	-2.3	32.06
c.1692G>C	E564D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT, whereas a majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-10.184	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	1.13	Ambiguous	0.80	Ambiguous	0.26	Likely Benign	0.637	Likely Pathogenic	-2.75	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.1431	0.3354		3	2	0.0	-14.03
c.1692G>T	E564D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and SIFT, whereas a majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000											-10.184	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous	0.47	Likely Benign	0.1	1.13	Ambiguous	0.80	Ambiguous	0.26	Likely Benign	0.637	Likely Pathogenic	-2.75	Deleterious	0.994	Probably Damaging	0.979	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.1431	0.3354		3	2	0.0	-14.03
c.1732G>C	E578Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E578Q missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors indicates a benign effect: REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, AlphaMissense‑Optimized, and Foldetta all predict benign. Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic. Foldetta, a protein‑folding stability method, also predicts benign. Overall, the majority of tools, including the high‑accuracy AlphaMissense‑Optimized and Foldetta, support a benign classification, and this is consistent with the lack of ClinVar evidence. 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.		GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000											-9.771	Likely Pathogenic	0.491	Ambiguous	Likely Benign	0.01	Likely Benign	0.1	-0.12	Likely Benign	-0.06	Likely Benign	-0.16	Likely Benign	0.353	Likely Benign	-1.21	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	-1.40	Pathogenic	0.36	Tolerated			0.1000	0.5319		2	2	0.0	-0.98
c.1744G>A	E582K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E582K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect on protein stability. Taken together, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-11.826	Likely Pathogenic	0.814	Likely Pathogenic	Ambiguous	0.20	Likely Benign	0.1	0.07	Likely Benign	0.14	Likely Benign	0.02	Likely Benign	0.168	Likely Benign	-1.83	Neutral	0.994	Probably Damaging	0.994	Probably Damaging	3.31	Benign	0.33	Tolerated			0.2038	0.3762		0	1	-0.4	-0.94
c.1837G>C	E613Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E613Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and SIFT, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the balance of evidence leans toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-9.245	Likely Pathogenic	0.887	Likely Pathogenic	Ambiguous	0.41	Likely Benign	0.4	-0.84	Ambiguous	-0.22	Likely Benign	0.11	Likely Benign	0.495	Likely Benign	-2.79	Deleterious	0.994	Probably Damaging	0.986	Probably Damaging	-1.28	Pathogenic	0.09	Tolerated			0.1650	0.6181		2	2	0.0	-0.98
c.1851G>C	E617D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E617D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports a benign effect. Based on the preponderance of evidence from both general and high‑accuracy predictors, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000											-1.349	Likely Benign	0.241	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	0.322	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	0.1854	0.3386		2	3	0.0	-14.03
c.1851G>T	E617D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617D is listed in ClinVar with an uncertain significance (ID 2584916.0) and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all indicate benign or likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact, while Rosetta remains inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Overall, the preponderance of evidence supports a benign classification, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000					Uncertain		1				-1.349	Likely Benign	0.241	Likely Benign	Likely Benign	0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	0.322	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	0.1854	0.3386		2	3	0.0	-14.03
c.1879G>A	A627T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A627T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. Two tools, premPS and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict, and Foldetta also predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains uncertain. Overall, the preponderance of evidence indicates that A627T is most likely pathogenic, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.037862	Uncertain	0.970	0.210	0.000											-8.613	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous	2.27	Destabilizing	0.3	2.33	Destabilizing	2.30	Destabilizing	0.80	Ambiguous	0.505	Likely Pathogenic	-3.95	Deleterious	0.994	Probably Damaging	0.807	Possibly Damaging	2.56	Benign	0.01	Affected			0.1069	0.5403		1	0	-2.5	30.03
c.1900G>A	A634T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634T is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, while only FATHMM predicts benign. Two tools give uncertain results: AlphaMissense‑Optimized and Foldetta. High‑accuracy assessment shows that the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) supports a pathogenic classification, whereas AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for A634T, 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	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-12.451	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.56	Destabilizing	0.1	1.11	Ambiguous	1.84	Ambiguous	1.34	Destabilizing	0.603	Likely Pathogenic	-3.98	Deleterious	0.994	Probably Damaging	0.986	Probably Damaging	2.51	Benign	0.01	Affected			0.1397	0.5240		1	0	-2.5	30.03
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.1937T>A	L646Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L646Q lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect are REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Taken together, the overwhelming majority of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000											-12.735	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign	3.23	Destabilizing	0.1	3.04	Destabilizing	3.14	Destabilizing	2.12	Destabilizing	0.462	Likely Benign	-2.78	Deleterious	0.994	Probably Damaging	0.790	Possibly Damaging	3.17	Benign	0.00	Affected			0.2090	0.1963		-2	-2	-7.3	14.97
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.2095G>A	V699M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V699M is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441354‑G‑A). Across in silico predictors, benign calls are made by REVEL, Rosetta, Foldetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Predictions that are inconclusive (FoldX, premPS, AlphaMissense‑Default) are noted but not used as evidence. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports benign stability. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the ClinVar uncertain status but provides a stronger leaning toward benignity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000					Uncertain		2	6-33441354-G-A	8	4.96e-6	-8.869	Likely Pathogenic	0.484	Ambiguous	Likely Benign	-0.58	Ambiguous	0.1	0.29	Likely Benign	-0.15	Likely Benign	0.96	Ambiguous	0.276	Likely Benign	-2.18	Neutral	0.994	Probably Damaging	0.806	Possibly Damaging	3.37	Benign	0.03	Affected	3.47	10	0.0734	0.3071		2	1	-2.3	32.06	257.8	-47.2	0.0	0.0	0.9	0.1						X		Potentially Benign	The isopropyl side chain of Val699, located on an α-helix (res. Leu685-Gln702), packs against hydrophobic residues (e.g., Leu703, Leu696, Leu435, Leu439) in the inter-helix space. In the variant simulations, the thioether side chain of Met699 has similar physicochemical properties to Val699 in the WT, and thus, it is able to maintain similar interactions. Consequently, the mutation causes no apparent changes in the structure.
c.2099T>A	L700Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700Q is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized indicates a benign change, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both predict pathogenicity. No predictions are missing or inconclusive. Overall, the preponderance of evidence from the majority of tools points to a pathogenic effect, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-10.522	Likely Pathogenic	0.783	Likely Pathogenic	Likely Benign	2.41	Destabilizing	0.1	4.02	Destabilizing	3.22	Destabilizing	1.35	Destabilizing	0.321	Likely Benign	-3.79	Deleterious	0.994	Probably Damaging	0.896	Possibly Damaging	3.34	Benign	0.01	Affected			0.1074	0.0488		-2	-2	-7.3	14.97
c.2107C>T	L703F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized, while those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta remains unavailable. Overall, the majority of reliable predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.929	Likely Pathogenic	0.768	Likely Pathogenic	Likely Benign	1.03	Ambiguous	0.1	0.59	Ambiguous	0.81	Ambiguous	0.50	Likely Benign	0.247	Likely Benign	-3.25	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.12	Benign	0.00	Affected			0.0600	0.2555		2	0	-1.0	34.02
c.2108T>G	L703R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) all classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. The preponderance of pathogenic predictions, together with the high‑accuracy tools’ positive results, suggests that L703R is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-13.244	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	2.85	Destabilizing	0.0	3.74	Destabilizing	3.30	Destabilizing	1.79	Destabilizing	0.459	Likely Benign	-4.92	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.13	Benign	0.00	Affected			0.1223	0.0488		-3	-2	-8.3	43.03
c.214C>T	R72W 2D AIThe SynGAP1 missense variant R72W is catalogued in gnomAD (ID 6‑33425822‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by 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 also indicates a likely benign outcome. The Foldetta stability analysis is unavailable, providing no additional evidence. Overall, the preponderance of computational evidence points to a benign effect for R72W, 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		0.497853	Structured	0.455349	Uncertain	0.355	0.819	0.375								6-33425822-C-T	1	6.20e-7	-5.546	Likely Benign	0.430	Ambiguous	Likely Benign										0.145	Likely Benign	-1.82	Neutral	0.994	Probably Damaging	0.689	Possibly Damaging	4.07	Benign	0.00	Affected	4.32	1	0.1601	0.3652		-3	2	3.6	30.03
c.2267A>G	Q756R 2D AIThe SynGAP1 missense variant Q756R is 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. 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 for Q756R, 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		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-5.044	Likely Benign	0.307	Likely Benign	Likely Benign										0.245	Likely Benign	-1.77	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	1.58	Pathogenic	0.14	Tolerated			0.1500	0.2440		1	1	-1.0	28.06
c.2267A>T	Q756L 2D AIThe SynGAP1 missense variant Q756L is 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is labeled “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. 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 for Q756L, 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		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-3.697	Likely Benign	0.339	Likely Benign	Likely Benign										0.274	Likely Benign	-1.95	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	1.56	Pathogenic	0.08	Tolerated			0.0797	0.5700		-2	-2	7.3	-14.97
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.2286C>A	D762E 2D AIThe SynGAP1 D762E 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, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-4.332	Likely Benign	0.459	Ambiguous	Likely Benign										0.144	Likely Benign	-1.59	Neutral	0.994	Probably Damaging	0.891	Possibly Damaging	2.18	Pathogenic	0.05	Affected			0.1911	0.8236		3	2	0.0	14.03
c.2286C>G	D762E 2D AIThe SynGAP1 D762E 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, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-4.332	Likely Benign	0.459	Ambiguous	Likely Benign										0.144	Likely Benign	-1.59	Neutral	0.994	Probably Damaging	0.891	Possibly Damaging	2.18	Pathogenic	0.05	Affected			0.1911	0.8236		3	2	0.0	14.03
c.2398G>T	G800C 2D AIThe SynGAP1 missense variant G800C is not reported in ClinVar and has no allele in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a benign outcome; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of a ClinVar pathogenic annotation. Based on the aggregate predictions, the variant is most likely benign, and this is consistent with the lack of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.852992	Disordered	0.588350	Binding	0.303	0.884	0.625											-7.074	In-Between	0.129	Likely Benign	Likely Benign										0.144	Likely Benign	-1.53	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	2.70	Benign	0.15	Tolerated			0.1102	0.4189		-3	-3	2.9	46.09
c.2434C>A	P812T 2D AIThe SynGAP1 missense variant P812T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict 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 further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates 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). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.956	Likely Benign	0.524	Ambiguous	Likely Benign										0.105	Likely Benign	-1.50	Neutral	0.994	Probably Damaging	0.927	Probably Damaging	2.73	Benign	0.04	Affected			0.1413	0.6114		0	-1	0.9	3.99
c.2437C>G	L813V 2D AIThe SynGAP1 missense variant L813V 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 the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized 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 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	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-4.809	Likely Benign	0.215	Likely Benign	Likely Benign										0.136	Likely Benign	-0.98	Neutral	0.994	Probably Damaging	0.856	Possibly Damaging	2.62	Benign	0.28	Tolerated			0.1704	0.3744		2	1	0.4	-14.03
c.2452C>A	P818T 2D AIThe SynGAP1 missense variant P818T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.864	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.265	Likely Benign	-4.58	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.01	Pathogenic	0.02	Affected			0.1797	0.6453		0	-1	0.9	3.99
c.2455G>T	A819S 2D AIThe SynGAP1 missense variant A819S is 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, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. 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 A819S, 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		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-3.420	Likely Benign	0.331	Likely Benign	Likely Benign										0.199	Likely Benign	-1.49	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	2.33	Pathogenic	0.27	Tolerated			0.2729	0.6404		1	1	-2.6	16.00
c.2485G>A	E829K 2D AIThe SynGAP1 missense variant E829K is listed in ClinVar as Pathogenic (ClinVar ID 1721258.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only REVEL predicts a benign outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E829K is most likely pathogenic, and this conclusion aligns with the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375					Pathogenic		1				-7.527	In-Between	0.807	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-2.65	Deleterious	0.994	Probably Damaging	0.900	Possibly Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.2400	0.7372		0	1	-0.4	-0.94
c.2485G>C	E829Q 2D AIThe SynGAP1 missense variant E829Q is not 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, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields 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 reliable tools predict a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.985	Likely Benign	0.531	Ambiguous	Likely Benign										0.225	Likely Benign	-1.83	Neutral	0.994	Probably Damaging	0.946	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1321	0.7248		2	2	0.0	-0.98
c.2486A>C	E829A 2D AIThe SynGAP1 missense variant E829A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Overall, the majority of evidence—including the SGM‑Consensus—points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.096	Likely Benign	0.574	Likely Pathogenic	Likely Benign										0.265	Likely Benign	-3.75	Deleterious	0.994	Probably Damaging	0.926	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.4707	0.7255		0	-1	5.3	-58.04
c.2486A>G	E829G 2D AIThe SynGAP1 missense variant E829G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward pathogenicity, with one high‑accuracy tool suggesting benign. No ClinVar annotation exists, so there is no contradiction with clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.152	Likely Benign	0.593	Likely Pathogenic	Likely Benign										0.316	Likely Benign	-4.52	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.3517	0.6557		0	-2	3.1	-72.06
c.2600G>A	G867E 2D AIThe SynGAP1 missense variant G867E is catalogued in gnomAD (6‑33443152‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by polyPhen‑2 HumDiv and polyPhen‑2 HumVar, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus 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 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		0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250								6-33443152-G-A	3	1.86e-6	-5.204	Likely Benign	0.492	Ambiguous	Likely Benign										0.105	Likely Benign	-1.57	Neutral	0.994	Probably Damaging	0.943	Probably Damaging	2.74	Benign	0.07	Tolerated	3.82	4	0.1305	0.3880		-2	0	-3.1	72.06
c.2734A>T	T912S 2D AIThe SynGAP1 missense variant T912S 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. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for T912S, 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		0.724957	Disordered	0.740671	Binding	0.285	0.909	0.250											-2.647	Likely Benign	0.127	Likely Benign	Likely Benign										0.074	Likely Benign	-1.05	Neutral	0.994	Probably Damaging	0.856	Possibly Damaging	4.18	Benign	0.00	Affected			0.3078	0.3893		1	1	-0.1	-14.03
c.2735C>G	T912S 2D AIThe SynGAP1 missense variant T912S 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. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for T912S, 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		0.724957	Disordered	0.740671	Binding	0.285	0.909	0.250											-2.647	Likely Benign	0.127	Likely Benign	Likely Benign										0.128	Likely Benign	-1.05	Neutral	0.994	Probably Damaging	0.856	Possibly Damaging	4.18	Benign	0.00	Affected			0.3078	0.3893		1	1	-0.1	-14.03
c.2762T>A	L921Q 2D AIThe SynGAP1 missense variant L921Q is 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, 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		0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375											-2.389	Likely Benign	0.311	Likely Benign	Likely Benign										0.132	Likely Benign	-0.62	Neutral	0.994	Probably Damaging	0.940	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1097	0.1119		-2	-2	-7.3	14.97
c.2762T>G	L921R 2D AIThe SynGAP1 missense variant L921R is not 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 agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375											-2.205	Likely Benign	0.563	Ambiguous	Likely Benign										0.217	Likely Benign	-1.19	Neutral	0.994	Probably Damaging	0.912	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1306	0.0761		-3	-2	-8.3	43.03
c.2783A>G	Q928R 2D AIThe SynGAP1 missense variant Q928R is listed in gnomAD (ID 6‑33443335‑A‑G) but has no ClinVar entry. Functional prediction tools fall into two consensus groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta stability) data are available. High‑accuracy assessments therefore indicate a likely pathogenic outcome (SGM‑Consensus) with no contradictory evidence from ClinVar. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250								6-33443335-A-G	1	6.20e-7	-4.089	Likely Benign	0.826	Likely Pathogenic	Ambiguous										0.290	Likely Benign	-2.91	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.58	Pathogenic	0.00	Affected	4.32	4	0.1357	0.3453		1	1	-1.0	28.06
c.2783A>T	Q928L 2D AIThe SynGAP1 missense variant Q928L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250											-6.237	Likely Benign	0.919	Likely Pathogenic	Ambiguous										0.373	Likely Benign	-4.57	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.0757	0.6091		-2	-2	7.3	-14.97
c.2900G>A	R967Q 2D AIThe SynGAP1 missense variant R967Q is listed in ClinVar as Benign (ClinVar ID 536992.0) and is present in gnomAD (6‑33443452‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; 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		0.974374	Disordered	0.969686	Binding	0.340	0.888	0.750					Benign/Likely benign		2	6-33443452-G-A	31	1.92e-5	-3.057	Likely Benign	0.080	Likely Benign	Likely Benign										0.104	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.626	Possibly Damaging	4.21	Benign	0.36	Tolerated	4.32	2	0.3141	0.3446		1	1	1.0	-28.06
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.299A>G	Y100C 2D AIThe SynGAP1 missense variant Y100C 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 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		0.699094	Disordered	0.675421	Binding	0.341	0.880	0.625											-3.789	Likely Benign	0.117	Likely Benign	Likely Benign										0.172	Likely Benign	-0.88	Neutral	0.994	Probably Damaging	0.816	Possibly Damaging	4.18	Benign	0.00	Affected			0.3073	0.2213		0	-2	3.8	-60.04
c.3029T>C	F1010S 2D AIThe SynGAP1 missense variant F1010S is listed in gnomAD (ID 6‑33443581‑T‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome 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 benign; Foldetta results are unavailable. Overall, the balance of evidence, including the high‑accuracy benign predictions and the consensus benign call, indicates that the variant is most likely benign. 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		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625								6-33443581-T-C			-1.722	Likely Benign	0.744	Likely Pathogenic	Likely Benign										0.153	Likely Benign	-1.97	Neutral	0.994	Probably Damaging	0.892	Possibly Damaging	2.51	Benign	0.01	Affected	3.77	5	0.4196	0.0775		-2	-3	-3.6	-60.10
c.3046G>C	D1016H 2D AIThe SynGAP1 D1016H missense variant is catalogued in gnomAD (ID 6‑33443598‑G‑C) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a deleterious effect. Consequently, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625								6-33443598-G-C			-3.398	Likely Benign	0.792	Likely Pathogenic	Ambiguous										0.259	Likely Benign	-2.63	Deleterious	0.994	Probably Damaging	0.924	Probably Damaging	2.45	Pathogenic	0.00	Affected	3.77	5	0.2348	0.7744		-1	1	0.3	22.05
c.3070C>T	L1024F 2D AIThe SynGAP1 missense variant L1024F is not 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, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it contains both benign and pathogenic calls. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence favors a benign 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.			0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-5.133	Likely Benign	0.544	Ambiguous	Likely Benign										0.059	Likely Benign	-2.08	Neutral	0.994	Probably Damaging	0.924	Probably Damaging	2.40	Pathogenic	0.07	Tolerated			0.0706	0.3708		2	0	-1.0	34.02
c.3166G>T	G1056C 2D AIThe SynGAP1 missense variant G1056C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988291	Disordered	0.868632	Binding	0.402	0.935	0.875											-9.974	Likely Pathogenic	0.122	Likely Benign	Likely Benign										0.432	Likely Benign	-0.70	Neutral	0.994	Probably Damaging	0.777	Possibly Damaging	1.83	Pathogenic	0.06	Tolerated			0.1414	0.4439		-3	-3	2.9	46.09
c.3203T>G	L1068W 2D AIThe SynGAP1 missense variant L1068W 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, PROVEAN, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all predict a pathogenic outcome; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized remains benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves as pathogenic, and Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact for L1068W. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.947281	Disordered	0.981041	Binding	0.362	0.907	0.875											-8.574	Likely Pathogenic	0.342	Ambiguous	Likely Benign										0.151	Likely Benign	-1.96	Neutral	0.994	Probably Damaging	0.884	Possibly Damaging	2.46	Pathogenic	0.00	Affected			0.0742	0.3763		-2	-2	-4.7	73.05
c.3349G>T	G1117C 2D AIThe SynGAP1 missense variant G1117C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The 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. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750											-9.045	Likely Pathogenic	0.112	Likely Benign	Likely Benign										0.359	Likely Benign	-1.30	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	4.56	Benign	0.03	Affected			0.1347	0.4612		-3	-3	2.9	46.09
c.3358G>T	G1120C 2D AIThe SynGAP1 missense variant G1120C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability result is available. Overall, the majority of evidence points to a benign impact for G1120C, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875											-9.324	Likely Pathogenic	0.112	Likely Benign	Likely Benign										0.311	Likely Benign	-1.32	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	3.60	Benign	0.03	Affected			0.1271	0.4227		-3	-3	2.9	46.09
c.3361A>T	S1121C 2D AIThe SynGAP1 missense variant S1121C is listed in gnomAD (ID 6‑33443913‑A‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, 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, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while the 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		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875								6-33443913-A-T			-7.431	In-Between	0.094	Likely Benign	Likely Benign										0.354	Likely Benign	-0.99	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	5.43	Benign	0.00	Affected	3.77	5	0.1705	0.5691		-1	0	3.3	16.06
c.3367G>T	G1123C 2D AIThe SynGAP1 missense variant G1123C is listed in gnomAD (ID 6‑33443919‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy tools—supports a benign classification. 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.	Likely Benign		0.837511	Disordered	0.827246	Binding	0.346	0.934	0.875								6-33443919-G-T	1	6.64e-7	-9.329	Likely Pathogenic	0.118	Likely Benign	Likely Benign										0.353	Likely Benign	-1.17	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	4.34	Benign	0.10	Tolerated	3.77	5	0.1348	0.4227		-3	-3	2.9	46.09
c.3588G>C	K1196N 2D AIThe SynGAP1 missense variant K1196N is 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 and HumVar), SIFT, 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus indicates benignity; a Foldetta stability analysis is unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.3588G>T	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further divide the evidence: AlphaMissense‑Optimized predicts a pathogenic effect, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. With no ClinVar classification to resolve the conflict, the overall computational signal is inconclusive, but the presence of a pathogenic prediction from a high‑accuracy model and the absence of a benign consensus suggest the variant is more likely pathogenic. This assessment does not contradict any ClinVar status, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.3598G>A	E1200K 2D AIThe SynGAP1 missense variant E1200K is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and 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 Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign effect, with no conflict with ClinVar status (which has no entry). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-6.489	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.158	Likely Benign	-1.05	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	2.71	Benign	0.19	Tolerated			0.1690	0.4551		0	1	-0.4	-0.94
c.3598G>C	E1200Q 2D AIThe SynGAP1 missense variant E1200Q 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, 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) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available, so these do not influence the overall interpretation. High‑accuracy assessments—AlphaMissense‑Optimized (benign) and SGM‑Consensus (likely benign)—support a benign classification. Consequently, the variant is most likely benign, 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	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-4.411	Likely Benign	0.464	Ambiguous	Likely Benign										0.183	Likely Benign	0.14	Neutral	0.994	Probably Damaging	0.946	Probably Damaging	2.84	Benign	0.30	Tolerated			0.0767	0.4012		2	2	0.0	-0.98
c.3599A>C	E1200A 2D AIThe SynGAP1 E1200A 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, polyPhen‑2 HumVar, and SIFT. The high‑accuracy AlphaMissense‑Optimized score is benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (benign), FATHMM (benign), and PROVEAN (pathogenic), is benign. Foldetta results are unavailable. Overall, the balance of evidence (five benign versus four pathogenic predictions, with a benign SGM Consensus and high‑accuracy benign AlphaMissense‑Optimized) indicates that the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-3.115	Likely Benign	0.505	Ambiguous	Likely Benign										0.220	Likely Benign	-2.61	Deleterious	0.994	Probably Damaging	0.926	Probably Damaging	2.72	Benign	0.02	Affected			0.2946	0.4513		0	-1	5.3	-58.04
c.3599A>G	E1200G 2D AIThe SynGAP1 missense variant E1200G is not 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 agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-5.002	Likely Benign	0.585	Likely Pathogenic	Likely Benign										0.272	Likely Benign	-3.63	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.63	Benign	0.01	Affected			0.2541	0.4439		0	-2	3.1	-72.06
c.3670C>A	L1224M 2D AIThe SynGAP1 missense variant L1224M 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign) all indicate a tolerated change. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact. When focusing on high‑accuracy predictors, AlphaMissense‑Optimized remains benign and the SGM‑Consensus also supports a benign outcome; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this assessment does not conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500											-5.614	Likely Benign	0.098	Likely Benign	Likely Benign										0.085	Likely Benign	-0.55	Neutral	0.994	Probably Damaging	0.925	Probably Damaging	2.38	Pathogenic	0.18	Tolerated			0.0660	0.2486		4	2	-1.9	18.03
c.3671T>A	L1224Q 2D AIThe SynGAP1 missense variant L1224Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate a benign or likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports likely benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for L1224Q, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. 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	Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500											-6.254	Likely Benign	0.100	Likely Benign	Likely Benign										0.125	Likely Benign	-1.87	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	2.40	Pathogenic	0.13	Tolerated			0.1018	0.0558		-2	-2	-7.3	14.97
c.3677A>G	Q1226R 2D AIThe SynGAP1 missense change Q1226R occurs in a coiled‑coil domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-12.260	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-3.16	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.80	Pathogenic	0.00	Affected			0.1166	0.1234		1	1	-1.0	28.06
c.3677A>T	Q1226L 2D AIThe SynGAP1 missense variant Q1226L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” AlphaMissense‑Optimized is classified as “Uncertain,” and Foldetta’s protein‑folding stability analysis is unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for Q1226L. This conclusion is not contradicted by ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-11.122	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.77	Pathogenic	0.00	Affected			0.0493	0.4282		-2	-2	7.3	-14.97
c.3686A>G	Q1229R 2D AIThe SynGAP1 missense variant Q1229R is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in‑silico predictors shows a split: benign calls come from REVEL, SIFT, and AlphaMissense‑Optimized, whereas pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments further illustrate this divergence: AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote) indicates pathogenic; Foldetta data are unavailable. With five tools favoring pathogenicity versus two supporting benign, the overall prediction leans toward pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-8.998	Likely Pathogenic	0.518	Ambiguous	Likely Benign										0.282	Likely Benign	-2.53	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.80	Pathogenic	0.16	Tolerated			0.1178	0.1200		1	1	-1.0	28.06
c.3686A>T	Q1229L 2D AIThe SynGAP1 missense variant Q1229L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; the remaining tools (ESM1b and AlphaMissense‑Default) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors favor a pathogenic effect, whereas the single high‑accuracy tool suggests benign. Given the lack of ClinVar evidence, the variant is most likely pathogenic according to the collective predictions, with no contradiction to existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-7.366	In-Between	0.496	Ambiguous	Likely Benign										0.349	Likely Benign	-4.60	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.77	Pathogenic	0.09	Tolerated			0.0541	0.4253		-2	-2	7.3	-14.97
c.3707A>G	Q1236R 2D AIThe SynGAP1 missense variant Q1236R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward a benign classification, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-8.186	Likely Pathogenic	0.486	Ambiguous	Likely Benign										0.235	Likely Benign	-2.16	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	2.69	Benign	0.01	Affected			0.1110	0.1228		1	1	-1.0	28.06
c.3707A>T	Q1236L 2D AIThe SynGAP1 missense variant Q1236L is not 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, PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125											-6.682	Likely Benign	0.409	Ambiguous	Likely Benign										0.362	Likely Benign	-4.51	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.66	Benign	0.00	Affected			0.0507	0.3805		-2	-2	7.3	-14.97
c.3713A>G	Q1238R 2D AIThe SynGAP1 missense variant Q1238R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Consensus from standard predictors shows a split: benign calls come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment gives AlphaMissense‑Optimized benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the ClinVar status, which currently contains no assertion for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-10.216	Likely Pathogenic	0.477	Ambiguous	Likely Benign										0.229	Likely Benign	-2.29	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	2.40	Pathogenic	0.04	Affected			0.1165	0.2019		1	1	-1.0	28.06
c.3713A>T	Q1238L 2D AIThe SynGAP1 missense variant Q1238L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show the SGM‑Consensus as “Likely Pathogenic,” while AlphaMissense‑Optimized remains uncertain and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-14.299	Likely Pathogenic	0.876	Likely Pathogenic	Ambiguous										0.353	Likely Benign	-4.89	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.31	Pathogenic	0.01	Affected			0.0543	0.3744		-2	-2	7.3	-14.97
c.3749A>G	Q1250R 2D AIThe SynGAP1 missense variant Q1250R 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 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, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also 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 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	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-5.183	Likely Benign	0.230	Likely Benign	Likely Benign										0.148	Likely Benign	0.76	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	3.09	Benign	1.00	Tolerated			0.1330	0.0874		1	1	-1.0	28.06
c.3749A>T	Q1250L 2D AIThe SynGAP1 missense variant Q1250L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT). High‑accuracy assessments further support a benign outcome: 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 “Likely Benign.” No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar, which contains no pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-4.409	Likely Benign	0.126	Likely Benign	Likely Benign										0.092	Likely Benign	-3.49	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.65	Benign	0.02	Affected			0.0613	0.3946		-2	-2	7.3	-14.97
c.3752A>G	Q1251R 2D AIThe SynGAP1 missense variant Q1251R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-9.456	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.236	Likely Benign	-2.92	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.50	Benign	0.00	Affected			0.1257	0.1224		1	1	-1.0	28.06
c.3752A>T	Q1251L 2D AIThe SynGAP1 missense variant Q1251L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—favors pathogenicity. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-10.298	Likely Pathogenic	0.412	Ambiguous	Likely Benign										0.279	Likely Benign	-4.71	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.58	Benign	0.00	Affected			0.0626	0.4605		-2	-2	7.3	-14.97
c.3755A>G	Q1252R 2D AIThe SynGAP1 missense variant Q1252R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) support a pathogenic effect, while only one tool (REVEL) indicates benign. High‑accuracy assessments further support a deleterious impact: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, and there is no contradiction with ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-11.890	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-3.26	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1284	0.0854		1	1	-1.0	28.06
c.3755A>T	Q1252L 2D AIThe SynGAP1 missense variant Q1252L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-8.110	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous										0.295	Likely Benign	-5.62	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0593	0.3689		-2	-2	7.3	-14.97
c.3773A>G	Q1258R 2D AIThe SynGAP1 missense variant Q1258R is listed in ClinVar with an uncertain significance (ClinVar ID 3359527.0) and is not observed in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while only REVEL predicts a benign outcome. The high‑accuracy predictors give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available output for this variant. Based on the preponderance of pathogenic predictions and the SGM Consensus, the variant is most likely pathogenic, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250					Uncertain		1				-10.971	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.316	Likely Benign	-3.19	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1027	0.0991		1	1	-1.0	28.06
c.3773A>T	Q1258L 2D AIThe SynGAP1 missense variant Q1258L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) predict pathogenic, while only one tool (REVEL) predicts benign. High‑accuracy assessments further support a deleterious effect: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, indicating no conflicting evidence from population databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.302	Likely Pathogenic	0.895	Likely Pathogenic	Ambiguous										0.341	Likely Benign	-5.55	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.97	Pathogenic	0.00	Affected			0.0448	0.4137		-2	-2	7.3	-14.97
c.3868A>T	R1290W 2D AIThe SynGAP1 missense variant R1290W is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. 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 and the SGM‑Consensus (majority vote) as benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence from multiple independent predictors points to a benign impact for R1290W, 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		0.784345	Disordered	0.844138	Binding	0.567	0.795	0.625											-5.672	Likely Benign	0.294	Likely Benign	Likely Benign										0.163	Likely Benign	-5.15	Deleterious	0.994	Probably Damaging	0.920	Probably Damaging	2.58	Benign	0.00	Affected			0.0992	0.2724		2	-3	3.6	30.03
c.3958C>A	P1320T 2D AIThe SynGAP1 missense variant P1320T is reported in gnomAD (variant ID 6‑33451832‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: the majority (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a benign effect, while a minority (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT) predict pathogenicity. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, 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 preponderance of evidence from both general and high‑accuracy predictors 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		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750								6-33451832-C-A	1	6.42e-7	-5.355	Likely Benign	0.077	Likely Benign	Likely Benign										0.091	Likely Benign	-0.86	Neutral	0.994	Probably Damaging	0.981	Probably Damaging	4.21	Benign	0.00	Affected	3.77	5	0.1787	0.6392		-1	0	0.9	3.99
c.3959C>G	P1320R 2D AIThe SynGAP1 missense variant P1320R 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 interpretation: AlphaMissense‑Optimized scores the variant as 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 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		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750											-5.204	Likely Benign	0.160	Likely Benign	Likely Benign										0.142	Likely Benign	-1.39	Neutral	0.994	Probably Damaging	0.987	Probably Damaging	4.25	Benign	0.00	Affected			0.1558	0.4052		0	-2	-2.9	59.07
c.3959C>T	P1320L 2D AIThe SynGAP1 missense variant P1320L is reported in gnomAD (variant ID 6‑33451833‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign effect for P1320L, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750								6-33451833-C-T			-5.187	Likely Benign	0.094	Likely Benign	Likely Benign										0.115	Likely Benign	-1.22	Neutral	0.994	Probably Damaging	0.981	Probably Damaging	4.18	Benign	0.00	Affected	3.77	5	0.2622	0.6744		-3	-3	5.4	16.04
c.3979C>A	P1327T 2D AIThe SynGAP1 missense variant P1327T is reported in gnomAD (ID 6‑33451853‑C‑A) 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. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Taken together, 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		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875								6-33451853-C-A			-5.263	Likely Benign	0.150	Likely Benign	Likely Benign										0.144	Likely Benign	1.20	Neutral	0.994	Probably Damaging	0.908	Possibly Damaging	4.51	Benign	1.00	Tolerated	3.77	5	0.1386	0.4779		-1	0	0.9	3.99
c.3980C>G	P1327R 2D AIThe SynGAP1 missense variant P1327R is reported in gnomAD (variant ID 6‑33451854‑C‑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, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict the variant to be pathogenic. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a likely benign outcome. 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 is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875								6-33451854-C-G			-4.724	Likely Benign	0.273	Likely Benign	Likely Benign										0.137	Likely Benign	-0.95	Neutral	0.994	Probably Damaging	0.937	Probably Damaging	4.12	Benign	0.09	Tolerated	3.77	5	0.1442	0.2798		-2	0	-2.9	59.07
c.3980C>T	P1327L 2D AIThe SynGAP1 missense variant P1327L is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33451854‑C‑T). 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 high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a benign outcome. Foldetta results are not available for this variant. Overall, the majority of computational evidence supports a benign classification, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875					Uncertain		1	6-33451854-C-T	2	1.28e-6	-5.264	Likely Benign	0.242	Likely Benign	Likely Benign										0.142	Likely Benign	-1.24	Neutral	0.994	Probably Damaging	0.908	Possibly Damaging	4.12	Benign	0.10	Tolerated	3.77	5	0.2123	0.5538		-3	-3	5.4	16.04
c.3985C>A	L1329M 2D AIThe SynGAP1 missense change L1329M is recorded in gnomAD (ID 6‑33451859‑C‑A) but has no ClinVar entry. Functional prediction tools split into two consensus groups: benign‑predicted by REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic‑predicted by polyPhen‑2 (HumDiv and 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 further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus likewise indicates benign. Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points 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		0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451859-C-A			-5.493	Likely Benign	0.780	Likely Pathogenic	Likely Benign										0.087	Likely Benign	-1.16	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.10	Benign	0.00	Affected	3.77	5	0.0914	0.4273		2	4	-1.9	18.03
c.3986T>A	L1329Q 2D AIThe SynGAP1 missense variant L1329Q is reported in gnomAD (ID 6‑33451860‑T‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions are made by 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 (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a deleterious effect, indicating that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451860-T-A			-4.106	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.157	Likely Benign	-3.31	Deleterious	0.994	Probably Damaging	0.993	Probably Damaging	3.05	Benign	0.00	Affected	3.77	5	0.1382	0.1505		-2	-2	-7.3	14.97
c.3986T>C	L1329P 2D AIThe SynGAP1 missense variant L1329P is listed in gnomAD (ID 6‑33451860‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie and is therefore inconclusive. No Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors (five pathogenic vs three benign) lean toward a pathogenic effect. Because ClinVar contains no classification, there is no conflict with existing clinical annotation. Thus, based on current in silico evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451860-T-C			-2.903	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-3.74	Deleterious	0.994	Probably Damaging	0.993	Probably Damaging	3.04	Benign	0.00	Affected	3.77	5	0.3396	0.1794		-3	-3	-5.4	-16.04