Data | SynGAP Server

c.dna	Variant	SGM Consensus	Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	ClinVar			gnomAD			ESM1b		AlphaMissense			REVEL		PSMutPred			FoldX			Rosetta		Foldetta		PremPS		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation									DOI
c.dna	Variant	SGM Consensus	Domain	Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Score	Prediction	IP RF	SP RF	Prediction	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	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	DOI
c.3081C>A	N1027K 2D AIThe SynGAP1 missense variant N1027K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv 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 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		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500							-3.177	Likely Benign	0.841	Likely Pathogenic	Ambiguous	0.063	Likely Benign	0.1808	0.6079											-0.64	Neutral	0.481	Possibly Damaging	0.220	Benign	2.81	Benign	0.65	Tolerated			1	0	-0.4	14.07													MD Alert	Verdict	Description
c.3081C>G	N1027K 2D AIThe SynGAP1 missense variant N1027K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is 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		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500							-3.177	Likely Benign	0.841	Likely Pathogenic	Ambiguous	0.063	Likely Benign	0.1808	0.6079											-0.64	Neutral	0.481	Possibly Damaging	0.220	Benign	2.81	Benign	0.65	Tolerated			1	0	-0.4	14.07
c.823C>A	P275T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P275T is reported in gnomAD (ID 6‑33437728‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The high‑accuracy AlphaMissense‑Optimized score is benign, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain and therefore not considered evidence. No other tools provide conclusive results. Overall, the majority of predictions, including the SGM‑Consensus, indicate a pathogenic effect, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.059222	Structured	0.353469	Uncertain	0.811	0.208	0.250				6-33437728-C-A	3	1.86e-6	-8.708	Likely Pathogenic	0.309	Likely Benign	Likely Benign	0.425	Likely Benign	0.1808	0.4000		2.44	Destabilizing	0.3	1.15	Ambiguous	1.80	Ambiguous	0.69	Ambiguous	-5.38	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.75	Pathogenic	0.01	Affected	3.38	19	-1	0	0.9	3.99
c.2651G>T	R884L 2D AIThe SynGAP1 missense variant R884L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.641526	Binding	0.305	0.898	0.250							-3.482	Likely Benign	0.280	Likely Benign	Likely Benign	0.095	Likely Benign	0.1809	0.4177											-1.08	Neutral	0.300	Benign	0.191	Benign	2.63	Benign	0.24	Tolerated			-3	-2	8.3	-43.03
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	0.1809	0.4075											-1.89	Neutral	0.992	Probably Damaging	0.615	Possibly Damaging	3.90	Benign	0.00	Affected			0	-1	5.8	3.02
c.44C>T	A15V 2D AIThe SynGAP1 missense variant A15V is listed in ClinVar (ID 1801174.0) with an “Uncertain” status and is present in gnomAD (6‑33420308‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. 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 majority of evidence points to a benign effect, and this does not contradict the ClinVar designation, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.466055	Uncertain	0.330	0.912	0.375	Uncertain		1	6-33420308-C-T	1	6.49e-7	-3.560	Likely Benign	0.161	Likely Benign	Likely Benign	0.105	Likely Benign	0.1809	0.7669											0.20	Neutral	0.602	Possibly Damaging	0.015	Benign	4.19	Benign	0.00	Affected	4.32	1	0	0	2.4	28.05
c.710C>G	A237G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A237G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Given the balance of evidence, 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.	Likely Benign	PH	0.200174	Structured	0.334699	Uncertain	0.719	0.352	0.000							-6.647	Likely Benign	0.316	Likely Benign	Likely Benign	0.538	Likely Pathogenic	0.1809	0.2910		1.00	Ambiguous	0.0	2.01	Destabilizing	1.51	Ambiguous	1.14	Destabilizing	-2.91	Deleterious	0.900	Possibly Damaging	0.430	Benign	5.81	Benign	0.05	Affected			1	0	-2.2	-14.03
c.8G>C	R3T 2D AIThe SynGAP1 missense variant R3T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.550331	Binding	0.358	0.920	0.875							-3.693	Likely Benign	0.285	Likely Benign	Likely Benign	0.053	Likely Benign	0.1809	0.5145											-0.55	Neutral	0.208	Benign	0.018	Benign	4.01	Benign	0.00	Affected			-1	-1	3.8	-55.08
c.1486G>A	E496K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E496K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FoldX, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. Uncertain predictions come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Overall, the evidence strongly favors a pathogenic classification for E496K, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.383296	Uncertain	0.945	0.179	0.000							-15.795	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.743	Likely Pathogenic	0.1810	0.3528		0.38	Likely Benign	0.1	1.77	Ambiguous	1.08	Ambiguous	0.76	Ambiguous	-3.58	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.40	Pathogenic	0.04	Affected			0	1	-0.4	-0.94
c.1834C>A	Q612K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q612K is not reported in ClinVar (ClinVar status: not listed) and has no entry in gnomAD (gnomAD ID: none). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and SIFT, whereas pathogenic predictions come from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; premPS and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools predict pathogenicity, and the high‑accuracy consensus also leans pathogenic, while the folding‑stability method suggests benign. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no classification. 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							-12.393	Likely Pathogenic	0.849	Likely Pathogenic	Ambiguous	0.619	Likely Pathogenic	0.1810	0.3641		0.15	Likely Benign	0.1	0.48	Likely Benign	0.32	Likely Benign	0.81	Ambiguous	-3.88	Deleterious	0.931	Possibly Damaging	0.931	Probably Damaging	-1.22	Pathogenic	0.19	Tolerated			1	1	-0.4	0.04
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	0.1810	0.2401											-1.76	Neutral	0.984	Probably Damaging	0.601	Possibly Damaging	4.19	Benign	0.08	Tolerated			0	-2	-2.9	59.07
c.1979T>C	M660T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660T is catalogued in gnomAD (ID 6‑33441238‑T‑C) but has no ClinVar entry, so its clinical status is currently unreported. In silico prediction tools largely agree that the substitution is deleterious: pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign effect. High‑accuracy assessments reinforce the pathogenic view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or folding result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000				6-33441238-T-C	1	6.20e-7	-9.791	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.561	Likely Pathogenic	0.1811	0.1630		3.62	Destabilizing	0.1	2.05	Destabilizing	2.84	Destabilizing	1.91	Destabilizing	-5.99	Deleterious	0.967	Probably Damaging	0.633	Possibly Damaging	3.36	Benign	0.02	Affected	3.38	28	-1	-1	-2.6	-30.09
c.1982A>C	Q661P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q661P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from premPS and FATHMM, whereas the remaining 12 tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score) all classify the change as pathogenic or likely pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a pathogenic effect. No prediction is inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000							-17.549	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.531	Likely Pathogenic	0.1811	0.3850		4.11	Destabilizing	0.1	5.97	Destabilizing	5.04	Destabilizing	0.45	Likely Benign	-4.58	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.41	Benign	0.01	Affected			0	-1	1.9	-31.01
c.2060G>C	R687P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R687P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas the remaining eleven tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. With the overwhelming majority of evidence pointing to a damaging effect and no conflicting ClinVar annotation, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000							-15.697	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.553	Likely Pathogenic	0.1811	0.3159		2.31	Destabilizing	0.3	6.63	Destabilizing	4.47	Destabilizing	0.89	Ambiguous	-6.12	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.87	Benign	0.01	Affected			0	-2	2.9	-59.07
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	0.1812	0.4822											-1.68	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.65	Benign	0.00	Affected	4.32	1	1	1	-2.7	27.03
c.3037T>A	S1013T 2D AIThe SynGAP1 missense variant S1013T is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is 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		0.823549	Disordered	0.899570	Binding	0.308	0.846	0.625							-4.245	Likely Benign	0.086	Likely Benign	Likely Benign	0.051	Likely Benign	0.1812	0.6039											-0.96	Neutral	0.069	Benign	0.072	Benign	2.70	Benign	0.26	Tolerated			1	1	0.1	14.03
c.1780T>G	F594V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594V lies within the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that assess pathogenicity unanimously favor a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity; only Rosetta is uncertain. No tool 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) is pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000							-12.648	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.931	Likely Pathogenic	0.1813	0.1575		2.91	Destabilizing	0.2	1.90	Ambiguous	2.41	Destabilizing	1.80	Destabilizing	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.91	Pathogenic	0.01	Affected			-1	-1	1.4	-48.04
c.1953G>C	E651D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E651D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen2_HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign prediction. No prediction tool or stability analysis is inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000							-3.220	Likely Benign	0.231	Likely Benign	Likely Benign	0.153	Likely Benign	0.1813	0.3762		0.16	Likely Benign	0.1	0.33	Likely Benign	0.25	Likely Benign	-0.29	Likely Benign	-0.13	Neutral	0.906	Possibly Damaging	0.429	Benign	3.48	Benign	0.53	Tolerated			3	2	0.0	-14.03
c.1953G>T	E651D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E651D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only polyPhen2_HumDiv predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign prediction. No prediction tool or stability analysis is inconclusive or missing. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000							-3.220	Likely Benign	0.231	Likely Benign	Likely Benign	0.153	Likely Benign	0.1813	0.3762		0.16	Likely Benign	0.1	0.33	Likely Benign	0.25	Likely Benign	-0.29	Likely Benign	-0.13	Neutral	0.906	Possibly Damaging	0.429	Benign	3.48	Benign	0.53	Tolerated			3	2	0.0	-14.03
c.3385C>G	L1129V 2D AIThe SynGAP1 missense variant L1129V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that 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		0.903857	Disordered	0.876543	Binding	0.339	0.909	0.875							-3.595	Likely Benign	0.093	Likely Benign	Likely Benign	0.262	Likely Benign	0.1814	0.3804											-0.87	Neutral	0.393	Benign	0.187	Benign	5.46	Benign	0.00	Affected			2	1	0.4	-14.03
c.3839T>C	M1280T 2D AIThe SynGAP1 missense variant M1280T is catalogued in gnomAD (6‑33447887‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. In contrast, SIFT and FATHMM predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875				6-33447887-T-C	3	1.93e-6	-2.305	Likely Benign	0.112	Likely Benign	Likely Benign	0.158	Likely Benign	0.1814	0.2031											-2.26	Neutral	0.369	Benign	0.120	Benign	2.34	Pathogenic	0.00	Affected	3.77	5	-1	-1	-2.6	-30.09
c.3973C>A	P1325T 2D AIThe SynGAP1 missense variant P1325T is reported in gnomAD (ID 6‑33451847‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. 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 preponderance of evidence points to a benign effect for P1325T, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.893621	Binding	0.439	0.791	0.875				6-33451847-C-A			-5.880	Likely Benign	0.083	Likely Benign	Likely Benign	0.135	Likely Benign	0.1814	0.5150											-0.14	Neutral	0.000	Benign	0.001	Benign	4.07	Benign	0.00	Affected	4.32	1	-1	0	0.9	3.99
c.1273A>C	T425P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as deleterious, while only FATHMM predicts a benign outcome; premPS is uncertain. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. Taken together, the overwhelming majority of evidence supports a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000							-12.318	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.512	Likely Pathogenic	0.1815	0.3469		2.81	Destabilizing	0.3	6.49	Destabilizing	4.65	Destabilizing	0.77	Ambiguous	-5.16	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.03	Affected			0	-1	-0.9	-3.99
c.2348T>G	M783R 2D AIThe SynGAP1 missense variant M783R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward a pathogenic impact. 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.			0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625							-3.849	Likely Benign	0.655	Likely Pathogenic	Likely Benign	0.208	Likely Benign	0.1815	0.0893											-2.69	Deleterious	0.925	Possibly Damaging	0.529	Possibly Damaging	2.66	Benign	0.01	Affected			0	-1	-6.4	24.99
c.2990C>A	A997D 2D AIThe SynGAP1 missense variant A997D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of any ClinVar pathogenic annotation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.948624	Binding	0.273	0.901	0.500							-5.251	Likely Benign	0.319	Likely Benign	Likely Benign	0.131	Likely Benign	0.1815	0.2143											-1.09	Neutral	0.411	Benign	0.120	Benign	4.15	Benign	0.00	Affected			0	-2	-5.3	44.01
c.878G>T	R293L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R293L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are made by REVEL and premPS, while the remaining evaluated tools (SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict pathogenicity. Uncertain results from FoldX, Rosetta, and Foldetta are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta provides no definitive stability change. Consequently, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.338192	Uncertain	0.924	0.269	0.125							-15.502	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.493	Likely Benign	0.1815	0.4987		1.56	Ambiguous	0.2	0.93	Ambiguous	1.25	Ambiguous	0.08	Likely Benign	-6.43	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.46	Pathogenic	0.01	Affected			-3	-2	8.3	-43.03
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	0.1816	0.4797											-1.47	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.60	Pathogenic	0.21	Tolerated			1	1	-0.4	0.04
c.1430T>A	M477K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS and FATHMM. Predictions that are uncertain or inconclusive are FoldX, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is unavailable due to mixed or uncertain inputs. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict the current ClinVar status, which contains no report of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000							-7.519	In-Between	0.553	Ambiguous	Likely Benign	0.371	Likely Benign	0.1817	0.0847		0.54	Ambiguous	0.1	0.37	Likely Benign	0.46	Likely Benign	1.12	Destabilizing	-1.32	Neutral	0.254	Benign	0.122	Benign	-1.15	Pathogenic	0.14	Tolerated			0	-1	-5.8	-3.02
c.1666A>G	N556D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556D is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With two of the three high‑accuracy tools indicating benign and an equal split among the broader set of predictors, the variant is most likely benign. 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	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000							-6.787	Likely Benign	0.704	Likely Pathogenic	Likely Benign	0.546	Likely Pathogenic	0.1817	0.1625		0.41	Likely Benign	0.0	0.39	Likely Benign	0.40	Likely Benign	0.33	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.33	Pathogenic	0.08	Tolerated			2	1	0.0	0.98
c.2444G>T	R815L 2D AISynGAP1 missense variant R815L is listed in ClinVar (ID 2505666.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools indicates a pathogenic effect, which contrasts with the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250	Uncertain		1				-8.546	Likely Pathogenic	0.865	Likely Pathogenic	Ambiguous	0.175	Likely Benign	0.1817	0.5132											-3.06	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.63	Benign	0.03	Affected	4.32	4	-2	-3	8.3	-43.03
c.2932C>A	P978T 2D AIThe SynGAP1 missense variant P978T is not 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							-4.949	Likely Benign	0.217	Likely Benign	Likely Benign	0.125	Likely Benign	0.1817	0.7089											-1.23	Neutral	0.818	Possibly Damaging	0.453	Possibly Damaging	4.21	Benign	0.04	Affected			0	-1	0.9	3.99
c.3191A>T	Q1064L 2D AIThe SynGAP1 missense variant Q1064L is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978316	Disordered	0.953106	Binding	0.378	0.914	0.875							-3.492	Likely Benign	0.099	Likely Benign	Likely Benign	0.133	Likely Benign	0.1817	0.5485											-1.16	Neutral	0.224	Benign	0.091	Benign	4.20	Benign	0.13	Tolerated			-2	-2	7.3	-14.97
c.3067T>C	S1023P 2D AIThe SynGAP1 missense variant S1023P is reported in gnomAD (ID 6‑33443619‑T‑C) but has no ClinVar entry (ClinVar status: not reported). Functional prediction tools are split: benign calls come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, SGM Consensus remains inconclusive, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the majority of standard predictors lean toward pathogenicity, whereas the few high‑accuracy tools do not support a pathogenic verdict. Thus, the variant is most likely pathogenic based on the aggregate predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.831250	Disordered	0.990262	Binding	0.322	0.750	0.500				6-33443619-T-C	2	1.24e-6	-5.634	Likely Benign	0.679	Likely Pathogenic	Likely Benign	0.146	Likely Benign	0.1818	0.4616											-2.11	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.43	Pathogenic	0.02	Affected	3.77	5	-1	1	-0.8	10.04
c.3427A>C	T1143P 2D AIThe SynGAP1 missense variant T1143P 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. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic effect. 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 is present). 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							-2.307	Likely Benign	0.155	Likely Benign	Likely Benign	0.183	Likely Benign	0.1818	0.4108											0.80	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.69	Benign	0.24	Tolerated			0	-1	-0.9	-3.99
c.1310C>A	P437H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the balance of evidence favors a pathogenic classification for P437H, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000							-13.496	Likely Pathogenic	0.826	Likely Pathogenic	Ambiguous	0.343	Likely Benign	0.1819	0.4328		1.19	Ambiguous	0.0	-3.28	Stabilizing	-1.05	Ambiguous	0.31	Likely Benign	-7.75	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.44	Benign	0.01	Affected			0	-2	-1.6	40.02
c.2528T>G	M843R 2D AIThe SynGAP1 missense variant M843R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that M843R is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375							-12.044	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.430	Likely Benign	0.1819	0.0922											-3.78	Deleterious	0.968	Probably Damaging	0.978	Probably Damaging	2.59	Benign	0.00	Affected			0	-1	-6.4	24.99
c.1477G>T	A493S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A493S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Predictions that are uncertain or inconclusive (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as unavailable. Based on the consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000							-6.271	Likely Benign	0.298	Likely Benign	Likely Benign	0.507	Likely Pathogenic	0.1821	0.2763		0.66	Ambiguous	0.1	1.10	Ambiguous	0.88	Ambiguous	0.53	Ambiguous	-2.12	Neutral	0.983	Probably Damaging	0.993	Probably Damaging	-1.27	Pathogenic	0.44	Tolerated			1	1	-2.6	16.00
c.2798A>C	H933P 2D AIThe SynGAP1 missense variant H933P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, six tools predict pathogenicity versus three predicting benign, and the high‑accuracy benign prediction is outweighed by the majority of pathogenic calls. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625							-3.890	Likely Benign	0.332	Likely Benign	Likely Benign	0.508	Likely Pathogenic	0.1821	0.4400											-5.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.36	Pathogenic	0.02	Affected			0	-2	1.6	-40.02
c.283C>A	H95N 2D AIThe SynGAP1 missense variant H95N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the computational evidence overwhelmingly supports a benign classification for H95N, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.590542	Binding	0.335	0.875	0.625							-3.454	Likely Benign	0.069	Likely Benign	Likely Benign	0.089	Likely Benign	0.1821	0.2491											-1.12	Neutral	0.219	Benign	0.009	Benign	4.20	Benign	0.00	Affected			2	1	-0.3	-23.04
c.3844G>A	E1282K 2D AIThe SynGAP1 missense variant E1282K is catalogued in gnomAD (ID 6‑33447892‑G‑A) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool examined—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classifies the substitution as benign. No pathogenic predictions are reported. Grouping by consensus, all listed tools fall into the benign category, with no tools indicating pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign effect for E1282K, and this conclusion does not contradict any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.817364	Binding	0.465	0.725	0.875				6-33447892-G-A			-3.805	Likely Benign	0.226	Likely Benign	Likely Benign	0.173	Likely Benign	0.1821	0.5809											-1.17	Neutral	0.126	Benign	0.026	Benign	2.73	Benign	0.16	Tolerated	3.77	5	1	0	-0.4	-0.94
c.1703T>G	V568G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568G is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID 6‑33440755‑T‑G). Prediction tools that agree on a pathogenic effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000				6-33440755-T-G			-15.135	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.933	Likely Pathogenic	0.1822	0.1877		3.39	Destabilizing	0.1	4.45	Destabilizing	3.92	Destabilizing	2.34	Destabilizing	-6.81	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.46	Pathogenic	0.00	Affected	3.37	35	-3	-1	-4.6	-42.08
c.1078G>C	E360Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and premPS, while a majority of tools predict a pathogenic outcome: SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360Q, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250							-11.012	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.343	Likely Benign	0.1824	0.8282		0.55	Ambiguous	0.1	1.38	Ambiguous	0.97	Ambiguous	-0.02	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.61	Pathogenic	0.03	Affected			2	2	0.0	-0.98
c.2351C>A	A784D 2D AIThe SynGAP1 missense variant A784D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625							-3.784	Likely Benign	0.766	Likely Pathogenic	Likely Benign	0.206	Likely Benign	0.1824	0.2193											-1.21	Neutral	0.411	Benign	0.237	Benign	2.68	Benign	0.16	Tolerated			0	-2	-5.3	44.01
c.3161G>A	G1054D 2D AISynGAP1 missense variant G1054D is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates the variant is most likely benign, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.983019	Disordered	0.878015	Binding	0.389	0.936	0.875	Uncertain		1				-10.385	Likely Pathogenic	0.351	Ambiguous	Likely Benign	0.279	Likely Benign	0.1824	0.2035											-0.26	Neutral	0.818	Possibly Damaging	0.266	Benign	4.07	Benign	0.37	Tolerated	3.77	5	1	-1	-3.1	58.04
c.589G>A	E197K 2D AIThe SynGAP1 missense variant E197K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, whereas pathogenic calls arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized. Grouping by consensus, the majority of high‑confidence predictors (AlphaMissense‑Optimized, SGM‑Consensus, PROVEAN, SIFT, ESM1b) indicate pathogenicity, while a minority (REVEL, polyPhen‑2, FATHMM) suggest benign impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, is classified as Likely Pathogenic. AlphaMissense‑Optimized also predicts Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E197K, and this assessment does not conflict with ClinVar, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.349426	Structured	0.431896	Uncertain	0.452	0.492	0.125							-11.045	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.198	Likely Benign	0.1824	0.5890											-2.50	Deleterious	0.118	Benign	0.037	Benign	4.09	Benign	0.02	Affected			0	1	-0.4	-0.94
c.1681T>A	F561I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561I is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (variant ID 6‑33440733‑T‑A). Prediction tools that agree on a benign effect include only SIFT. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000				6-33440733-T-A	1	6.32e-7	-11.708	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.710	Likely Pathogenic	0.1825	0.1925		3.82	Destabilizing	0.1	2.13	Destabilizing	2.98	Destabilizing	1.46	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.06	Pathogenic	0.09	Tolerated	3.37	35	0	1	1.7	-34.02
c.2119G>T	A707S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A707S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 HumDiv and HumVar classify the variant as pathogenic. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000							-4.432	Likely Benign	0.113	Likely Benign	Likely Benign	0.150	Likely Benign	0.1825	0.2924		0.70	Ambiguous	0.1	0.63	Ambiguous	0.67	Ambiguous	0.28	Likely Benign	-1.07	Neutral	0.848	Possibly Damaging	0.945	Probably Damaging	3.43	Benign	0.08	Tolerated			1	1	-2.6	16.00
c.3832C>A	P1278T 2D AIThe SynGAP1 missense variant P1278T is catalogued in gnomAD (ID 6‑33447880‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this assessment does not contradict any ClinVar classification. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.806955	Binding	0.532	0.722	0.750				6-33447880-C-A			-5.505	Likely Benign	0.095	Likely Benign	Likely Benign	0.064	Likely Benign	0.1825	0.4053											-0.60	Neutral	0.059	Benign	0.026	Benign	2.73	Benign	0.11	Tolerated	3.77	5	-1	0	0.9	3.99
c.761A>C	K254T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K254T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, PROVEAN, both polyPhen‑2 HumDiv and HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Benign predictions are limited to SIFT and FATHMM. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points to a pathogenic effect for K254T, and this conclusion does not conflict with ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375							-13.793	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.883	Likely Pathogenic	0.1825	0.2562		0.51	Ambiguous	0.0	1.92	Ambiguous	1.22	Ambiguous	0.62	Ambiguous	-5.14	Deleterious	0.970	Probably Damaging	0.749	Possibly Damaging	5.88	Benign	0.06	Tolerated			0	-1	3.2	-27.07
c.160A>G	N54D 2D AIThe SynGAP1 missense variant N54D is not 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 labeled “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 (a 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 conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000							-6.980	Likely Benign	0.325	Likely Benign	Likely Benign	0.074	Likely Benign	0.1826	0.4496											-0.75	Neutral	0.458	Possibly Damaging	0.678	Possibly Damaging	4.22	Benign	0.00	Affected			2	1	0.0	0.98
c.2167A>C	T723P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T723P is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that predict pathogenicity are SGM Consensus, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. premPS is uncertain and does not influence the overall assessment. Overall, the majority of tools and the high‑accuracy methods support a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458243	Uncertain	0.945	0.447	0.375							-9.231	Likely Pathogenic	0.741	Likely Pathogenic	Likely Benign	0.085	Likely Benign	0.1826	0.4406		3.98	Destabilizing	0.1	6.10	Destabilizing	5.04	Destabilizing	0.54	Ambiguous	-2.51	Deleterious	0.995	Probably Damaging	0.929	Probably Damaging	3.49	Benign	0.04	Affected			0	-1	-0.9	-3.99
c.2270G>A	G757D 2D AIThe SynGAP1 missense variant G757D is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only polyPhen‑2 HumDiv flags it as pathogenic, while AlphaMissense‑Default remains uncertain. 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. Taken together, the preponderance of evidence supports a benign interpretation, and this assessment does not contradict any ClinVar annotation (none is present). Therefore, the variant is most likely benign, with no conflict with ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.830995	Binding	0.310	0.869	0.375							-4.613	Likely Benign	0.387	Ambiguous	Likely Benign	0.150	Likely Benign	0.1826	0.1611											-0.90	Neutral	0.454	Possibly Damaging	0.192	Benign	2.71	Benign	0.11	Tolerated			1	-1	-3.1	58.04
c.3649G>A	E1217K 2D AIThe SynGAP1 missense variant E1217K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250							-12.869	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	0.306	Likely Benign	0.1826	0.5272											-3.09	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.40	Pathogenic	0.00	Affected			0	1	-0.4	-0.94
c.3846G>C	E1282D 2D AIThe SynGAP1 missense variant E1282D is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6-33447894-G-C). All available in silico predictors classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic prediction. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its status is unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.817364	Binding	0.465	0.725	0.875	Uncertain		1	6-33447894-G-C	1	6.44e-7	-3.879	Likely Benign	0.074	Likely Benign	Likely Benign	0.104	Likely Benign	0.1826	0.3464											-1.26	Neutral	0.112	Benign	0.036	Benign	2.70	Benign	0.39	Tolerated	3.77	5	3	2	0.0	-14.03
c.3846G>T	E1282D 2D AIThe SynGAP1 missense variant E1282D is reported in gnomAD (ID 6‑33447894‑G‑T) but has no ClinVar entry. All in‑silico predictors reviewed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as benign. No tool predicts pathogenicity, so the benign group includes every listed predictor, while the pathogenic group is empty. High‑accuracy assessments further support a benign effect: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, 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		0.754692	Disordered	0.817364	Binding	0.465	0.725	0.875				6-33447894-G-T			-3.879	Likely Benign	0.074	Likely Benign	Likely Benign	0.104	Likely Benign	0.1826	0.3464											-1.26	Neutral	0.112	Benign	0.036	Benign	2.70	Benign	0.39	Tolerated	3.77	5	3	2	0.0	-14.03
c.3316C>A	Q1106K 2D AIThe SynGAP1 missense variant Q1106K is catalogued in gnomAD (ID 6‑33443868‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions arise from 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 the votes are split (two benign, one pathogenic, one uncertain). Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence favors a benign effect, 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.			0.885302	Disordered	0.952043	Binding	0.382	0.870	0.875				6-33443868-C-A			-3.368	Likely Benign	0.527	Ambiguous	Likely Benign	0.115	Likely Benign	0.1827	0.4800											-2.49	Neutral	0.963	Probably Damaging	0.959	Probably Damaging	1.82	Pathogenic	0.16	Tolerated	3.77	5	1	1	-0.4	0.04
c.986G>T	R329L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R329L has no ClinVar entry and is not reported in gnomAD. Consensus from standard prediction tools shows a split: benign calls come from REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar, while pathogenic calls arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked uncertain (Rosetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the majority of tools lean toward pathogenicity, but the folding‑stability evidence suggests a benign effect. Given the lack of ClinVar annotation, there is no contradiction. The variant is most likely pathogenic based on the preponderance of pathogenic predictions, though the benign folding‑stability result introduces uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250							-10.186	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.219	Likely Benign	0.1827	0.4121		-0.09	Likely Benign	0.4	0.53	Ambiguous	0.22	Likely Benign	0.54	Ambiguous	-4.81	Deleterious	0.653	Possibly Damaging	0.361	Benign	4.02	Benign	0.01	Affected			-3	-2	8.3	-43.03
c.1438G>A	E480K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E480K is catalogued in gnomAD (ID 6‑33438470‑G‑A) but has no entry in ClinVar. Functional prediction tools cluster into two groups: benign predictions come from FoldX and SIFT, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported by Rosetta, Foldetta, and premPS. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence indicates that E480K 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	0.216401	Structured	0.426867	Uncertain	0.798	0.250	0.000				6-33438470-G-A	1	6.20e-7	-14.059	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.768	Likely Pathogenic	0.1828	0.6813		0.40	Likely Benign	0.1	1.08	Ambiguous	0.74	Ambiguous	0.83	Ambiguous	-3.45	Deleterious	0.996	Probably Damaging	0.987	Probably Damaging	-1.26	Pathogenic	0.11	Tolerated	3.37	34	1	0	-0.4	-0.94
c.2801T>A	M934K 2D AIThe SynGAP1 missense variant M934K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence from the majority of tools points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625							-2.457	Likely Benign	0.816	Likely Pathogenic	Ambiguous	0.333	Likely Benign	0.1828	0.1262											-3.66	Deleterious	0.929	Possibly Damaging	0.521	Possibly Damaging	2.38	Pathogenic	0.13	Tolerated			0	-1	-5.8	-3.02
c.370G>A	A124T 2D AIThe SynGAP1 missense variant A124T is reported in gnomAD (6-33432235‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact. 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		0.509769	Disordered	0.699139	Binding	0.340	0.883	0.750				6-33432235-G-A	1	6.20e-7	-3.551	Likely Benign	0.101	Likely Benign	Likely Benign	0.046	Likely Benign	0.1828	0.7680											-0.26	Neutral	0.734	Possibly Damaging	0.187	Benign	4.17	Benign	0.78	Tolerated	3.61	5	0	1	-2.5	30.03
c.3677A>C	Q1226P 2D AIThe SynGAP1 missense variant Q1226P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250							-13.176	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.418	Likely Benign	0.1829	0.4187											-4.72	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.75	Pathogenic	0.00	Affected			0	-1	1.9	-31.01
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	0.497	Likely Benign	0.1830	0.2349		1.92	Ambiguous	0.5	0.29	Likely Benign	1.11	Ambiguous	0.89	Ambiguous	-6.86	Deleterious	0.993	Probably Damaging	0.968	Probably Damaging	3.50	Benign	0.01	Affected			-1	-1	1.4	-48.04
c.2096T>G	V699G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V699G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FATHMM and AlphaMissense‑Optimized, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b) uniformly predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict; and Foldetta also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.069024	Structured	0.432975	Uncertain	0.935	0.315	0.000							-11.912	Likely Pathogenic	0.481	Ambiguous	Likely Benign	0.514	Likely Pathogenic	0.1830	0.2240		2.22	Destabilizing	0.0	3.25	Destabilizing	2.74	Destabilizing	1.77	Destabilizing	-5.11	Deleterious	0.972	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.01	Affected			-1	-3	-4.6	-42.08
c.2581T>C	S861P 2D AIThe SynGAP1 missense variant S861P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for S861P, 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		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250							-4.256	Likely Benign	0.107	Likely Benign	Likely Benign	0.116	Likely Benign	0.1830	0.6011											-1.65	Neutral	0.960	Probably Damaging	0.761	Possibly Damaging	3.93	Benign	0.13	Tolerated			1	-1	-0.8	10.04
c.294T>A	H98Q 2D AIThe SynGAP1 missense variant H98Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: 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 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		0.733139	Disordered	0.631713	Binding	0.348	0.872	0.625							-2.749	Likely Benign	0.104	Likely Benign	Likely Benign	0.088	Likely Benign	0.1831	0.4347											-0.47	Neutral	0.002	Benign	0.000	Benign	4.26	Benign	0.00	Affected			3	0	-0.3	-9.01
c.294T>G	H98Q 2D AIThe SynGAP1 missense variant H98Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: 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 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		0.733139	Disordered	0.631713	Binding	0.348	0.872	0.625							-2.749	Likely Benign	0.104	Likely Benign	Likely Benign	0.088	Likely Benign	0.1831	0.4347											-0.47	Neutral	0.002	Benign	0.000	Benign	4.26	Benign	0.00	Affected			3	0	-0.3	-9.01
c.3012C>A	H1004Q 2D AIThe SynGAP1 missense variant H1004Q is not 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 the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750							-3.872	Likely Benign	0.853	Likely Pathogenic	Ambiguous	0.126	Likely Benign	0.1831	0.3832											-1.55	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.78	Benign	0.71	Tolerated	3.77	5	0	3	-0.3	-9.01
c.3012C>G	H1004Q 2D AIThe SynGAP1 missense variant H1004Q is catalogued in gnomAD (ID 6‑33443564‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while PolyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default 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 show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “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 (six benign predictions versus three pathogenic) indicates that H1004Q 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.	Likely Benign		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750				6-33443564-C-G	3	1.86e-6	-3.872	Likely Benign	0.853	Likely Pathogenic	Ambiguous	0.126	Likely Benign	0.1831	0.3832											-1.55	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.78	Benign	0.71	Tolerated	3.77	5	0	3	-0.3	-9.01
c.2734A>C	T912P 2D AIThe SynGAP1 missense variant T912P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. 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		0.724957	Disordered	0.740671	Binding	0.285	0.909	0.250							-2.955	Likely Benign	0.111	Likely Benign	Likely Benign	0.087	Likely Benign	0.1832	0.4608											-0.78	Neutral	0.217	Benign	0.121	Benign	4.00	Benign	0.00	Affected			0	-1	-0.9	-3.99
c.2804C>A	A935D 2D AIThe SynGAP1 missense variant A935D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A935D, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625							-4.089	Likely Benign	0.817	Likely Pathogenic	Ambiguous	0.247	Likely Benign	0.1832	0.1860											-2.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.31	Pathogenic	0.00	Affected			0	-2	-5.3	44.01
c.977A>G	H326R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H326R missense variant is not listed in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include SIFT and Foldetta, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as likely pathogenic; Foldetta, a protein‑folding stability approach that integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Because the majority of evidence points to a deleterious change, the variant is most likely pathogenic, and this assessment is not contradicted by the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000							-12.369	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.601	Likely Pathogenic	0.1832	0.2413		-0.65	Ambiguous	0.1	1.40	Ambiguous	0.38	Likely Benign	0.83	Ambiguous	-6.89	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.97	Pathogenic	0.10	Tolerated			2	0	-1.3	19.05
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	0.1833	0.6209											-0.33	Neutral	0.992	Probably Damaging	0.814	Possibly Damaging	2.50	Benign	0.78	Tolerated			1	1	0.1	14.03
c.2831G>A	G944D 2D AIThe SynGAP1 missense variant G944D is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools largely support a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the majority‑vote SGM‑Consensus also indicates a likely benign outcome. Only SIFT predicts a pathogenic effect, and ESM1b remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign classification. Foldetta stability analysis is not available for this residue. Overall, the preponderance 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		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750							-7.684	In-Between	0.296	Likely Benign	Likely Benign	0.421	Likely Benign	0.1833	0.2826											-1.42	Neutral	0.224	Benign	0.131	Benign	3.70	Benign	0.00	Affected			1	-1	-3.1	58.04
c.2867C>G	S956C 2D AIThe SynGAP1 missense variant S956C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate 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.			0.984871	Disordered	0.957345	Binding	0.364	0.917	0.750							-9.292	Likely Pathogenic	0.108	Likely Benign	Likely Benign	0.107	Likely Benign	0.1833	0.5470											-0.34	Neutral	0.938	Possibly Damaging	0.665	Possibly Damaging	1.94	Pathogenic	0.03	Affected			0	-1	3.3	16.06
c.124C>A	P42T 2D AIThe SynGAP1 missense variant P42T is not 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 P42T, and 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		0.308712	Structured	0.431487	Uncertain	0.420	0.771	0.375							-3.626	Likely Benign	0.101	Likely Benign	Likely Benign	0.109	Likely Benign	0.1834	0.4896											-0.97	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.29	Benign	0.00	Affected			0	-1	0.9	3.99
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	0.1834	0.5066											-0.69	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	4.23	Benign	0.00	Affected	4.32	1	-2	0	-1.6	40.02
c.1094T>G	V365G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250							-13.020	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.576	Likely Pathogenic	0.1835	0.2717		4.18	Destabilizing	0.2	4.83	Destabilizing	4.51	Destabilizing	2.18	Destabilizing	-5.88	Deleterious	0.688	Possibly Damaging	0.989	Probably Damaging	1.66	Pathogenic	0.00	Affected			-1	-3	-4.6	-42.08
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	0.262	Likely Benign	0.1835	0.2391		1.41	Ambiguous	0.2	0.48	Likely Benign	0.95	Ambiguous	0.96	Ambiguous	-3.18	Deleterious	0.987	Probably Damaging	0.945	Probably Damaging	4.17	Benign	0.45	Tolerated			-1	-1	-2.6	-30.09
c.2327G>A	G776D 2D AIThe SynGAP1 missense variant G776D is catalogued in gnomAD (ID 6‑33442485‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates benign. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G776D, 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		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250				6-33442485-G-A			0.388	Likely Benign	0.566	Likely Pathogenic	Likely Benign	0.188	Likely Benign	0.1835	0.2971											0.16	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.30	Benign	0.10	Tolerated	3.64	6	-1	1	-3.1	58.04
c.352A>C	M118L 2D AIThe SynGAP1 missense variant M118L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. 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) also benign; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign effect for M118L, and this conclusion does not contradict any ClinVar status, as no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500							-1.319	Likely Benign	0.206	Likely Benign	Likely Benign	0.218	Likely Benign	0.1835	0.4511											-1.09	Neutral	0.000	Benign	0.001	Benign	4.11	Benign	0.03	Affected			4	2	1.9	-18.03
c.352A>T	M118L 2D AIThe SynGAP1 missense variant M118L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT indicates a pathogenic effect, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (derived from the four high‑accuracy tools) 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 points to a benign impact for M118L, 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		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500							-1.319	Likely Benign	0.206	Likely Benign	Likely Benign	0.218	Likely Benign	0.1835	0.4511											-1.09	Neutral	0.000	Benign	0.001	Benign	4.11	Benign	0.03	Affected			4	2	1.9	-18.03
c.4021G>A	A1341T 2D AIThe SynGAP1 missense variant A1341T is listed in ClinVar (ID 837815.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451895‑G‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or likely benign. Only SIFT predicts a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for A1341T, 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		0.823549	Disordered	0.980111	Binding	0.383	0.696	1.000	Conflicting		3	6-33451895-G-A	45	3.44e-5	-3.224	Likely Benign	0.081	Likely Benign	Likely Benign	0.099	Likely Benign	0.1835	0.7391											-0.58	Neutral	0.000	Benign	0.000	Benign	4.09	Benign	0.03	Affected	3.77	5	1	0	-2.5	30.03
c.1569C>A	N523K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include FoldX and Foldetta, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. Uncertain results are reported only by Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Taken together, the preponderance of evidence supports a pathogenic classification for this variant, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125							-12.276	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.607	Likely Pathogenic	0.1837	0.2866		-0.17	Likely Benign	0.2	-0.58	Ambiguous	-0.38	Likely Benign	0.73	Ambiguous	-5.35	Deleterious	0.972	Probably Damaging	0.728	Possibly Damaging	-1.30	Pathogenic	0.04	Affected			1	0	-0.4	14.07
c.1569C>G	N523K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N523K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include FoldX and Foldetta, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. Uncertain results are reported only by Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Taken together, the preponderance of evidence supports a pathogenic classification for this variant, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.033426	Uncertain	0.883	0.383	0.125							-12.276	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.607	Likely Pathogenic	0.1837	0.2866		-0.17	Likely Benign	0.2	-0.58	Ambiguous	-0.38	Likely Benign	0.73	Ambiguous	-5.35	Deleterious	0.972	Probably Damaging	0.728	Possibly Damaging	-1.30	Pathogenic	0.04	Affected			1	0	-0.4	14.07
c.2819G>A	G940D 2D AIThe SynGAP1 missense variant G940D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443371‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Two tools, AlphaMissense‑Default and ESM1b, 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 receives two benign and two uncertain votes, and Foldetta’s protein‑folding stability analysis is unavailable. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.889439	Disordered	0.920635	Binding	0.383	0.902	0.625				6-33443371-G-A	6	3.72e-6	-7.311	In-Between	0.397	Ambiguous	Likely Benign	0.076	Likely Benign	0.1837	0.2252											-0.68	Neutral	0.770	Possibly Damaging	0.583	Possibly Damaging	2.72	Benign	0.17	Tolerated	3.77	5	-1	1	-3.1	58.04
c.830A>C	K277T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K277T missense variant is not reported in ClinVar (status: None) and has no entry in gnomAD. Prediction tools that agree on a benign effect are Rosetta and premPS, while the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. FoldX and Foldetta return uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; Foldetta remains uncertain. Overall, the preponderance of evidence indicates that K277T 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	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250							-11.688	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.573	Likely Pathogenic	0.1837	0.2220		1.46	Ambiguous	0.1	0.14	Likely Benign	0.80	Ambiguous	0.17	Likely Benign	-5.52	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.02	Pathogenic	0.01	Affected			0	-1	3.2	-27.07
c.2078A>G	H693R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of algorithms (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect, and Foldetta’s stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000							-14.326	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.593	Likely Pathogenic	0.1839	0.1670		1.39	Ambiguous	0.2	1.28	Ambiguous	1.34	Ambiguous	1.03	Destabilizing	-7.97	Deleterious	0.998	Probably Damaging	0.646	Possibly Damaging	3.13	Benign	0.01	Affected			2	0	-1.3	19.05
c.3962C>A	P1321Q 2D AIThe SynGAP1 missense variant P1321Q is listed in ClinVar (ID 833687.0) as benign and is present in gnomAD (variant ID 6‑33451836‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification, and AlphaMissense‑Optimized also reports 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‑confidence SGM consensus and AlphaMissense‑Optimized—supports a benign impact. This conclusion aligns with the ClinVar benign status, with no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.933505	Binding	0.463	0.828	0.875	Benign		1	6-33451836-C-A	1	6.58e-7	-5.594	Likely Benign	0.079	Likely Benign	Likely Benign	0.055	Likely Benign	0.1839	0.4884											-0.74	Neutral	0.659	Possibly Damaging	0.034	Benign	4.24	Benign	0.09	Tolerated	3.77	5	0	-1	-1.9	31.01
c.955G>C	A319P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A319P is catalogued in gnomAD (ID 6‑33437860‑G‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Predictions that are inconclusive are Rosetta, ESM1b, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect, 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.		C2	0.179055	Structured	0.410405	Uncertain	0.879	0.254	0.125				6-33437860-G-C	3	1.86e-6	-7.213	In-Between	0.109	Likely Benign	Likely Benign	0.286	Likely Benign	0.1839	0.5067		-0.02	Likely Benign	0.9	-1.18	Ambiguous	-0.60	Ambiguous	0.22	Likely Benign	0.11	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	1.97	Pathogenic	1.00	Tolerated	3.38	23	-1	1	-3.4	26.04
c.998A>C	K333T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K333T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, and SIFT, whereas a larger set—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score—predict a pathogenic impact. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) reports a benign effect. Overall, the majority of evidence points to a pathogenic effect for K333T, and this conclusion does not conflict with any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500							-11.358	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	0.506	Likely Pathogenic	0.1839	0.3354		0.51	Ambiguous	0.0	-0.15	Likely Benign	0.18	Likely Benign	0.46	Likely Benign	-4.82	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.96	Pathogenic	0.08	Tolerated			0	-1	3.2	-27.07
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	0.533	Likely Pathogenic	0.1841	0.2030		3.06	Destabilizing	0.1	5.13	Destabilizing	4.10	Destabilizing	1.07	Destabilizing	-6.74	Deleterious	0.991	Probably Damaging	0.985	Probably Damaging	3.44	Benign	0.04	Affected			-1	-1	1.4	-48.04
c.2182C>A	P728T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728T has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, while the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P728T, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625							-9.605	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	0.298	Likely Benign	0.1843	0.3917		1.06	Ambiguous	0.0	1.27	Ambiguous	1.17	Ambiguous	0.62	Ambiguous	-6.21	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	0.67	Pathogenic	0.00	Affected			0	-1	0.9	3.99
c.1166C>T	S389L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S389L is catalogued in gnomAD (6‑33438071‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM‑Consensus score (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments are consistent with the benign consensus: AlphaMissense‑Optimized reports Benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts 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 conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.703578	Disordered	0.417444	Uncertain	0.306	0.803	0.875				6-33438071-C-T	7	4.40e-6	-6.040	Likely Benign	0.165	Likely Benign	Likely Benign	0.456	Likely Benign	0.1844	0.5871		0.04	Likely Benign	0.1	0.69	Ambiguous	0.37	Likely Benign	-0.23	Likely Benign	-0.75	Neutral	0.462	Possibly Damaging	0.693	Possibly Damaging	5.05	Benign	0.01	Affected	4.32	8	-2	-3	4.6	26.08
c.1987T>G	F663V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all indicate pathogenicity, while only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000							-14.196	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.655	Likely Pathogenic	0.1844	0.1983		3.04	Destabilizing	0.1	3.31	Destabilizing	3.18	Destabilizing	1.75	Destabilizing	-6.98	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	3.02	Benign	0.00	Affected			-1	-1	1.4	-48.04
c.3412T>A	S1138T 2D AIThe SynGAP1 missense variant S1138T 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 S1138T, 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		0.891961	Disordered	0.738250	Binding	0.346	0.869	1.000							-5.243	Likely Benign	0.081	Likely Benign	Likely Benign	0.370	Likely Benign	0.1844	0.6653											-1.21	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	5.45	Benign	0.23	Tolerated			1	1	0.1	14.03
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	0.817	Likely Pathogenic	0.1844	0.1949		1.00	Ambiguous	0.3	1.86	Ambiguous	1.43	Ambiguous	1.40	Destabilizing	-4.20	Deleterious	0.991	Probably Damaging	0.999	Probably Damaging	5.76	Benign	0.00	Affected			-1	-3	-4.6	-42.08
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	0.1845	0.4941											-1.88	Neutral	0.984	Probably Damaging	0.855	Possibly Damaging	2.64	Benign	0.05	Affected			1	-1	-3.4	26.04
c.2350G>C	A784P 2D AIThe SynGAP1 missense variant A784P is reported in gnomAD (variant ID 6-33442902‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact for A784P. 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		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625				6-33442902-G-C	4	2.48e-6	-3.777	Likely Benign	0.154	Likely Benign	Likely Benign	0.189	Likely Benign	0.1846	0.4771											-0.73	Neutral	0.586	Possibly Damaging	0.396	Benign	2.66	Benign	0.19	Tolerated	3.64	6	-1	1	-3.4	26.04
c.3695A>C	K1232T 2D AIThe SynGAP1 missense variant K1232T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125							-9.276	Likely Pathogenic	0.568	Likely Pathogenic	Likely Benign	0.189	Likely Benign	0.1846	0.3196											-4.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0	-1	3.2	-27.07
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	0.1846	0.4427											-1.13	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	4.10	Benign	0.08	Tolerated	3.54	6	1	1	-2.6	16.00
c.701G>T	R234L 2D AIThe SynGAP1 missense variant R234L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy methods show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions (7 pathogenic vs. 4 benign) and the pathogenic consensus from the high‑accuracy SGM‑Consensus suggest that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.311558	Uncertain	0.804	0.322	0.000							-11.153	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	0.734	Likely Pathogenic	0.1846	0.4783		1.38	Ambiguous	0.9	0.50	Ambiguous	0.94	Ambiguous	0.20	Likely Benign	-4.64	Deleterious	0.649	Possibly Damaging	0.199	Benign	5.78	Benign	0.11	Tolerated			-3	-2	8.3	-43.03
c.1195G>C	A399P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A399P 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, PROVEAN, SIFT, FATHMM, and polyPhen‑2 HumVar; pathogenic predictions come from FoldX, Rosetta, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and Foldetta. 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 pathogenic effect. Overall, the majority of evidence points toward a deleterious impact. The variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.394753	Structured	0.407674	Uncertain	0.939	0.490	0.125							-8.809	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	0.498	Likely Benign	0.1847	0.5472		2.29	Destabilizing	0.1	4.00	Destabilizing	3.15	Destabilizing	0.74	Ambiguous	-1.82	Neutral	0.596	Possibly Damaging	0.188	Benign	5.56	Benign	0.10	Tolerated			1	-1	-3.4	26.04
c.359G>A	G120D 2D AIThe SynGAP1 missense variant G120D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus, SGM‑Consensus, 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 evidence overwhelmingly supports 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.	Likely Benign		0.707965	Disordered	0.659993	Binding	0.359	0.887	0.750							-3.483	Likely Benign	0.465	Ambiguous	Likely Benign	0.037	Likely Benign	0.1847	0.2024											-0.57	Neutral	0.165	Benign	0.034	Benign	4.25	Benign	0.21	Tolerated			1	-1	-3.1	58.04
c.1942T>G	F648V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include SIFT and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus—predict it to be pathogenic. High‑accuracy methods give consistent results: AlphaMissense‑Optimized indicates pathogenicity; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a destabilizing, pathogenic effect. No prediction is missing or inconclusive. Overall, the evidence overwhelmingly supports a pathogenic classification, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000							-11.574	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.514	Likely Pathogenic	0.1848	0.1983		3.11	Destabilizing	0.1	2.80	Destabilizing	2.96	Destabilizing	1.14	Destabilizing	-6.98	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	3.49	Benign	0.06	Tolerated			-1	-1	1.4	-48.04
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	0.1848	0.3335											-1.65	Neutral	0.990	Probably Damaging	0.921	Probably Damaging	2.60	Benign	0.02	Affected			0	-1	3.2	-27.07
c.2773C>G	L925V 2D AIThe SynGAP1 missense variant L925V is not 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, has no available result for this variant. Overall, the majority of consensus tools predict a pathogenic impact, and this prediction does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.483068	Structured	0.977963	Binding	0.290	0.852	0.125							-3.977	Likely Benign	0.831	Likely Pathogenic	Ambiguous	0.244	Likely Benign	0.1848	0.3230											-2.09	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.36	Pathogenic	0.00	Affected			2	1	0.4	-14.03
c.329T>A	V110D 2D AIThe SynGAP1 missense variant V110D is not 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 pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate a pathogenic effect. This prediction is consistent with the lack of ClinVar reporting and does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.665934	Binding	0.347	0.860	0.750							-4.536	Likely Benign	0.970	Likely Pathogenic	Likely Pathogenic	0.189	Likely Benign	0.1849	0.1115											-2.84	Deleterious	0.978	Probably Damaging	0.500	Possibly Damaging	4.04	Benign	0.00	Affected			-2	-3	-7.7	15.96
c.1594A>C	T532P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T532P is listed in ClinVar as Benign (ClinVar ID 1598909.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus, and Foldetta (combining FoldX‑MD and Rosetta outputs)—all 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 is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.275179	Structured	0.021478	Uncertain	0.889	0.385	0.000	Benign		1				-2.143	Likely Benign	0.061	Likely Benign	Likely Benign	0.201	Likely Benign	0.1850	0.3811		-0.30	Likely Benign	0.2	0.06	Likely Benign	-0.12	Likely Benign	0.08	Likely Benign	-0.90	Neutral	0.005	Benign	0.008	Benign	-1.28	Pathogenic	0.18	Tolerated	3.37	35	0	-1	-0.9	-3.99	174.2	35.1	0.4	0.0	0.1	0.0						X		Potentially Benign	Thr532 is located on an α-α loop between the two α-helices (res. Gly502-Tyr518 and Ala533-Val560) facing the membrane. In the WT simulations, the hydroxyl group of Thr532 occasionally forms hydrogen bonds with the backbone atoms of other loop residues without any specific interaction. In the variant simulations, the Pro532 residue swap does not cause structural changes. Although hydrophilic residues seem more favorable in the loop, the pyrrolidine side chain of proline is well suited for unstructured protein regions such as loops. However, due to its location at the SynGAP-membrane interface, the effect of the residue swap cannot be fully addressed using the SynGAP solvent-only simulations.
c.3056G>T	R1019L 2D AIThe SynGAP1 missense variant R1019L is listed in ClinVar with an “Uncertain” status (ClinVar ID 3364537.0) and is present in gnomAD (gnomAD ID 6‑33443608‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.856457	Disordered	0.966400	Binding	0.315	0.794	0.500	Uncertain		1	6-33443608-G-T	2	1.24e-6	-5.194	Likely Benign	0.752	Likely Pathogenic	Likely Benign	0.110	Likely Benign	0.1850	0.4886											-3.57	Deleterious	0.800	Possibly Damaging	0.573	Possibly Damaging	2.40	Pathogenic	0.01	Affected	3.77	5	-2	-3	8.3	-43.03
c.472C>A	Q158K 2D AIThe SynGAP1 missense variant Q158K is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. 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 interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the computational evidence strongly suggests 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		0.480142	Structured	0.527565	Binding	0.286	0.750	0.375							-6.795	Likely Benign	0.481	Ambiguous	Likely Benign	0.069	Likely Benign	0.1851	0.3869											-0.86	Neutral	0.276	Benign	0.121	Benign	4.20	Benign	0.15	Tolerated			1	1	-0.4	0.04
c.3520G>A	E1174K 2D AIThe SynGAP1 missense variant E1174K is listed in ClinVar with an uncertain significance (ClinVar ID 1905754.0) and is present in gnomAD (variant ID 6‑33444555‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification, matching the reported SGM‑Consensus result. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Taken together, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.483068	Structured	0.618958	Binding	0.523	0.734	0.375	Uncertain		1	6-33444555-G-A	2	1.24e-6	-4.345	Likely Benign	0.898	Likely Pathogenic	Ambiguous	0.442	Likely Benign	0.1852	0.6521											-1.59	Neutral	0.962	Probably Damaging	0.367	Benign	5.52	Benign	0.03	Affected	4.32	2	0	1	-0.4	-0.94
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	0.478	Likely Benign	0.1853	0.3024		0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			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	0.268	Likely Benign	0.1853	0.3024		0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			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	0.268	Likely Benign	0.1853	0.3024		0.88	Ambiguous	0.1	0.69	Ambiguous	0.79	Ambiguous	0.71	Ambiguous	-5.78	Deleterious	0.994	Probably Damaging	0.952	Probably Damaging	3.60	Benign	0.22	Tolerated			2	0	1.0	-34.02
c.1641T>G	C547W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547W is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic, while premPS remains uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenic. Taken together, the overwhelming consensus from both general and high‑accuracy predictors is that C547W 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	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000							-15.788	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.764	Likely Pathogenic	0.1854	0.2750		11.03	Destabilizing	0.3	2.63	Destabilizing	6.83	Destabilizing	0.54	Ambiguous	-10.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.34	Pathogenic	0.01	Affected			-8	-2	-3.4	83.07
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	0.322	Likely Benign	0.1854	0.3386		0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	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	0.322	Likely Benign	0.1854	0.3386		0.12	Likely Benign	0.1	0.80	Ambiguous	0.46	Likely Benign	0.07	Likely Benign	-0.01	Neutral	0.994	Probably Damaging	0.979	Probably Damaging	-1.35	Pathogenic	0.88	Tolerated	3.37	35	2	3	0.0	-14.03
c.3079A>G	N1027D 2D AIThe SynGAP1 missense variant N1027D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, and AlphaMissense‑Default remains uncertain. High‑accuracy tools reinforce the benign assessment: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500							-2.891	Likely Benign	0.458	Ambiguous	Likely Benign	0.073	Likely Benign	0.1854	0.4004											-1.27	Neutral	0.649	Possibly Damaging	0.353	Benign	2.74	Benign	0.27	Tolerated			2	1	0.0	0.98
c.1638C>G	C546W 2D 3DClick to see structure in 3D Viewer AIClinVar has no entry for this SynGAP1 missense variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, which scores the substitution as tolerated. The majority of other in silico predictors classify the change as pathogenic: REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) report a likely pathogenic outcome. Predictions that are inconclusive or unavailable are FoldX, Foldetta, and premPS. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, while Foldetta’s stability analysis is uncertain. Overall, the consensus of the available evidence points to a pathogenic effect for the variant, and this conclusion does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000							-14.685	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.703	Likely Pathogenic	0.1855	0.2904		-0.79	Ambiguous	1.2	3.60	Destabilizing	1.41	Ambiguous	0.56	Ambiguous	-9.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.24	Pathogenic	0.08	Tolerated			-8	-2	-3.4	83.07
c.2555G>A	G852D 2D AIThe SynGAP1 missense variant G852D is catalogued in gnomAD (ID 6‑33443107‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while the single pathogenic signal comes from 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 reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for G852D, and this conclusion is not contradicted by any ClinVar annotation (none is present). 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				6-33443107-G-A	1	6.20e-7	-5.588	Likely Benign	0.203	Likely Benign	Likely Benign	0.154	Likely Benign	0.1855	0.2175											0.67	Neutral	0.001	Benign	0.005	Benign	4.18	Benign	0.01	Affected	3.77	5	-1	1	-3.1	58.04
c.577G>C	A193P 2D AIThe SynGAP1 missense variant A193P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also yields a pathogenic consensus. 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 indicates that A193P 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.			0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125							-7.293	In-Between	0.986	Likely Pathogenic	Likely Pathogenic	0.267	Likely Benign	0.1855	0.5601											-2.70	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.99	Benign	0.05	Affected			1	-1	-3.4	26.04
c.2207G>T	R736L 2D AIThe SynGAP1 missense variant R736L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign classification, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.415259	Uncertain	0.305	0.771	0.875							-4.173	Likely Benign	0.133	Likely Benign	Likely Benign	0.061	Likely Benign	0.1856	0.3180											-1.27	Neutral	0.653	Possibly Damaging	0.361	Benign	2.60	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.3112A>C	T1038P 2D AIThe SynGAP1 missense variant T1038P is not 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 remains uncertain, and 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 is present). 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							-2.196	Likely Benign	0.390	Ambiguous	Likely Benign	0.116	Likely Benign	0.1856	0.4680											-1.10	Neutral	0.965	Probably Damaging	0.611	Possibly Damaging	2.66	Benign	0.26	Tolerated			0	-1	-0.9	-3.99
c.3169A>T	S1057C 2D AIThe SynGAP1 missense variant S1057C is reported in gnomAD (ID 6‑33443721‑A‑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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Two tools, polyPhen‑2 HumDiv and polyPhen‑2 HumVar, predict a pathogenic impact, while ESM1b is 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 effect, 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		0.988291	Disordered	0.869507	Binding	0.413	0.927	0.875				6-33443721-A-T			-7.529	In-Between	0.100	Likely Benign	Likely Benign	0.258	Likely Benign	0.1856	0.6106											-0.64	Neutral	0.977	Probably Damaging	0.683	Possibly Damaging	5.23	Benign	0.10	Tolerated	3.77	5	-1	0	3.3	16.06
c.99A>C	Q33H 2D AIThe SynGAP1 missense variant Q33H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.436712	Uncertain	0.342	0.860	0.375							-0.450	Likely Benign	0.133	Likely Benign	Likely Benign	0.054	Likely Benign	0.1856	0.4509											-0.95	Neutral	0.704	Possibly Damaging	0.198	Benign	4.16	Benign	0.00	Affected			3	0	0.3	9.01
c.99A>T	Q33H 2D AIThe SynGAP1 missense variant Q33H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.436712	Uncertain	0.342	0.860	0.375							-0.450	Likely Benign	0.133	Likely Benign	Likely Benign	0.054	Likely Benign	0.1856	0.4509											-0.95	Neutral	0.704	Possibly Damaging	0.198	Benign	4.16	Benign	0.00	Affected			3	0	0.3	9.01
c.3133G>A	A1045T 2D AIThe SynGAP1 missense variant A1045T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.975609	Disordered	0.948874	Binding	0.352	0.882	0.750							-4.531	Likely Benign	0.074	Likely Benign	Likely Benign	0.059	Likely Benign	0.1857	0.6682											0.03	Neutral	0.004	Benign	0.010	Benign	2.68	Benign	0.52	Tolerated			1	0	-2.5	30.03
c.622C>A	P208T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208T missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta; premPS and Rosetta are uncertain. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta also predicts pathogenic. With the majority of tools, including the high‑accuracy ones, indicating pathogenicity, the variant is most likely pathogenic. This assessment 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	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125							-9.016	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign	0.270	Likely Benign	0.1857	0.5197		3.20	Destabilizing	0.5	1.27	Ambiguous	2.24	Destabilizing	0.94	Ambiguous	-6.80	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.76	Benign	0.01	Affected			0	-1	0.9	3.99
c.1379A>C	K460T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K460T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) yield uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD/Rosetta analysis remains inconclusive. Overall, the majority of evidence points to a pathogenic impact for K460T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125							-11.187	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.208	Likely Benign	0.1858	0.3848		1.23	Ambiguous	0.1	1.16	Ambiguous	1.20	Ambiguous	0.77	Ambiguous	-5.02	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.35	Benign	0.07	Tolerated			0	-1	3.2	-27.07
c.2410G>C	D804H 2D AIThe SynGAP1 D804H missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions suggests that D804H is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.801317	Disordered	0.786762	Binding	0.294	0.900	0.625							-5.100	Likely Benign	0.821	Likely Pathogenic	Ambiguous	0.296	Likely Benign	0.1859	0.7607											-3.79	Deleterious	0.999	Probably Damaging	0.975	Probably Damaging	1.19	Pathogenic	0.01	Affected			1	-1	0.3	22.05
c.2662G>C	A888P 2D AIThe SynGAP1 missense variant A888P is reported in gnomAD (variant ID 6‑33443214‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence supports a benign classification for A888P, 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		0.784345	Disordered	0.575860	Binding	0.352	0.928	0.625				6-33443214-G-C	5	3.10e-6	-2.368	Likely Benign	0.083	Likely Benign	Likely Benign	0.050	Likely Benign	0.1859	0.5764											-0.02	Neutral	0.000	Benign	0.000	Benign	2.56	Benign	0.00	Affected	4.32	4	-1	1	-3.4	26.04
c.3779A>C	K1260T 2D AIThe SynGAP1 missense variant K1260T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in‑silico tools indicates that K1260T is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250							-10.099	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign	0.387	Likely Benign	0.1859	0.3028											-4.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.33	Pathogenic	0.00	Affected			0	-1	3.2	-27.07
c.634T>C	S212P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S212P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX and FATHMM, whereas the remaining tools—REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic. High‑accuracy methods give consistent pathogenic results: AlphaMissense‑Optimized scores it as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. With the overwhelming majority of tools supporting pathogenicity and no ClinVar entry to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.158265	Structured	0.381517	Uncertain	0.846	0.278	0.125							-13.051	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.809	Likely Pathogenic	0.1859	0.5679		0.02	Likely Benign	0.9	6.30	Destabilizing	3.16	Destabilizing	0.90	Ambiguous	-4.13	Deleterious	0.995	Probably Damaging	0.979	Probably Damaging	5.75	Benign	0.01	Affected			1	-1	-0.8	10.04
c.2860C>A	P954T 2D AIThe SynGAP1 missense variant P954T is not 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 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		0.984159	Disordered	0.932268	Binding	0.465	0.926	0.750							-5.657	Likely Benign	0.072	Likely Benign	Likely Benign	0.089	Likely Benign	0.1860	0.6324											-0.77	Neutral	0.977	Probably Damaging	0.856	Possibly Damaging	2.79	Benign	0.48	Tolerated			0	-1	0.9	3.99
c.1208A>C	K403T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403T 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 limited to FATHMM, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; SGM‑Consensus predicts likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Other stability predictors (FoldX, Rosetta, premPS) are also uncertain. Overall, the consensus of the majority of tools indicates a pathogenic effect. This conclusion is not contradicted by ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000							-13.135	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.522	Likely Pathogenic	0.1861	0.4230		1.41	Ambiguous	0.1	0.59	Ambiguous	1.00	Ambiguous	0.67	Ambiguous	-5.43	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.73	Benign	0.01	Affected			0	-1	3.2	-27.07
c.3860C>T	P1287L 2D AIThe SynGAP1 missense variant P1287L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33447908‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.813701	Binding	0.538	0.777	0.750	Conflicting		2	6-33447908-C-T			-2.800	Likely Benign	0.117	Likely Benign	Likely Benign	0.061	Likely Benign	0.1861	0.4727											-1.66	Neutral	0.021	Benign	0.017	Benign	2.76	Benign	0.02	Affected	3.77	5	-3	-3	5.4	16.04
c.3952C>G	L1318V 2D AIThe SynGAP1 missense variant L1318V is catalogued in gnomAD (ID 6‑33451826‑C‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar record, which contains no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.968271	Binding	0.399	0.865	0.750				6-33451826-C-G	1	6.31e-7	-3.938	Likely Benign	0.091	Likely Benign	Likely Benign	0.038	Likely Benign	0.1861	0.3027											-0.58	Neutral	0.113	Benign	0.028	Benign	4.08	Benign	0.75	Tolerated	3.77	5	1	2	0.4	-14.03
c.496G>C	A166P 2D AIThe SynGAP1 missense variant A166P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for A166P, 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		0.425610	Structured	0.505037	Binding	0.384	0.658	0.125							-9.665	Likely Pathogenic	0.273	Likely Benign	Likely Benign	0.172	Likely Benign	0.1861	0.3668											-2.04	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	3.99	Benign	0.02	Affected			1	-1	-3.4	26.04
c.1051G>C	A351P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A351P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are Foldetta, PROVEAN, SIFT, FATHMM, and Rosetta. FoldX and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the lack of ClinVar reporting; thus the variant is most likely benign rather than pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000							-6.559	Likely Benign	0.147	Likely Benign	Likely Benign	0.051	Likely Benign	0.1862	0.5472		-0.89	Ambiguous	0.2	6.19	Destabilizing	2.65	Destabilizing	0.62	Ambiguous	-3.08	Deleterious	0.016	Benign	0.007	Benign	1.67	Pathogenic	0.03	Affected			1	-1	-3.4	26.04
c.3658G>A	E1220K 2D AIThe SynGAP1 missense variant E1220K is listed in gnomAD (6‑33446650‑G‑A) but has no ClinVar entry. Prediction tools that agree on benign impact include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that E1220K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375				6-33446650-G-A	1	6.20e-7	-12.478	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.415	Likely Benign	0.1862	0.4046											-3.46	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.63	Pathogenic	0.00	Affected	3.77	5	1	0	-0.4	-0.94
c.1340T>G	V447G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V447G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM, while the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that V447G is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000							-13.648	Likely Pathogenic	0.861	Likely Pathogenic	Ambiguous	0.499	Likely Benign	0.1863	0.2240		3.81	Destabilizing	0.1	4.62	Destabilizing	4.22	Destabilizing	2.28	Destabilizing	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.31	Benign	0.01	Affected			-1	-3	-4.6	-42.08
c.2698A>C	T900P 2D AIThe SynGAP1 missense variant T900P is not 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 (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 further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion 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		0.675549	Disordered	0.465347	Uncertain	0.289	0.924	0.375							-2.684	Likely Benign	0.084	Likely Benign	Likely Benign	0.067	Likely Benign	0.1863	0.4874											-0.40	Neutral	0.812	Possibly Damaging	0.473	Possibly Damaging	2.67	Benign	0.22	Tolerated			0	-1	-0.9	-3.99
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	0.1863	0.2402											-2.08	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.43	Benign	0.27	Tolerated			2	0	-1.3	19.05
c.3970C>A	P1324T 2D AIThe SynGAP1 missense variant P1324T is listed in gnomAD (ID 6‑33451844‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv and SIFT. 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 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 consensus of the available predictions points to a benign effect, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.899181	Binding	0.432	0.793	0.875				6-33451844-C-A			-5.289	Likely Benign	0.077	Likely Benign	Likely Benign	0.072	Likely Benign	0.1863	0.4761											0.95	Neutral	0.588	Possibly Damaging	0.175	Benign	4.43	Benign	0.00	Affected	4.32	1	-1	0	0.9	3.99
c.1258T>A	F420I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000							-12.567	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.330	Likely Benign	0.1864	0.2113		2.88	Destabilizing	0.0	3.64	Destabilizing	3.26	Destabilizing	1.25	Destabilizing	-5.46	Deleterious	0.575	Possibly Damaging	0.059	Benign	3.22	Benign	0.02	Affected			1	0	1.7	-34.02
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	0.1864	0.6227											-1.04	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.51	Benign	0.00	Affected			1	1	0.1	14.03
c.515G>C	R172P 2D AIThe SynGAP1 missense variant R172P has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (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, while Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375							-8.059	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	0.227	Likely Benign	0.1864	0.4312											-3.16	Deleterious	0.929	Possibly Damaging	0.519	Possibly Damaging	3.99	Benign	0.01	Affected			0	-2	2.9	-59.07
c.3220C>A	Q1074K 2D AIThe SynGAP1 missense variant Q1074K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.987006	Binding	0.339	0.897	0.750							-6.162	Likely Benign	0.712	Likely Pathogenic	Likely Benign	0.110	Likely Benign	0.1865	0.4600											-0.88	Neutral	0.011	Benign	0.006	Benign	2.75	Benign	0.36	Tolerated			1	1	-0.4	0.04
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	0.1865	0.7600											-0.65	Neutral	0.991	Probably Damaging	0.989	Probably Damaging	3.17	Benign	0.00	Affected			1	0	-2.5	30.03
c.1004G>C	R335P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R335P has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and SIFT, whereas pathogenic predictions are reported by FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments give a more focused view: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. Taken together, the majority of evidence points to a pathogenic impact for R335P, and 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	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500							-13.952	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.250	Likely Benign	0.1866	0.4497		3.23	Destabilizing	0.8	5.73	Destabilizing	4.48	Destabilizing	0.43	Likely Benign	-4.22	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.69	Pathogenic	0.09	Tolerated			0	-2	2.9	-59.07
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	0.1866	0.3706											-1.96	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.50	Benign	0.02	Affected			-1	-1	3.8	-55.08
c.4024G>A	D1342N 2D AIThe SynGAP1 missense variant D1342N is catalogued in gnomAD (ID 6‑33451898‑G‑A) but has no ClinVar submission. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated or benign. Grouping by consensus, all listed predictors fall into the benign category, with no tool reporting pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta stability analysis is unavailable for this variant. Consequently, the aggregate evidence strongly supports a benign classification, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.981682	Binding	0.316	0.678	0.875				6-33451898-G-A			-3.459	Likely Benign	0.140	Likely Benign	Likely Benign	0.058	Likely Benign	0.1868	0.6022											0.29	Neutral	0.000	Benign	0.002	Benign	4.07	Benign	0.93	Tolerated	4.32	4	1	2	0.0	-0.98
c.812C>G	A271G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A271G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or unavailable stability results and are not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as unavailable. Overall, the balance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125							-9.508	Likely Pathogenic	0.183	Likely Benign	Likely Benign	0.434	Likely Benign	0.1869	0.2388		1.73	Ambiguous	0.1	1.43	Ambiguous	1.58	Ambiguous	1.31	Destabilizing	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.89	Pathogenic	0.01	Affected			1	0	-2.2	-14.03
c.1626C>A	N542K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542K is not reported in ClinVar and has no entries in gnomAD. Prediction tools largely disagree: benign calls come from FoldX, SIFT, and Foldetta; pathogenic calls come from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (Rosetta and premPS) give uncertain results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, whereas Foldetta predicts benign. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence (nine pathogenic vs three benign) points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000							-11.967	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.610	Likely Pathogenic	0.1870	0.4349		-0.36	Likely Benign	0.1	0.53	Ambiguous	0.09	Likely Benign	0.75	Ambiguous	-5.33	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.23	Pathogenic	0.10	Tolerated			1	0	-0.4	14.07
c.1626C>G	N542K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542K 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 FoldX, SIFT, and Foldetta. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (Rosetta and premPS) returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also pathogenic, while Foldetta predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence (nine pathogenic vs. three benign) 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	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000							-11.967	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.610	Likely Pathogenic	0.1870	0.4349		-0.36	Likely Benign	0.1	0.53	Ambiguous	0.09	Likely Benign	0.75	Ambiguous	-5.33	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.23	Pathogenic	0.10	Tolerated			1	0	-0.4	14.07
c.3473T>G	V1158G 2D AIThe SynGAP1 missense variant V1158G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic outcome. High‑accuracy assessments reinforce this pattern: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that V1158G is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250							-3.058	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic	0.433	Likely Benign	0.1870	0.3289											-4.62	Deleterious	0.997	Probably Damaging	0.999	Probably Damaging	2.30	Pathogenic	0.00	Affected			-1	-3	-4.6	-42.08
c.1798C>A	P600T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P600T is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, Rosetta, and premPS. Those that predict pathogenicity are REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, while Foldetta indicates a benign effect on protein folding stability. Overall, the majority of computational evidence supports a pathogenic effect for P600T, 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	0.009728	Structured	0.162960	Uncertain	0.947	0.147	0.000							-11.945	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.737	Likely Pathogenic	0.1871	0.4954		2.61	Destabilizing	0.1	-2.90	Stabilizing	-0.15	Likely Benign	0.24	Likely Benign	-7.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.34	Pathogenic	0.01	Affected			0	-1	0.9	3.99
c.2843G>A	G948D 2D AIThe SynGAP1 missense variant G948D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988505	Disordered	0.862121	Binding	0.365	0.919	0.750							-8.423	Likely Pathogenic	0.267	Likely Benign	Likely Benign	0.279	Likely Benign	0.1871	0.2826											0.15	Neutral	0.818	Possibly Damaging	0.266	Benign	4.55	Benign	0.11	Tolerated			1	-1	-3.1	58.04
c.3595G>A	E1199K 2D AIThe SynGAP1 missense variant E1199K (ClinVar ID 1026146.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33446587‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are not available. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar Uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250	Uncertain		1	6-33446587-G-A	1	6.20e-7	-10.853	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	0.171	Likely Benign	0.1871	0.4072											-2.26	Neutral	1.000	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected	3.77	5	0	1	-0.4	-0.94
c.1771G>C	A591P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A591P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely converge on a pathogenic effect: pathogenic predictions come from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). Benign predictions are limited to REVEL and FATHMM. High‑accuracy assessments reinforce the pathogenic view: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenic. Consequently, the variant is most likely pathogenic, a conclusion that contrasts with its ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000	Uncertain		1				-14.479	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.404	Likely Benign	0.1872	0.3087		3.78	Destabilizing	0.3	7.29	Destabilizing	5.54	Destabilizing	1.45	Destabilizing	-4.41	Deleterious	0.995	Probably Damaging	0.853	Possibly Damaging	3.35	Benign	0.01	Affected	3.37	35	1	-1	-3.4	26.04	191.5	-10.1	0.2	0.1	0.4	0.1	X							Potentially Pathogenic	The methyl group of the Ala591 side chain, located in the middle of an α helix (res. Glu582-Met603), packs against hydrophobic residues (e.g., Ile483, Phe484) of an opposing partially helical loop (res. Phe476-Asn487).In the variant simulations, Pro591 lacks a free backbone amide group and, therefore, cannot form a hydrogen bond with the backbone carbonyl of Arg587 as Ala591 does in the WT. This notably weakens the α helix integrity and compromises the continuity of the helix. In reality, the effect on the structure during protein folding could be more severe.
c.3089A>C	H1030P 2D AIThe SynGAP1 missense variant H1030P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that H1030P is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.849326	Disordered	0.995856	Binding	0.375	0.735	0.500							-2.185	Likely Benign	0.148	Likely Benign	Likely Benign	0.154	Likely Benign	0.1872	0.4225											-0.78	Neutral	0.812	Possibly Damaging	0.298	Benign	2.77	Benign	0.02	Affected			0	-2	1.6	-40.02
c.3089A>G	H1030R 2D AIThe SynGAP1 missense variant H1030R is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.849326	Disordered	0.995856	Binding	0.375	0.735	0.500							-2.312	Likely Benign	0.340	Likely Benign	Likely Benign	0.031	Likely Benign	0.1872	0.2955											-1.08	Neutral	0.224	Benign	0.066	Benign	2.85	Benign	0.06	Tolerated			2	0	-1.3	19.05
c.3152G>A	G1051D 2D AISynGAP1 missense variant G1051D is listed in ClinVar as Benign and is present in gnomAD (variant ID 6‑33443704‑G‑A). Prediction tools that classify the variant as benign include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict pathogenicity are polyPhen‑2 HumDiv, ESM1b, and FATHMM. 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 (two benign versus two pathogenic votes), and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign effect, consistent with the ClinVar annotation and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.900141	Binding	0.358	0.936	0.875	Benign		1	6-33443704-G-A	2	1.24e-6	-9.379	Likely Pathogenic	0.311	Likely Benign	Likely Benign	0.445	Likely Benign	0.1872	0.2235											-0.31	Neutral	0.761	Possibly Damaging	0.239	Benign	-0.74	Pathogenic	0.39	Tolerated	3.77	5	-1	1	-3.1	58.04
c.3338G>A	G1113D 2D AIThe SynGAP1 missense variant G1113D is listed in ClinVar with an uncertain significance (ClinVar ID 2766136.0) and is present in gnomAD (variant ID 6‑33443890‑G‑A). Functional prediction tools that agree on a benign outcome include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all of which classify the substitution as benign. AlphaMissense‑Optimized also predicts a benign effect, whereas AlphaMissense‑Default remains uncertain. No tool predicts a pathogenic effect. The high‑accuracy consensus methods reinforce this benign assessment: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and AlphaMissense‑Optimized also indicates benign. Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective evidence strongly supports a benign impact, and this conclusion does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.905695	Disordered	0.900456	Binding	0.327	0.910	0.875	Uncertain		1	6-33443890-G-A			-4.638	Likely Benign	0.354	Ambiguous	Likely Benign	0.061	Likely Benign	0.1872	0.2452											-0.72	Neutral	0.029	Benign	0.017	Benign	2.58	Benign	0.34	Tolerated	4.32	2	-1	1	-3.1	58.04
c.646C>G	Q216E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv 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 benign, and Foldetta as benign. No predictions or stability results are missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000							-9.215	Likely Pathogenic	0.550	Ambiguous	Likely Benign	0.474	Likely Benign	0.1872	0.3117		0.49	Likely Benign	0.3	0.30	Likely Benign	0.40	Likely Benign	0.35	Likely Benign	-1.89	Neutral	0.779	Possibly Damaging	0.351	Benign	5.85	Benign	0.13	Tolerated			2	2	0.0	0.98
c.3411T>A	H1137Q 2D AIThe SynGAP1 missense variant H1137Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized scores benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and 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 computational 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		0.903857	Disordered	0.756488	Binding	0.314	0.879	0.875							-2.958	Likely Benign	0.110	Likely Benign	Likely Benign	0.239	Likely Benign	0.1873	0.4090											-1.19	Neutral	0.925	Possibly Damaging	0.703	Possibly Damaging	5.34	Benign	0.00	Affected			3	0	-0.3	-9.01
c.3411T>G	H1137Q 2D AIThe SynGAP1 missense variant H1137Q 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 H1137Q, and 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	0.756488	Binding	0.314	0.879	0.875							-2.958	Likely Benign	0.110	Likely Benign	Likely Benign	0.239	Likely Benign	0.1873	0.4090											-1.19	Neutral	0.925	Possibly Damaging	0.703	Possibly Damaging	5.34	Benign	0.00	Affected			3	0	-0.3	-9.01
c.2849G>A	G950D 2D AIThe SynGAP1 missense variant G950D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.888649	Binding	0.368	0.923	0.750							-7.515	In-Between	0.245	Likely Benign	Likely Benign	0.402	Likely Benign	0.1874	0.2826											-0.61	Neutral	0.411	Benign	0.131	Benign	2.26	Pathogenic	0.02	Affected			1	-1	-3.1	58.04
c.3280T>A	S1094T 2D AIThe SynGAP1 missense variant S1094T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods 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		0.938133	Disordered	0.981352	Binding	0.358	0.877	1.000							-4.009	Likely Benign	0.194	Likely Benign	Likely Benign	0.077	Likely Benign	0.1874	0.6902											-0.57	Neutral	0.790	Possibly Damaging	0.433	Benign	2.59	Benign	0.16	Tolerated			1	1	0.1	14.03
c.82T>A	S28T 2D AIThe SynGAP1 missense variant S28T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.438157	Uncertain	0.354	0.884	0.125							-3.810	Likely Benign	0.081	Likely Benign	Likely Benign	0.054	Likely Benign	0.1874	0.6140											-0.21	Neutral	0.000	Benign	0.000	Benign	4.20	Benign	0.64	Tolerated			1	1	0.1	14.03
c.917T>G	V306G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V306G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.363090	Structured	0.315026	Uncertain	0.896	0.287	0.125							-12.313	Likely Pathogenic	0.795	Likely Pathogenic	Ambiguous	0.529	Likely Pathogenic	0.1874	0.2035		4.39	Destabilizing	0.2	5.89	Destabilizing	5.14	Destabilizing	2.46	Destabilizing	-5.48	Deleterious	0.998	Probably Damaging	1.000	Probably Damaging	1.78	Pathogenic	0.00	Affected			-1	-3	-4.6	-42.08
c.2561G>T	R854L 2D AIThe SynGAP1 missense variant R854L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for R854L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750							-2.573	Likely Benign	0.167	Likely Benign	Likely Benign	0.131	Likely Benign	0.1875	0.5223											-1.78	Neutral	0.960	Probably Damaging	0.765	Possibly Damaging	4.11	Benign	0.03	Affected			-3	-2	8.3	-43.03
c.2566A>G	N856D 2D AIThe SynGAP1 missense variant N856D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (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 (majority vote) 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 multiple prediction algorithms and consensus analyses indicates that the variant is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500							-4.636	Likely Benign	0.195	Likely Benign	Likely Benign	0.091	Likely Benign	0.1875	0.4895											-1.25	Neutral	0.965	Probably Damaging	0.721	Possibly Damaging	4.17	Benign	0.61	Tolerated			2	1	0.0	0.98
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	0.362	Likely Benign	0.1876	0.2197		0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			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	0.362	Likely Benign	0.1876	0.2197		0.78	Ambiguous	0.6	-0.55	Ambiguous	0.12	Likely Benign	1.00	Destabilizing	-2.98	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.90	Benign	0.00	Affected			3	2	0.0	-14.03
c.2669G>T	R890L 2D AIThe SynGAP1 missense variant R890L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign prediction (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy and consensus predictions indicate a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625							-2.387	Likely Benign	0.389	Ambiguous	Likely Benign	0.213	Likely Benign	0.1876	0.3406											-2.74	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	3.98	Benign	0.20	Tolerated			-3	-2	8.3	-43.03
c.3229A>C	T1077P 2D AIThe SynGAP1 missense variant T1077P 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, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence shows AlphaMissense‑Optimized classifying the variant as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely benign outcome, and Foldetta results are unavailable. Overall, the majority of predictions and the high‑accuracy consensus point to a benign impact. This conclusion is not contradicted by ClinVar status, which has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.988141	Binding	0.329	0.892	0.750							-2.436	Likely Benign	0.345	Ambiguous	Likely Benign	0.164	Likely Benign	0.1876	0.4788											-0.91	Neutral	0.970	Probably Damaging	0.787	Possibly Damaging	4.16	Benign	0.04	Affected			0	-1	-0.9	-3.99
c.362C>A	A121D 2D AIThe SynGAP1 missense variant A121D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, 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		0.779859	Disordered	0.661304	Binding	0.362	0.888	0.750							-3.626	Likely Benign	0.595	Likely Pathogenic	Likely Benign	0.096	Likely Benign	0.1876	0.1945											-0.89	Neutral	0.244	Benign	0.050	Benign	4.06	Benign	0.03	Affected			0	-2	-5.3	44.01
c.2105A>C	Q702P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; FoldX is uncertain and therefore not counted. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, more tools predict pathogenicity (7) than benignity (5), and the high‑accuracy pathogenic prediction from Foldetta further supports this. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000							-10.361	Likely Pathogenic	0.324	Likely Benign	Likely Benign	0.369	Likely Benign	0.1877	0.3371		1.76	Ambiguous	0.1	7.05	Destabilizing	4.41	Destabilizing	-0.04	Likely Benign	-4.71	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.42	Benign	0.05	Affected			0	-1	1.9	-31.01
c.3188G>A	G1063D 2D AIThe SynGAP1 missense variant G1063D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the computational evidence overwhelmingly supports a benign impact for G1063D, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.975134	Disordered	0.945784	Binding	0.394	0.913	0.875							-6.950	Likely Benign	0.367	Ambiguous	Likely Benign	0.057	Likely Benign	0.1878	0.3026											-0.30	Neutral	0.411	Benign	0.058	Benign	4.24	Benign	0.08	Tolerated			1	-1	-3.1	58.04
c.3241G>C	A1081P 2D AIThe SynGAP1 missense variant A1081P is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.979759	Binding	0.288	0.895	0.750							-2.967	Likely Benign	0.178	Likely Benign	Likely Benign	0.051	Likely Benign	0.1878	0.4540											-1.07	Neutral	0.005	Benign	0.010	Benign	4.00	Benign	0.14	Tolerated			1	-1	-3.4	26.04
c.3848C>T	P1283L 2D AIThe SynGAP1 missense variant P1283L is listed in ClinVar (ID 536994.0) as Benign and is present in gnomAD (gnomAD ID 6‑33447896‑C‑T). All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic prediction. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts Benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, aligning with the ClinVar benign classification. 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	Benign		1	6-33447896-C-T	32	2.06e-5	-3.740	Likely Benign	0.093	Likely Benign	Likely Benign	0.047	Likely Benign	0.1878	0.4716											-1.04	Neutral	0.005	Benign	0.003	Benign	2.76	Benign	0.06	Tolerated	3.77	5	-3	-3	5.4	16.04
c.1286G>C	R429P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and ESM1b; AlphaMissense‑Default and FoldX are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools and the high‑accuracy methods favor a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000							-9.771	Likely Pathogenic	0.556	Ambiguous	Likely Benign	0.265	Likely Benign	0.1881	0.3790		1.53	Ambiguous	0.2	5.13	Destabilizing	3.33	Destabilizing	1.01	Destabilizing	-2.89	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.25	Tolerated			0	-2	2.9	-59.07
c.443C>A	P148H 2D AIThe SynGAP1 missense variant P148H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for P148H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625							-11.034	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.169	Likely Benign	0.1881	0.3847											-3.21	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.90	Benign	0.00	Affected			0	-2	-1.6	40.02
c.1532G>A	G511E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000							-12.263	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.479	Likely Benign	0.1882	0.4240		2.17	Destabilizing	0.2	2.62	Destabilizing	2.40	Destabilizing	1.15	Destabilizing	-7.69	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.24	Benign	0.02	Affected			0	-2	-3.1	72.06
c.1619A>C	Q540P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic, while premPS is uncertain. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a pathogenic effect. No tool predicts a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000							-16.096	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.922	Likely Pathogenic	0.1882	0.3654		3.95	Destabilizing	0.3	10.06	Destabilizing	7.01	Destabilizing	0.73	Ambiguous	-5.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.32	Pathogenic	0.01	Affected			0	-1	1.9	-31.01
c.1808T>C	M603T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M603T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that provide a clear verdict all classify the substitution as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool in the dataset reports a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus indicates likely pathogenic, while the Foldetta stability analysis is inconclusive and therefore not considered evidence. No contradictory evidence is present in ClinVar. Consequently, the variant is most likely pathogenic based on the available predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-13.152	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.903	Likely Pathogenic	0.1883	0.1495		1.71	Ambiguous	0.2	1.71	Ambiguous	1.71	Ambiguous	0.66	Ambiguous	-5.48	Deleterious	0.996	Probably Damaging	0.985	Probably Damaging	-1.29	Pathogenic	0.00	Affected			-1	-1	-2.6	-30.09
c.237C>A	N79K 2D AIThe SynGAP1 missense variant N79K is listed in gnomAD (ID 6‑33425845‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized scores benign and the SGM‑Consensus indicates “Likely Benign.” No Foldetta stability prediction 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 status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375				6-33425845-C-A	1	6.20e-7	-2.811	Likely Benign	0.422	Ambiguous	Likely Benign	0.030	Likely Benign	0.1883	0.3929											-0.91	Neutral	0.001	Benign	0.000	Benign	4.22	Benign	0.00	Affected	4.32	1	0	1	-0.4	14.07
c.237C>G	N79K 2D AIThe SynGAP1 missense variant N79K is listed in gnomAD (ID 6‑33425845‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this conclusion. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375				6-33425845-C-G	1	6.20e-7	-2.811	Likely Benign	0.422	Ambiguous	Likely Benign	0.030	Likely Benign	0.1883	0.3929											-0.91	Neutral	0.001	Benign	0.000	Benign	4.22	Benign	0.00	Affected	4.32	1	0	1	-0.4	14.07
c.3122C>A	P1041H 2D AIThe SynGAP1 missense variant P1041H is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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 yields a benign prediction, and Foldetta’s protein‑folding stability result is unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status because the variant has not been reported there. Thus, based on current predictions, the variant is most likely benign. 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							-5.312	Likely Benign	0.377	Ambiguous	Likely Benign	0.476	Likely Benign	0.1883	0.5434											-3.32	Deleterious	0.999	Probably Damaging	0.917	Probably Damaging	5.45	Benign	0.03	Affected			0	-2	-1.6	40.02
c.1753G>C	A585P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A585P is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools cluster into two groups: the single benign prediction comes from SIFT, while all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic outcome. Based on the convergence of these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000							-10.999	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.549	Likely Pathogenic	0.1884	0.2943		5.44	Destabilizing	0.1	5.92	Destabilizing	5.68	Destabilizing	0.77	Ambiguous	-3.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.33	Pathogenic	0.16	Tolerated			1	-1	-3.4	26.04
c.186T>A	D62E 2D AIThe SynGAP1 missense variant D62E is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.476010	Uncertain	0.575	0.720	0.125							-2.653	Likely Benign	0.095	Likely Benign	Likely Benign	0.065	Likely Benign	0.1884	0.5800											-0.19	Neutral	0.000	Benign	0.000	Benign	4.49	Benign	0.00	Affected			3	2	0.0	14.03
c.186T>G	D62E 2D AIThe SynGAP1 missense variant D62E is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic call comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.476010	Uncertain	0.575	0.720	0.125							-2.653	Likely Benign	0.095	Likely Benign	Likely Benign	0.065	Likely Benign	0.1884	0.5800											-0.19	Neutral	0.000	Benign	0.000	Benign	4.49	Benign	0.00	Affected			3	2	0.0	14.03
c.3238G>C	A1080P 2D AIThe SynGAP1 missense variant A1080P is not 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 a likely benign outcome. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for A1080P, and 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		0.912647	Disordered	0.981457	Binding	0.303	0.900	0.750							-2.429	Likely Benign	0.254	Likely Benign	Likely Benign	0.170	Likely Benign	0.1884	0.5324											-1.15	Neutral	0.996	Probably Damaging	0.833	Possibly Damaging	3.96	Benign	0.02	Affected			1	-1	-3.4	26.04
c.3836C>G	A1279G 2D AIThe SynGAP1 missense variant A1279G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports “Likely Benign.” No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus reports 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 predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.814139	Binding	0.485	0.724	0.750							-3.469	Likely Benign	0.078	Likely Benign	Likely Benign	0.064	Likely Benign	0.1884	0.3473											-0.97	Neutral	0.033	Benign	0.017	Benign	2.69	Benign	0.19	Tolerated			1	0	-2.2	-14.03
c.749T>G	V250G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V250G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default, while only FATHMM predicts a benign outcome. Uncertain results are reported by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is pathogenic. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is consistent with the absence of a ClinVar classification; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.244075	Uncertain	0.778	0.324	0.125							-11.255	Likely Pathogenic	0.917	Likely Pathogenic	Ambiguous	0.900	Likely Pathogenic	0.1884	0.1996		1.65	Ambiguous	0.3	3.18	Destabilizing	2.42	Destabilizing	2.08	Destabilizing	-5.90	Deleterious	0.879	Possibly Damaging	0.997	Probably Damaging	5.75	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.1418T>G	V473G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473G has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the remaining eleven tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) votes pathogenic, and Foldetta also predicts pathogenic. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic based on the collective evidence, and this conclusion does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000							-14.782	Likely Pathogenic	0.936	Likely Pathogenic	Ambiguous	0.683	Likely Pathogenic	0.1885	0.2567		3.45	Destabilizing	0.0	3.40	Destabilizing	3.43	Destabilizing	2.69	Destabilizing	-6.91	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.13	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.3902C>T	P1301L 2D AIThe SynGAP1 missense variant P1301L is reported in gnomAD (ID 6‑33451776‑C‑T) and has no ClinVar entry. All evaluated in silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the unanimous benign predictions and lack of ClinVar pathogenic annotation, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875				6-33451776-C-T	3	1.86e-6	-4.152	Likely Benign	0.099	Likely Benign	Likely Benign	0.072	Likely Benign	0.1886	0.4655											-1.63	Neutral	0.017	Benign	0.028	Benign	2.83	Benign	0.11	Tolerated	3.77	5	-3	-3	5.4	16.04
c.1726T>C	C576R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C576R is listed in ClinVar with an uncertain significance (ClinVar ID 2780076.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it pathogenic, the SGM‑Consensus (derived from the majority of high‑confidence predictors) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. Taken together, the overwhelming majority of computational evidence indicates that C576R is likely pathogenic, a conclusion that is consistent with, but not in conflict with, the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000	Conflicting		2				-14.886	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.579	Likely Pathogenic	0.1887	0.1279		7.20	Destabilizing	1.0	4.09	Destabilizing	5.65	Destabilizing	1.64	Destabilizing	-10.88	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.38	Benign	0.00	Affected	3.37	35	-3	-4	-7.0	53.05
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	0.841	Likely Pathogenic	0.1887	0.6177		0.40	Likely Benign	1.0	0.45	Likely Benign	0.43	Likely Benign	0.80	Ambiguous	-3.37	Deleterious	0.990	Probably Damaging	0.760	Possibly Damaging	5.82	Benign	0.07	Tolerated			0	1	-0.4	-0.94
c.485G>T	R162L 2D AIThe SynGAP1 missense variant R162L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, giving six concordant benign calls. Two tools predict a pathogenic effect: ESM1b and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250							-9.952	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous	0.219	Likely Benign	0.1888	0.5894											-1.83	Neutral	0.001	Benign	0.003	Benign	4.05	Benign	0.15	Tolerated			-3	-2	8.3	-43.03
c.644G>A	G215D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215D is 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—SIFT, PolyPhen‑2 (HumDiv and HumVar), PROVEAN, REVEL, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, and FoldX—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta, which evaluates protein‑folding stability, yields an uncertain result. No other high‑confidence tool contradicts the pathogenic prediction. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000							-9.884	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.807	Likely Pathogenic	0.1888	0.2947		2.23	Destabilizing	0.3	0.91	Ambiguous	1.57	Ambiguous	0.57	Ambiguous	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.71	Benign	0.02	Affected			1	-1	-3.1	58.04
c.2954G>C	S985T 2D AIThe SynGAP1 missense variant S985T is not 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 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 S985T, 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		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750							-5.658	Likely Benign	0.475	Ambiguous	Likely Benign	0.153	Likely Benign	0.1889	0.5844											-1.62	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.54	Benign	0.00	Affected			1	1	0.1	14.03
c.3097T>C	S1033P 2D AIThe SynGAP1 missense variant S1033P is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are not available, so they do not influence the overall assessment. Based on the consensus of all available predictions, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.993473	Binding	0.294	0.737	0.625							-2.046	Likely Benign	0.268	Likely Benign	Likely Benign	0.068	Likely Benign	0.1889	0.5486											0.05	Neutral	0.002	Benign	0.005	Benign	2.68	Benign	0.27	Tolerated			1	-1	-0.8	10.04
c.3173G>A	G1058D 2D AIThe SynGAP1 missense variant G1058D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443725‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.980739	Disordered	0.885724	Binding	0.407	0.929	0.875				6-33443725-G-A	1	6.21e-7	-10.344	Likely Pathogenic	0.391	Ambiguous	Likely Benign	0.177	Likely Benign	0.1889	0.2435											-0.33	Neutral	0.077	Benign	0.042	Benign	5.20	Benign	0.01	Affected	3.77	5	-1	1	-3.1	58.04
c.3937C>A	P1313T 2D AIThe SynGAP1 missense variant P1313T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.970301	Binding	0.452	0.902	0.750							-4.666	Likely Benign	0.071	Likely Benign	Likely Benign	0.149	Likely Benign	0.1889	0.7040											0.03	Neutral	0.000	Benign	0.002	Benign	4.26	Benign	0.14	Tolerated			0	-1	0.9	3.99
c.926G>A	G309D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G309D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are provided by SIFT and Rosetta, whereas the remaining 12 tools (REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus) are pathogenic. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is inconclusive. Taken together, the majority of evidence supports a pathogenic effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.338439	Uncertain	0.882	0.342	0.125							-15.264	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.523	Likely Pathogenic	0.1889	0.2678		2.89	Destabilizing	0.5	-0.03	Likely Benign	1.43	Ambiguous	0.75	Ambiguous	-6.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.88	Pathogenic	0.06	Tolerated			1	-1	-3.1	58.04
c.1547C>A	A516D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A516D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, which scores the substitution as tolerated. In contrast, the majority of algorithms predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence indicates that A516D is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000							-14.621	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.725	Likely Pathogenic	0.1890	0.1679		0.65	Ambiguous	0.2	1.04	Ambiguous	0.85	Ambiguous	0.62	Ambiguous	-5.17	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.23	Pathogenic	0.15	Tolerated			0	-2	-5.3	44.01
c.686A>C	K229T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K229T is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, Foldetta, premPS, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. High‑accuracy methods give a pathogenic result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and a benign outcome from Foldetta. 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	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000							-12.639	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.813	Likely Pathogenic	0.1890	0.3029		0.83	Ambiguous	0.0	-0.08	Likely Benign	0.38	Likely Benign	0.00	Likely Benign	-4.77	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	5.86	Benign	0.01	Affected			0	-1	3.2	-27.07
c.766A>G	N256D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N256D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, Foldetta, premPS, and FATHMM, while the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX is uncertain and therefore not considered evidence for either side. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Taken together, the overall consensus leans toward a pathogenic effect, with 10 tools supporting pathogenicity versus 4 supporting benignity. 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	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250							-12.478	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.701	Likely Pathogenic	0.1890	0.3514		0.69	Ambiguous	0.3	0.21	Likely Benign	0.45	Likely Benign	0.44	Likely Benign	-4.36	Deleterious	0.997	Probably Damaging	0.980	Probably Damaging	5.81	Benign	0.03	Affected			2	1	0.0	0.98
c.1136C>T	S379L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379L is listed in ClinVar as Benign (ClinVar ID 1360860.0) and is present in gnomAD (ID 6‑33438041‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are Rosetta and SIFT. Foldetta and premPS are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence supports a benign impact, which is consistent with the ClinVar classification; there is no contradiction with the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625	Benign		1	6-33438041-C-T	8	4.05e-5	-5.641	Likely Benign	0.173	Likely Benign	Likely Benign	0.469	Likely Benign	0.1891	0.5644		0.39	Likely Benign	0.2	3.38	Destabilizing	1.89	Ambiguous	-0.52	Ambiguous	-0.85	Neutral	0.015	Benign	0.002	Benign	3.83	Benign	0.04	Affected	4.32	11	-3	-2	4.6	26.08	251.9	-48.1	0.6	1.1	0.0	0.5								Uncertain	Ser379 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 leucine are rarely tolerated. Although no negative structural effects are observed in the variant simulations, Leu379 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effect on Gly-rich Ω loop dynamics can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.2324G>C	R775P 2D AIThe SynGAP1 missense variant R775P (ClinVar ID 2959355.0) is classified as Benign in ClinVar and is not reported in gnomAD. 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 and polyPhen‑2 HumVar; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, consistent with the ClinVar designation, and there is no contradiction with the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.895337	Binding	0.320	0.896	0.250	Benign		1				-5.072	Likely Benign	0.452	Ambiguous	Likely Benign	0.168	Likely Benign	0.1891	0.4834											-0.79	Neutral	0.971	Probably Damaging	0.944	Probably Damaging	4.13	Benign	0.07	Tolerated	3.64	6	-2	0	2.9	-59.07
c.302A>G	H101R 2D AIThe SynGAP1 missense variant H101R 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 H101R, 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		0.791621	Disordered	0.688356	Binding	0.370	0.884	0.625							-2.685	Likely Benign	0.211	Likely Benign	Likely Benign	0.141	Likely Benign	0.1891	0.2225											-0.76	Neutral	0.824	Possibly Damaging	0.840	Possibly Damaging	4.21	Benign	0.00	Affected			2	0	-1.3	19.05
c.3406C>A	Q1136K 2D AIThe SynGAP1 missense variant Q1136K is listed in gnomAD (ID 6‑33443958‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: 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 impact, 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		0.903857	Disordered	0.775584	Binding	0.321	0.884	0.875				6-33443958-C-A			-5.698	Likely Benign	0.397	Ambiguous	Likely Benign	0.236	Likely Benign	0.1891	0.4841											-1.43	Neutral	0.625	Possibly Damaging	0.258	Benign	5.55	Benign	0.17	Tolerated	4.32	2	1	1	-0.4	0.04
c.3548A>T	Y1183F 2D AIThe SynGAP1 missense variant Y1183F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no Foldetta data. 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	Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500							-3.527	Likely Benign	0.446	Ambiguous	Likely Benign	0.124	Likely Benign	0.1891	0.2829											-1.42	Neutral	0.951	Possibly Damaging	0.514	Possibly Damaging	2.74	Benign	0.23	Tolerated			7	3	4.1	-16.00
c.481C>A	P161T 2D AIThe SynGAP1 missense variant P161T has no ClinVar entry and is not reported in gnomAD. Computational predictors fall into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375							-8.759	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.153	Likely Benign	0.1891	0.5038											-3.77	Deleterious	0.535	Possibly Damaging	0.310	Benign	3.92	Benign	0.00	Affected			0	-1	0.9	3.99
c.1684C>A	P562T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P562T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign outcome; the only uncertain predictions come from Foldetta and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, while Foldetta remains uncertain. Taken together, the overwhelming majority of computational evidence indicates that P562T is likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022306	Structured	0.023606	Uncertain	0.893	0.200	0.000							-14.747	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.697	Likely Pathogenic	0.1892	0.3454		2.62	Destabilizing	0.1	0.51	Ambiguous	1.57	Ambiguous	0.81	Ambiguous	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.58	Pathogenic	0.00	Affected			0	-1	0.9	3.99
c.235A>G	N79D 2D AIThe SynGAP1 missense variant N79D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375							-3.746	Likely Benign	0.281	Likely Benign	Likely Benign	0.021	Likely Benign	0.1893	0.2535											-0.92	Neutral	0.371	Benign	0.018	Benign	4.19	Benign	0.00	Affected			2	1	0.0	0.98
c.3104C>A	P1035H 2D AIThe SynGAP1 missense variant P1035H is not reported in ClinVar and has no entries in gnomAD. Consensus predictions from multiple in‑silico tools are mixed: benign calls come from SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. No Foldetta stability analysis is available 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		0.945666	Disordered	0.989572	Binding	0.300	0.756	0.625							-5.333	Likely Benign	0.608	Likely Pathogenic	Likely Benign	0.058	Likely Benign	0.1893	0.5669											-0.76	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	2.68	Benign	0.15	Tolerated			0	-2	-1.6	40.02
c.3533A>T	Y1178F 2D AIThe SynGAP1 missense variant Y1178F is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Based on the consensus of all available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.568433	Binding	0.554	0.688	0.250							-3.081	Likely Benign	0.131	Likely Benign	Likely Benign	0.162	Likely Benign	0.1893	0.2758											-0.64	Neutral	0.012	Benign	0.017	Benign	5.44	Benign	0.24	Tolerated			7	3	4.1	-16.00
c.3881C>A	A1294D 2D AIThe SynGAP1 missense variant A1294D is listed in gnomAD (ID 6‑33447929‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment further clarifies the picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenicity. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the lack of a benign ClinVar classification and the presence of the variant in a general population database. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because none exists. 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				6-33447929-C-A			-4.179	Likely Benign	0.369	Ambiguous	Likely Benign	0.224	Likely Benign	0.1893	0.2262											-4.17	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.14	Pathogenic	0.00	Affected	3.77	5	-2	0	-5.3	44.01
c.1728C>G	C576W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, with no contradiction to ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000							-14.796	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.473	Likely Benign	0.1894	0.3017		13.87	Destabilizing	1.5	5.46	Destabilizing	9.67	Destabilizing	0.60	Ambiguous	-10.01	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.38	Benign	0.00	Affected			-8	-2	-3.4	83.07
c.183G>C	E61D 2D AIThe SynGAP1 missense variant E61D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are 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. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.352862	Structured	0.477329	Uncertain	0.518	0.699	0.125							-4.394	Likely Benign	0.231	Likely Benign	Likely Benign	0.035	Likely Benign	0.1895	0.3851											-0.29	Neutral	0.267	Benign	0.585	Possibly Damaging	4.11	Benign	0.00	Affected			3	2	0.0	-14.03
c.183G>T	E61D 2D AIThe SynGAP1 missense variant E61D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are 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. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.352862	Structured	0.477329	Uncertain	0.518	0.699	0.125							-4.394	Likely Benign	0.231	Likely Benign	Likely Benign	0.035	Likely Benign	0.1895	0.3851											-0.29	Neutral	0.267	Benign	0.585	Possibly Damaging	4.11	Benign	0.00	Affected			3	2	0.0	-14.03
c.2332A>G	N778D 2D AIThe SynGAP1 missense variant N778D 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 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		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500							-4.838	Likely Benign	0.446	Ambiguous	Likely Benign	0.093	Likely Benign	0.1896	0.4528											-0.86	Neutral	0.843	Possibly Damaging	0.893	Possibly Damaging	4.21	Benign	0.15	Tolerated			2	1	0.0	0.98
c.3448G>C	A1150P 2D AIThe SynGAP1 missense variant A1150P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (SGM‑Consensus, REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic predictions (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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) is labeled Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for A1150P, 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		0.762850	Disordered	0.795712	Binding	0.371	0.831	0.625							-2.250	Likely Benign	0.180	Likely Benign	Likely Benign	0.152	Likely Benign	0.1896	0.5294											-0.74	Neutral	0.995	Probably Damaging	0.940	Probably Damaging	2.48	Pathogenic	0.25	Tolerated			1	-1	-3.4	26.04
c.1154C>T	S385L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S385L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438059‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus itself is benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of computational evidence indicates the variant is most likely benign, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.733139	Disordered	0.425480	Uncertain	0.341	0.925	0.750	Uncertain		2	6-33438059-C-T	9	4.60e-5	-6.018	Likely Benign	0.167	Likely Benign	Likely Benign	0.304	Likely Benign	0.1897	0.6244		0.16	Likely Benign	0.1	0.08	Likely Benign	0.12	Likely Benign	-0.26	Likely Benign	-0.68	Neutral	0.829	Possibly Damaging	0.706	Possibly Damaging	4.63	Benign	0.01	Affected	4.32	3	-3	-2	4.6	26.08	244.6	-50.1	0.0	0.6	-0.1	0.1								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 leucine are rarely tolerated. Although no negative structural effects are observed in the variant simulations, Leu385 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.
c.2237T>G	V746G 2D AIThe SynGAP1 missense variant V746G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, V746G is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.576597	Binding	0.336	0.867	0.875							-2.971	Likely Benign	0.113	Likely Benign	Likely Benign	0.035	Likely Benign	0.1897	0.2550											-0.89	Neutral	0.136	Benign	0.270	Benign	2.74	Benign	0.02	Affected			-1	-3	-4.6	-42.08
c.2797C>A	H933N 2D AIThe SynGAP1 missense variant H933N is not 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. High‑accuracy predictions show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta are unavailable. Overall, five tools predict pathogenicity versus four predicting benignity, suggesting the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625							-4.333	Likely Benign	0.226	Likely Benign	Likely Benign	0.261	Likely Benign	0.1897	0.3439											-3.65	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.39	Pathogenic	0.04	Affected			2	1	-0.3	-23.04
c.2482A>C	T828P 2D AIThe SynGAP1 missense variant T828P 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, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (2 benign vs. 1 pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is unavailable. Overall, the preponderance of evidence points to a benign impact for T828P, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500							-3.902	Likely Benign	0.466	Ambiguous	Likely Benign	0.280	Likely Benign	0.1898	0.4424											-2.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.12	Tolerated			0	-1	-0.9	-3.99
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	0.1898	0.5214											-4.03	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	2.50	Benign	0.00	Affected	3.77	5	-3	-2	8.3	-43.03
c.3223C>A	Q1075K 2D AIThe SynGAP1 missense variant Q1075K (ClinVar ID 2762879.0) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. 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, is “Likely Benign” because three of the four contributing tools predict benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) 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 “Uncertain” 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	Uncertain		1				-5.135	Likely Benign	0.728	Likely Pathogenic	Likely Benign	0.134	Likely Benign	0.1898	0.4411											-0.67	Neutral	0.963	Probably Damaging	0.959	Probably Damaging	2.75	Benign	1.00	Tolerated	3.77	5	1	1	-0.4	0.04
c.1925A>C	K642T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K642T is listed in ClinVar (ID 437411.0) as Pathogenic and is not reported in gnomAD. Functional prediction tools split in a 7‑to‑5 ratio: pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default, while benign calls come from REVEL, Rosetta, Foldetta, premPS, and FATHMM; FoldX 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 stability outputs) as Benign. Overall, the majority of evidence points to a pathogenic effect, aligning with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000	Likely Pathogenic		1				-12.823	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.484	Likely Benign	0.1899	0.3270		0.53	Ambiguous	0.1	0.30	Likely Benign	0.42	Likely Benign	0.28	Likely Benign	-5.88	Deleterious	0.872	Possibly Damaging	0.839	Possibly Damaging	2.86	Benign	0.00	Affected	3.37	31	0	-1	3.2	-27.07	213.5	-8.7	-0.3	0.4	0.3	0.2				X				Uncertain	The amino side chain of Lys642, located on the surface of an α helix (res. Ser641-Glu666), is not involved in any interactions in the WT simulations. In the variant simulations, the shorter side chain of Thr642 forms hydrogen bonds with Glu643 and Thr640 on the same α helix.Regardless, Lys642 is positioned directly at the GAP-Ras interface, and in the SynGAP-Ras WT simulations, its amino side chain forms salt bridges with the carboxylate groups of Ras residues Asp33 and Asp38. The shorter Thr642 is more likely to prefer hydrogen bonding with Glu643 and Thr640 on the same α helix, even in the Ras complex. Thus, the effect of the residue swap on the complex formation with the GTPase cannot be explored using solvent-only simulations.
c.2179A>G	N727D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N727D has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default, while the SGM‑Consensus score is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward a benign effect, and this does not contradict any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625							-5.640	Likely Benign	0.601	Likely Pathogenic	Likely Benign	0.142	Likely Benign	0.1899	0.4309		0.22	Likely Benign	0.0	0.35	Likely Benign	0.29	Likely Benign	0.36	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.18	Pathogenic	0.08	Tolerated			2	1	0.0	0.98
c.3056G>C	R1019P 2D AIThe SynGAP1 missense variant R1019P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, whereas those that predict pathogenicity 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 conventional tools predict a pathogenic effect, but the most accurate single‑tool prediction is benign and the consensus and folding‑stability analyses are inconclusive. Thus, the variant is most likely pathogenic based on the aggregate 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.			0.856457	Disordered	0.966400	Binding	0.315	0.794	0.500							-3.737	Likely Benign	0.697	Likely Pathogenic	Likely Benign	0.143	Likely Benign	0.1899	0.4521											-2.48	Neutral	0.966	Probably Damaging	0.811	Possibly Damaging	2.38	Pathogenic	0.01	Affected			0	-2	2.9	-59.07
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	0.512	Likely Pathogenic	0.1900	0.3020		0.32	Likely Benign	0.0	0.10	Likely Benign	0.21	Likely Benign	-0.04	Likely Benign	-4.73	Deleterious	0.991	Probably Damaging	0.795	Possibly Damaging	1.94	Pathogenic	0.10	Tolerated			0	-1	3.2	-27.07
c.1172G>A	G391D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G391D is 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, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools, Rosetta and Foldetta, return uncertain results. High‑accuracy methods give a benign call from AlphaMissense‑Optimized; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is also inconclusive. Overall, six tools favor pathogenicity while five favor benignity, with two uncertain. Thus, the variant is most likely pathogenic based on the 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.		C2	0.637480	Disordered	0.409509	Uncertain	0.279	0.741	0.750							-4.651	Likely Benign	0.674	Likely Pathogenic	Likely Benign	0.562	Likely Pathogenic	0.1900	0.1305		2.59	Destabilizing	1.1	1.26	Ambiguous	1.93	Ambiguous	0.22	Likely Benign	-0.95	Neutral	0.999	Probably Damaging	0.960	Probably Damaging	1.32	Pathogenic	0.29	Tolerated			1	-1	-3.1	58.04
c.1616A>C	H539P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H539P missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only FoldX, whereas all other evaluated algorithms—REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000							-15.182	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.913	Likely Pathogenic	0.1900	0.2794		0.22	Likely Benign	0.3	9.08	Destabilizing	4.65	Destabilizing	1.03	Destabilizing	-9.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.29	Pathogenic	0.01	Affected			0	-2	1.6	-40.02
c.1430T>G	M477R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, and FATHMM. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain and is not taken as evidence. Overall, the majority of reliable predictors 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.		GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000							-6.786	Likely Benign	0.552	Ambiguous	Likely Benign	0.442	Likely Benign	0.1901	0.0828		0.48	Likely Benign	0.2	0.77	Ambiguous	0.63	Ambiguous	1.24	Destabilizing	-1.12	Neutral	0.720	Possibly Damaging	0.242	Benign	-1.22	Pathogenic	0.11	Tolerated			0	-1	-6.4	24.99
c.2677C>A	Q893K 2D AIThe SynGAP1 missense variant Q893K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the substitution as benign, and AlphaMissense‑Optimized also predicts a benign outcome. No tool predicts pathogenicity; 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 corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the computational evidence strongly supports a benign classification, and this conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.447267	Uncertain	0.310	0.925	0.750							-5.622	Likely Benign	0.496	Ambiguous	Likely Benign	0.053	Likely Benign	0.1901	0.4381											-1.45	Neutral	0.451	Benign	0.265	Benign	2.78	Benign	0.10	Tolerated			1	1	-0.4	0.04
c.3926T>G	V1309G 2D AIThe SynGAP1 missense variant V1309G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation because the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.712013	Disordered	0.948596	Binding	0.402	0.907	0.750							-2.618	Likely Benign	0.160	Likely Benign	Likely Benign	0.326	Likely Benign	0.1901	0.2144											-3.40	Deleterious	0.391	Benign	0.767	Possibly Damaging	2.40	Pathogenic	0.00	Affected			-1	-3	-4.6	-42.08
c.2320G>C	A774P 2D AIThe SynGAP1 missense variant A774P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.450668	Structured	0.905168	Binding	0.336	0.897	0.250							-3.869	Likely Benign	0.192	Likely Benign	Likely Benign	0.116	Likely Benign	0.1902	0.5749											-0.94	Neutral	0.801	Possibly Damaging	0.481	Possibly Damaging	4.15	Benign	0.18	Tolerated			1	-1	-3.4	26.04
c.2801T>G	M934R 2D AISynGAP1 missense variant M934R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, SIFT, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence leans toward pathogenicity, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625							-1.854	Likely Benign	0.771	Likely Pathogenic	Likely Benign	0.322	Likely Benign	0.1902	0.1243											-3.54	Deleterious	0.969	Probably Damaging	0.624	Possibly Damaging	2.37	Pathogenic	0.11	Tolerated			0	-1	-6.4	24.99
c.838T>A	Y280N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only SIFT, whereas all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming consensus of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for Y280N. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125							-13.090	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.589	Likely Pathogenic	0.1902	0.0212		4.26	Destabilizing	0.2	4.18	Destabilizing	4.22	Destabilizing	1.82	Destabilizing	-8.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.95	Pathogenic	0.06	Tolerated			-2	-2	-2.2	-49.07
c.1886T>G	V629G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V629G missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining eleven tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) uniformly predict a pathogenic outcome; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Taken together, the overwhelming majority of evidence indicates that V629G is likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.040537	Structured	0.034796	Uncertain	0.970	0.236	0.000							-13.150	Likely Pathogenic	0.871	Likely Pathogenic	Ambiguous	0.678	Likely Pathogenic	0.1903	0.2240		3.81	Destabilizing	0.0	4.52	Destabilizing	4.17	Destabilizing	1.94	Destabilizing	-6.47	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.07	Benign	0.00	Affected			-1	-3	-4.6	-42.08
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	0.1903	0.4304											-1.33	Neutral	0.989	Probably Damaging	0.859	Possibly Damaging	4.08	Benign	0.00	Affected			0	-2	2.9	-59.07
c.140G>T	R47L 2D AIThe SynGAP1 missense variant R47L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R47L. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125							-5.758	Likely Benign	0.664	Likely Pathogenic	Likely Benign	0.130	Likely Benign	0.1904	0.5206											-1.76	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	4.04	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.2828G>A	G943D 2D AIThe SynGAP1 missense variant G943D is not reported in ClinVar and is absent from gnomAD. In silico predictors that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Taken together, the overwhelming majority of predictions indicate a benign effect, and this conclusion does not contradict any ClinVar status (none is assigned). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.973328	Disordered	0.860437	Binding	0.372	0.910	0.750							-7.951	In-Between	0.304	Likely Benign	Likely Benign	0.296	Likely Benign	0.1904	0.2826											-0.28	Neutral	0.224	Benign	0.113	Benign	2.85	Benign	0.11	Tolerated			1	-1	-3.1	58.04
c.3205C>A	Q1069K 2D AIThe SynGAP1 missense variant Q1069K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of computational evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.981477	Binding	0.333	0.906	0.875							-5.080	Likely Benign	0.542	Ambiguous	Likely Benign	0.099	Likely Benign	0.1904	0.5071											-0.88	Neutral	0.625	Possibly Damaging	0.266	Benign	2.77	Benign	0.28	Tolerated			1	1	-0.4	0.04
c.1278C>A	N426K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426K resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000							-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.197	Likely Benign	0.1906	0.2822		0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			1	0	-0.4	14.07
c.1278C>G	N426K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426K is located in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, while those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect on protein stability. Overall, the majority of predictions lean toward pathogenicity, with a split in the most reliable methods. Therefore, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000							-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.197	Likely Benign	0.1906	0.2822		0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			1	0	-0.4	14.07
c.3888G>C	E1296D 2D AIThe SynGAP1 missense variant E1296D 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		0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625							-3.566	Likely Benign	0.276	Likely Benign	Likely Benign	0.299	Likely Benign	0.1906	0.3443											-2.15	Neutral	0.980	Probably Damaging	0.812	Possibly Damaging	2.59	Benign	0.04	Affected			3	2	0.0	-14.03
c.3888G>T	E1296D 2D AIThe SynGAP1 missense variant E1296D 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		0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625							-3.566	Likely Benign	0.276	Likely Benign	Likely Benign	0.493	Likely Benign	0.1906	0.3443											-2.15	Neutral	0.980	Probably Damaging	0.812	Possibly Damaging	2.59	Benign	0.04	Affected			3	2	0.0	-14.03
c.880A>C	T294P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T294P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX (Uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool reports a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is pathogenic; SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.316932	Uncertain	0.919	0.267	0.125							-17.477	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.741	Likely Pathogenic	0.1906	0.4479		1.97	Ambiguous	0.3	5.18	Destabilizing	3.58	Destabilizing	1.15	Destabilizing	-5.52	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-0.19	Pathogenic	0.01	Affected			0	-1	-0.9	-3.99
c.8G>T	R3M 2D AIThe SynGAP1 missense variant R3M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” and Foldetta data are unavailable. Overall, the majority of evidence supports a benign classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.550331	Binding	0.358	0.920	0.875							-4.655	Likely Benign	0.618	Likely Pathogenic	Likely Benign	0.097	Likely Benign	0.1906	0.4795											0.00	Neutral	0.872	Possibly Damaging	0.162	Benign	3.96	Benign	0.00	Affected			0	-1	6.4	-24.99
c.284A>G	H95R 2D AIThe SynGAP1 missense variant H95R is reported in gnomAD (variant ID 6‑33425892‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates 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 results are not available. Overall, the preponderance of evidence indicates that H95R is most likely benign, and this conclusion 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		0.661982	Disordered	0.590542	Binding	0.335	0.875	0.625				6-33425892-A-G	1	6.20e-7	-2.789	Likely Benign	0.153	Likely Benign	Likely Benign	0.043	Likely Benign	0.1907	0.2087											-1.31	Neutral	0.084	Benign	0.009	Benign	4.20	Benign	0.00	Affected	4.32	1	0	2	-1.3	19.05
c.901G>C	A301P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301P 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 polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the preponderance of 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	C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375							-3.808	Likely Benign	0.085	Likely Benign	Likely Benign	0.225	Likely Benign	0.1907	0.5371		-0.47	Likely Benign	0.1	-0.41	Likely Benign	-0.44	Likely Benign	0.40	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.11	Benign	0.06	Tolerated			1	-1	-3.4	26.04
c.810G>C	E270D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E270D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. The majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Rosetta. Tools with inconclusive results—FoldX, Foldetta, and premPS—are listed as uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125							-11.954	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.379	Likely Benign	0.1908	0.2540		1.52	Ambiguous	0.1	2.15	Destabilizing	1.84	Ambiguous	0.91	Ambiguous	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.60	Pathogenic	0.02	Affected			3	2	0.0	-14.03
c.810G>T	E270D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E270D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. The majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, Rosetta, and the SGM‑Consensus (which is “Likely Pathogenic”). Predictions that are inconclusive or uncertain are FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus also indicating a likely pathogenic outcome, while Foldetta’s stability analysis is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E270D, and this conclusion is consistent with the lack of ClinVar annotation (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125							-11.954	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.383	Likely Benign	0.1908	0.2540		1.52	Ambiguous	0.1	2.15	Destabilizing	1.84	Ambiguous	0.91	Ambiguous	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.60	Pathogenic	0.02	Affected			3	2	0.0	-14.03
c.1841A>T	Y614F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or unavailable results come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is unavailable. Overall, the majority of reliable predictors indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000							-5.584	Likely Benign	0.630	Likely Pathogenic	Likely Benign	0.364	Likely Benign	0.1909	0.2762		0.09	Likely Benign	0.2	0.98	Ambiguous	0.54	Ambiguous	0.78	Ambiguous	-3.75	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.42	Benign	0.07	Tolerated			7	3	4.1	-16.00
c.2742C>A	D914E 2D AIThe SynGAP1 missense variant D914E is reported in gnomAD (ID 6‑33443294‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. 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, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250				6-33443294-C-A	5	3.10e-6	-3.231	Likely Benign	0.170	Likely Benign	Likely Benign	0.133	Likely Benign	0.1909	0.7088											-0.29	Neutral	0.893	Possibly Damaging	0.418	Benign	2.87	Benign	1.00	Tolerated	3.77	5	2	3	0.0	14.03
c.2742C>G	D914E 2D AIThe SynGAP1 missense variant D914E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification for D914E, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250							-3.231	Likely Benign	0.170	Likely Benign	Likely Benign	0.133	Likely Benign	0.1909	0.7088											-0.29	Neutral	0.893	Possibly Damaging	0.418	Benign	2.87	Benign	1.00	Tolerated	3.77	5	2	3	0.0	14.03
c.3254G>T	R1085L 2D AIThe SynGAP1 missense variant R1085L is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R1085L, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000							-3.674	Likely Benign	0.734	Likely Pathogenic	Likely Benign	0.243	Likely Benign	0.1909	0.4568											-2.38	Neutral	0.997	Probably Damaging	0.993	Probably Damaging	2.72	Benign	0.01	Affected			-3	-2	8.3	-43.03
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	0.638	Likely Pathogenic	0.1909	0.4660		0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			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	0.638	Likely Pathogenic	0.1909	0.4660		0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			3	0	0.3	9.01
c.218G>T	R73M 2D AIThe SynGAP1 R73M missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus methods give a benign signal: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this 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		0.501700	Disordered	0.453164	Uncertain	0.332	0.826	0.375							-5.343	Likely Benign	0.495	Ambiguous	Likely Benign	0.135	Likely Benign	0.1910	0.4238											-1.10	Neutral	0.872	Possibly Damaging	0.113	Benign	4.00	Benign	0.00	Affected			0	-1	6.4	-24.99
c.2968T>C	S990P 2D AIThe SynGAP1 missense variant S990P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of any ClinVar pathogenic annotation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.902387	Binding	0.301	0.919	0.750							-3.150	Likely Benign	0.122	Likely Benign	Likely Benign	0.117	Likely Benign	0.1910	0.5345											-1.95	Neutral	0.586	Possibly Damaging	0.377	Benign	2.74	Benign	0.01	Affected			1	-1	-0.8	10.04
c.3511G>C	A1171P 2D AIThe SynGAP1 A1171P missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. High‑accuracy tools therefore provide a benign consensus (SGM‑Consensus) with no definitive pathogenic signal, and no evidence from Foldetta. Based on the aggregate 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	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500							-3.625	Likely Benign	0.897	Likely Pathogenic	Ambiguous	0.355	Likely Benign	0.1910	0.3810											-1.00	Neutral	0.918	Possibly Damaging	0.601	Possibly Damaging	5.31	Benign	0.05	Affected			1	-1	-3.4	26.04
c.1681T>C	F561L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only SIFT, whereas the remaining evaluated algorithms (REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic or likely pathogenic outcome; FoldX is listed as uncertain and is therefore not considered evidence for either side. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for F561L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000							-8.947	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.656	Likely Pathogenic	0.1911	0.2629		1.72	Ambiguous	0.2	2.52	Destabilizing	2.12	Destabilizing	1.39	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-0.81	Pathogenic	0.32	Tolerated			2	0	1.0	-34.02
c.1683C>A	F561L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the remaining tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000							-8.947	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.492	Likely Benign	0.1911	0.2629		1.72	Ambiguous	0.2	2.52	Destabilizing	2.12	Destabilizing	1.39	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-0.81	Pathogenic	0.32	Tolerated			2	0	1.0	-34.02
c.1683C>G	F561L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the remaining tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000							-8.947	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.493	Likely Benign	0.1911	0.2629		1.72	Ambiguous	0.2	2.52	Destabilizing	2.12	Destabilizing	1.39	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-0.81	Pathogenic	0.32	Tolerated			2	0	1.0	-34.02
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	0.1911	0.8236											-1.59	Neutral	0.994	Probably Damaging	0.891	Possibly Damaging	2.18	Pathogenic	0.05	Affected			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	0.1911	0.8236											-1.59	Neutral	0.994	Probably Damaging	0.891	Possibly Damaging	2.18	Pathogenic	0.05	Affected			3	2	0.0	14.03
c.2234C>A	P745H 2D AIThe SynGAP1 missense variant P745H 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, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. 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 (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 majority of computational 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		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875							-5.569	Likely Benign	0.120	Likely Benign	Likely Benign	0.200	Likely Benign	0.1912	0.3403											-2.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.53	Benign	0.00	Affected			0	-2	-1.6	40.02
c.3167G>A	G1056D 2D AIThe SynGAP1 missense variant G1056D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (six benign vs. three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.988291	Disordered	0.868632	Binding	0.402	0.935	0.875							-10.352	Likely Pathogenic	0.328	Likely Benign	Likely Benign	0.380	Likely Benign	0.1912	0.2626											0.09	Neutral	0.666	Possibly Damaging	0.193	Benign	1.83	Pathogenic	0.92	Tolerated			1	-1	-3.1	58.04
c.367G>A	A123T 2D AIThe SynGAP1 missense variant A123T is reported as “Likely Benign” in ClinVar and is not present in gnomAD. Prediction tools that assess functional impact all converge on a benign outcome: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.689505	Binding	0.324	0.886	0.750							-3.999	Likely Benign	0.077	Likely Benign	Likely Benign	0.117	Likely Benign	0.1912	0.7109											0.59	Neutral	0.004	Benign	0.001	Benign	4.29	Benign	0.52	Tolerated			1	0	-2.5	30.03
c.40C>A	P14T 2D AIThe SynGAP1 missense variant P14T is reported in gnomAD (ID 6‑33420304‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also reports likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for P14T, 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		0.433034	Structured	0.471596	Uncertain	0.399	0.909	0.375				6-33420304-C-A			-3.261	Likely Benign	0.150	Likely Benign	Likely Benign	0.078	Likely Benign	0.1912	0.6658											-0.27	Neutral	0.212	Benign	0.014	Benign	4.20	Benign	0.00	Affected	4.32	1	-1	0	0.9	3.99
c.3458G>T	R1153L 2D AIThe SynGAP1 missense variant R1153L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When predictions are grouped by consensus, the majority of algorithms (seven of nine) favor a deleterious effect, while only two suggest a benign outcome. High‑accuracy assessments further support a damaging interpretation: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta results are not available. Overall, the evidence points to a pathogenic impact for R1153L, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625							-3.595	Likely Benign	0.985	Likely Pathogenic	Likely Pathogenic	0.470	Likely Benign	0.1913	0.4400											-5.05	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.48	Pathogenic	0.00	Affected			-3	-2	8.3	-43.03
c.3617A>C	K1206T 2D AIThe SynGAP1 missense variant K1206T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206T. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375							-10.161	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.290	Likely Benign	0.1913	0.3354											-3.92	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.40	Pathogenic	0.01	Affected			0	-1	3.2	-27.07
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	0.1914	0.4675											-2.26	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	3.89	Benign	0.00	Affected			0	-2	-1.6	40.02
c.2023A>G	N675D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675D is not 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, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments give AlphaMissense‑Optimized a benign call, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) a pathogenic call, and Foldetta an uncertain result. With an equal split of general predictions but a pathogenic majority in the high‑accuracy consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000							-12.829	Likely Pathogenic	0.497	Ambiguous	Likely Benign	0.246	Likely Benign	0.1914	0.4901		1.41	Ambiguous	0.4	-0.26	Likely Benign	0.58	Ambiguous	1.05	Destabilizing	-3.87	Deleterious	0.997	Probably Damaging	0.865	Possibly Damaging	3.53	Benign	0.17	Tolerated			2	1	0.0	0.98
c.194A>C	H65P 2D AIThe SynGAP1 missense variant H65P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for H65P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.476188	Uncertain	0.458	0.758	0.125							-1.732	Likely Benign	0.479	Ambiguous	Likely Benign	0.103	Likely Benign	0.1915	0.3701											-1.47	Neutral	0.676	Possibly Damaging	0.227	Benign	4.16	Benign	0.00	Affected			0	-2	1.6	-40.02
c.2195G>C	R732T 2D AISynGAP1 missense variant R732T is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b). AlphaMissense‑Default remains uncertain. The high‑accuracy AlphaMissense‑Optimized predicts a benign effect, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors a benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact, which does not contradict the current ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.846163	Disordered	0.412403	Uncertain	0.427	0.673	0.750	Uncertain		1				-8.545	Likely Pathogenic	0.434	Ambiguous	Likely Benign	0.075	Likely Benign	0.1915	0.3153											-1.96	Neutral	0.999	Probably Damaging	0.892	Possibly Damaging	2.59	Benign	0.12	Tolerated	3.59	7	-1	-1	3.8	-55.08
c.2710A>C	M904L 2D AIThe SynGAP1 missense variant M904L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.589073	Binding	0.350	0.920	0.250							-1.839	Likely Benign	0.074	Likely Benign	Likely Benign	0.050	Likely Benign	0.1915	0.4584											-0.24	Neutral	0.000	Benign	0.001	Benign	2.86	Benign	0.17	Tolerated			4	2	1.9	-18.03
c.2710A>T	M904L 2D AIThe SynGAP1 missense variant M904L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.589073	Binding	0.350	0.920	0.250							-1.839	Likely Benign	0.074	Likely Benign	Likely Benign	0.050	Likely Benign	0.1915	0.4584											-0.24	Neutral	0.000	Benign	0.001	Benign	2.86	Benign	0.17	Tolerated			4	2	1.9	-18.03
c.548A>G	H183R 2D AIThe SynGAP1 H183R missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus (majority vote) also pathogenic; Foldetta stability analysis is unavailable. Based on the majority of computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500							-10.937	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.368	Likely Benign	0.1915	0.2249											-5.43	Deleterious	0.596	Possibly Damaging	0.142	Benign	3.90	Benign	0.13	Tolerated			2	0	-1.3	19.05
c.538T>C	S180P 2D AIThe SynGAP1 missense variant S180P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500							-14.574	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.225	Likely Benign	0.1916	0.4735											-3.19	Deleterious	0.917	Possibly Damaging	0.446	Benign	3.81	Benign	0.01	Affected			1	-1	-0.8	10.04
c.2035T>C	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and FATHMM, while the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (FoldX and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for F679L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000							-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.506	Likely Pathogenic	0.1918	0.3493		1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			2	0	1.0	-34.02
c.2037T>A	F679L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F679L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, FATHMM, and Foldetta, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. The majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000							-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.287	Likely Benign	0.1918	0.3493		1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			2	0	1.0	-34.02
c.2037T>G	F679L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and premPS are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000							-11.395	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.287	Likely Benign	0.1918	0.3493		1.07	Ambiguous	0.0	-0.36	Likely Benign	0.36	Likely Benign	0.82	Ambiguous	-5.91	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	3.54	Benign	0.03	Affected			2	0	1.0	-34.02
c.3480C>A	N1160K 2D AIThe SynGAP1 missense variant N1160K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375							-3.768	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic	0.188	Likely Benign	0.1919	0.5017											-3.92	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.04	Affected			1	0	-0.4	14.07
c.3480C>G	N1160K 2D AIThe SynGAP1 missense variant N1160K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375							-3.768	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic	0.189	Likely Benign	0.1919	0.5017											-3.92	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.04	Affected			1	0	-0.4	14.07
c.1933T>A	F645I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F645I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are given by premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) report uncertain or inconclusive outcomes. High‑accuracy assessments indicate that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the majority of evaluated predictors (five pathogenic vs four benign) lean toward a pathogenic effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no entry for F645I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000							-13.055	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	0.299	Likely Benign	0.1920	0.2891		1.12	Ambiguous	0.2	1.68	Ambiguous	1.40	Ambiguous	1.01	Destabilizing	-4.24	Deleterious	0.190	Benign	0.019	Benign	3.44	Benign	0.04	Affected			1	0	1.7	-34.02
c.2455G>C	A819P 2D AIThe SynGAP1 missense variant A819P is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact for A819P, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625							-5.542	Likely Benign	0.789	Likely Pathogenic	Ambiguous	0.342	Likely Benign	0.1920	0.5753											-3.18	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	2.17	Pathogenic	0.01	Affected			1	-1	-3.4	26.04
c.3350G>A	G1117D 2D AIThe SynGAP1 missense variant G1117D is catalogued in gnomAD (6‑33443902‑G‑A) but has no ClinVar entry. In silico predictors that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic effect, while ESM1b and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar classification (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750				6-33443902-G-A	1	6.61e-7	-7.594	In-Between	0.358	Ambiguous	Likely Benign	0.315	Likely Benign	0.1920	0.2635											-0.38	Neutral	0.666	Possibly Damaging	0.355	Benign	4.57	Benign	0.24	Tolerated	4.32	2	-1	1	-3.1	58.04
c.1880C>G	A627G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A627G is not 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 comprise SGM‑Consensus, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.037862	Uncertain	0.970	0.210	0.000							-11.716	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign	0.458	Likely Benign	0.1921	0.2990		1.38	Ambiguous	0.1	2.07	Destabilizing	1.73	Ambiguous	1.25	Destabilizing	-3.96	Deleterious	0.997	Probably Damaging	0.876	Possibly Damaging	2.51	Benign	0.01	Affected			1	0	-2.2	-14.03
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	0.618	Likely Pathogenic	0.1923	0.1624		5.56	Destabilizing	7.3	3.08	Destabilizing	4.32	Destabilizing	0.42	Likely Benign	-0.67	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	3	-1	1	-3.1	58.04
c.2992G>C	A998P 2D AIThe SynGAP1 missense variant A998P is not 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, including the high‑accuracy tools, points to a benign effect for A998P. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.759478	Disordered	0.951758	Binding	0.318	0.902	0.500							-2.220	Likely Benign	0.071	Likely Benign	Likely Benign	0.171	Likely Benign	0.1924	0.5106											-0.40	Neutral	0.971	Probably Damaging	0.690	Possibly Damaging	4.31	Benign	0.00	Affected			1	-1	-3.4	26.04
c.3299G>A	G1100D 2D AIThe SynGAP1 missense variant G1100D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875							-5.235	Likely Benign	0.577	Likely Pathogenic	Likely Benign	0.141	Likely Benign	0.1924	0.3043											-1.67	Neutral	0.049	Benign	0.030	Benign	1.93	Pathogenic	0.01	Affected			1	-1	-3.1	58.04
c.3353G>A	S1118N 2D AIThe SynGAP1 missense variant S1118N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that the variant is most likely benign, and this assessment is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750							-6.551	Likely Benign	0.102	Likely Benign	Likely Benign	0.223	Likely Benign	0.1924	0.4215											-0.53	Neutral	0.901	Possibly Damaging	0.433	Benign	5.26	Benign	0.06	Tolerated			1	1	-2.7	27.03
c.1493T>C	M498T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M498T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: all but one (polyPhen‑2 HumVar) predict pathogenicity, while polyPhen‑2 HumVar alone predicts benign. Uncertain predictions (ESM1b and AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy methods reinforce the pathogenic view: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains inconclusive. Overall, the preponderance of evidence indicates that M498T is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.399612	Uncertain	0.932	0.158	0.000							-7.477	In-Between	0.869	Likely Pathogenic	Ambiguous	0.672	Likely Pathogenic	0.1925	0.1630		2.46	Destabilizing	0.1	2.62	Destabilizing	2.54	Destabilizing	1.41	Destabilizing	-3.80	Deleterious	0.803	Possibly Damaging	0.343	Benign	-1.19	Pathogenic	0.02	Affected			-1	-1	-2.6	-30.09
c.1597G>C	A533P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict benign. Only FATHMM predicts pathogenic. Stability‑based methods are inconclusive: FoldX, Rosetta, and the combined Foldetta output are listed as uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as unavailable. Overall, the consensus of the majority of tools indicates a benign impact. This prediction 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 Benign	GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000							-3.951	Likely Benign	0.081	Likely Benign	Likely Benign	0.187	Likely Benign	0.1925	0.5299		-0.93	Ambiguous	0.3	-0.92	Ambiguous	-0.93	Ambiguous	-0.18	Likely Benign	-0.48	Neutral	0.000	Benign	0.001	Benign	-1.26	Pathogenic	0.09	Tolerated			1	-1	-3.4	26.04
c.2423T>G	V808G 2D AIThe SynGAP1 V808G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of individual predictors (five benign vs. three pathogenic) support a benign classification, and this is not contradicted by any ClinVar annotation. Thus, based on the available predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500							-6.635	Likely Benign	0.460	Ambiguous	Likely Benign	0.268	Likely Benign	0.1925	0.3336											-2.94	Deleterious	0.069	Benign	0.135	Benign	2.27	Pathogenic	0.00	Affected			-1	-3	-4.6	-42.08
c.3439A>C	T1147P 2D AIThe SynGAP1 missense variant T1147P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.746520	Binding	0.345	0.839	0.875							-2.849	Likely Benign	0.072	Likely Benign	Likely Benign	0.425	Likely Benign	0.1925	0.4490											-2.17	Neutral	0.000	Benign	0.002	Benign	5.41	Benign	0.02	Affected			0	-1	-0.9	-3.99
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	0.197	Likely Benign	0.1926	0.3092		0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	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	0.197	Likely Benign	0.1926	0.3092		0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	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.3277C>A	Q1093K 2D AIThe SynGAP1 missense variant Q1093K is reported in gnomAD (variant ID 6‑33443829‑C‑A) but has no ClinVar entry. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts benign. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that 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		0.919029	Disordered	0.983312	Binding	0.351	0.886	1.000				6-33443829-C-A			-3.919	Likely Benign	0.558	Ambiguous	Likely Benign	0.061	Likely Benign	0.1926	0.5861											-0.92	Neutral	0.224	Benign	0.091	Benign	2.78	Benign	0.06	Tolerated	3.77	5	1	1	-0.4	0.04
c.3607C>G	H1203D 2D AIThe SynGAP1 missense variant H1203D is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.618285	Disordered	0.527023	Binding	0.892	0.589	0.250	Uncertain		2				-6.729	Likely Benign	0.525	Ambiguous	Likely Benign	0.403	Likely Benign	0.1926	0.0530											-1.89	Neutral	0.473	Possibly Damaging	0.265	Benign	5.51	Benign	0.24	Tolerated	3.77	5	1	-1	-0.3	-22.05
c.1552T>C	Y518H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y518H, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000	Uncertain		1				-9.797	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.496	Likely Benign	0.1927	0.0212		2.39	Destabilizing	0.4	0.82	Ambiguous	1.61	Ambiguous	1.31	Destabilizing	-4.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.08	Tolerated			0	2	-1.9	-26.03
c.2846G>A	G949D 2D AIThe SynGAP1 missense variant G949D is not 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, polyPhen‑2 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. Overall, the majority of high‑confidence predictors (5 pathogenic vs. 4 benign) indicate a pathogenic impact. 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.			0.988861	Disordered	0.874971	Binding	0.365	0.923	0.750							-8.692	Likely Pathogenic	0.239	Likely Benign	Likely Benign	0.316	Likely Benign	0.1927	0.2826											0.25	Neutral	0.945	Possibly Damaging	0.753	Possibly Damaging	2.21	Pathogenic	0.02	Affected			1	-1	-3.1	58.04
c.3006T>A	H1002Q 2D AIThe SynGAP1 missense variant H1002Q is 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		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500							-5.071	Likely Benign	0.650	Likely Pathogenic	Likely Benign	0.140	Likely Benign	0.1927	0.3510											-1.83	Neutral	0.801	Possibly Damaging	0.602	Possibly Damaging	2.77	Benign	0.23	Tolerated			3	0	-0.3	-9.01
c.3006T>G	H1002Q 2D AIThe SynGAP1 missense variant H1002Q is 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 conclusion, so the variant is most likely benign. 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							-5.071	Likely Benign	0.650	Likely Pathogenic	Likely Benign	0.140	Likely Benign	0.1927	0.3510											-1.83	Neutral	0.801	Possibly Damaging	0.602	Possibly Damaging	2.77	Benign	0.23	Tolerated			3	0	-0.3	-9.01
c.2855G>A	G952D 2D AIThe SynGAP1 missense variant G952D is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools overwhelmingly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Benign. Only SIFT predicts a pathogenic outcome, and ESM1b remains uncertain. High‑accuracy assessments corroborate the benign trend: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the computational evidence strongly supports a benign classification, 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		0.985964	Disordered	0.910621	Binding	0.341	0.926	0.750							-7.299	In-Between	0.274	Likely Benign	Likely Benign	0.241	Likely Benign	0.1928	0.2826											-0.75	Neutral	0.033	Benign	0.015	Benign	3.20	Benign	0.05	Affected			1	-1	-3.1	58.04
c.1993T>A	Y665N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y665N variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of conventional predictors lean toward a benign impact, and this assessment does not contradict ClinVar status (none). Thus, the variant is most likely benign based on the prevailing predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000							-11.189	Likely Pathogenic	0.470	Ambiguous	Likely Benign	0.219	Likely Benign	0.1929	0.0573		1.11	Ambiguous	0.1	1.43	Ambiguous	1.27	Ambiguous	0.50	Likely Benign	-3.03	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.88	Tolerated			-2	-2	-2.2	-49.07
c.3125A>G	Q1042R 2D AIThe SynGAP1 missense variant Q1042R is listed in ClinVar (ID 2662705.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443677‑A‑G). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the majority of evidence supports a benign impact for Q1042R, and this conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.959333	Binding	0.310	0.846	0.625	Uncertain		2	6-33443677-A-G	2	1.24e-6	-2.928	Likely Benign	0.413	Ambiguous	Likely Benign	0.300	Likely Benign	0.1929	0.3887											-1.39	Neutral	0.586	Possibly Damaging	0.120	Benign	5.48	Benign	0.12	Tolerated	3.77	5	1	1	-1.0	28.06
c.976C>A	H326N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326N has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and SIFT, whereas a majority (seven) predict a pathogenic outcome: SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the balance of evidence points to a pathogenic impact for H326N, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000							-8.914	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.409	Likely Benign	0.1929	0.2552		0.81	Ambiguous	0.2	1.48	Ambiguous	1.15	Ambiguous	0.97	Ambiguous	-5.63	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.95	Pathogenic	0.11	Tolerated			2	1	-0.3	-23.04
c.2701G>C	A901P 2D AIThe SynGAP1 missense variant A901P 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, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is not available. Overall, the majority of evidence supports a benign interpretation, and there is no conflict with ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.489838	Uncertain	0.306	0.917	0.375							-4.035	Likely Benign	0.175	Likely Benign	Likely Benign	0.124	Likely Benign	0.1930	0.5941											-0.17	Neutral	0.918	Possibly Damaging	0.500	Possibly Damaging	2.65	Benign	0.19	Tolerated			1	-1	-3.4	26.04
c.2915C>A	P972H 2D AIThe SynGAP1 missense variant P972H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign classification, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.954150	Binding	0.472	0.904	0.625							-4.791	Likely Benign	0.087	Likely Benign	Likely Benign	0.049	Likely Benign	0.1930	0.4798											-1.62	Neutral	0.589	Possibly Damaging	0.229	Benign	4.19	Benign	0.02	Affected			0	-2	-1.6	40.02
c.2185A>G	N729D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729D is predicted to be benign by all available in‑silico tools. Consensus predictors (REVEL, SIFT, polyPhen‑2 HumDiv/HumVar, PROVEAN, premPS, FoldX, Rosetta, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly report a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign impact on protein stability. ClinVar contains no entry for this variant, and it is not listed in gnomAD. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625							-5.117	Likely Benign	0.270	Likely Benign	Likely Benign	0.054	Likely Benign	0.1931	0.2250		0.03	Likely Benign	0.2	0.10	Likely Benign	0.07	Likely Benign	0.14	Likely Benign	-1.22	Neutral	0.390	Benign	0.144	Benign	3.41	Benign	0.55	Tolerated			2	1	0.0	0.98
c.932A>G	H311R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H311R is 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, SIFT, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. Tools with uncertain or inconclusive results are Rosetta, Foldetta, and premPS. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized indicates benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenic, and Foldetta remains uncertain. Overall, the balance of evidence favors a pathogenic 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 Pathogenic	C2	0.229226	Structured	0.354792	Uncertain	0.902	0.314	0.125							-9.825	Likely Pathogenic	0.719	Likely Pathogenic	Likely Benign	0.532	Likely Pathogenic	0.1931	0.2490		0.43	Likely Benign	0.1	0.85	Ambiguous	0.64	Ambiguous	0.70	Ambiguous	-5.72	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.94	Pathogenic	0.14	Tolerated			2	0	-1.3	19.05
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	0.1933	0.4069											-1.78	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.04	Pathogenic	0.00	Affected	4.32	1	1	1	-2.7	27.03
c.1268A>T	Y423F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423F is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess sequence conservation and functional impact uniformly classify the substitution as benign: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic effect, while premPS is inconclusive. High‑accuracy methods give consistent benign results: AlphaMissense‑Optimized is benign, the SGM‑Consensus is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the overwhelming majority of evidence supports a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000							-5.533	Likely Benign	0.181	Likely Benign	Likely Benign	0.149	Likely Benign	0.1934	0.2337		0.03	Likely Benign	0.1	-0.05	Likely Benign	-0.01	Likely Benign	0.76	Ambiguous	-2.30	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	3.45	Benign	0.60	Tolerated			7	3	4.1	-16.00
c.3560T>G	M1187R 2D AIThe SynGAP1 missense variant M1187R is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as benign, and Foldetta results are unavailable. Overall, the majority of individual predictors (seven) indicate pathogenicity, whereas only three suggest benignity. Consequently, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.562014	Disordered	0.499801	Uncertain	0.597	0.636	0.625							-3.350	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic	0.557	Likely Pathogenic	0.1934	0.1000											-0.73	Neutral	0.968	Probably Damaging	0.978	Probably Damaging	5.52	Benign	0.02	Affected			0	-1	-6.4	24.99
c.436T>C	S146P 2D AIThe SynGAP1 missense variant S146P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for S146P, 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		0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625							-13.292	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.215	Likely Benign	0.1934	0.4627											-3.11	Deleterious	0.392	Benign	0.230	Benign	3.60	Benign	0.00	Affected			1	-1	-0.8	10.04
c.776G>T	R259L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R259L is not reported in ClinVar and is absent from gnomAD. Among the available in‑silico predictors, the benign‑predicted tools are Rosetta and FATHMM, while the pathogenic‑predicted tools include SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Foldetta and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of predictions support a pathogenic effect, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.338208	Uncertain	0.885	0.255	0.250							-14.185	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.894	Likely Pathogenic	0.1934	0.5499		2.84	Destabilizing	1.1	0.16	Likely Benign	1.50	Ambiguous	0.64	Ambiguous	-6.43	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	5.87	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.855C>G	C285W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C285W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and Rosetta, whereas pathogenic predictions are made by SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy subset confirms this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity, and Foldetta remains uncertain. No prediction tool is missing or inconclusive enough to alter the overall assessment. Consequently, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000							-9.017	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.327	Likely Benign	0.1934	0.3697		3.35	Destabilizing	1.1	-2.28	Stabilizing	0.54	Ambiguous	0.61	Ambiguous	-8.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.11	Tolerated			-8	-2	-3.4	83.07
c.2048T>G	I683S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. No prediction or folding stability result is missing or inconclusive; all available evidence points to a deleterious effect. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000							-11.443	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.552	Likely Pathogenic	0.1936	0.1320		2.53	Destabilizing	0.2	1.94	Ambiguous	2.24	Destabilizing	1.35	Destabilizing	-5.88	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.29	Benign	0.05	Affected			-1	-2	-5.3	-26.08
c.757A>C	N253H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N253H is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include FoldX, FATHMM, and premPS, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta provide inconclusive results and are treated as unavailable. No contradictory evidence is present in ClinVar. Overall, the preponderance of evidence from multiple in‑silico predictors points to a pathogenic effect for the variant, and this conclusion does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250							-12.199	Likely Pathogenic	0.899	Likely Pathogenic	Ambiguous	0.832	Likely Pathogenic	0.1936	0.8033		0.31	Likely Benign	0.1	0.76	Ambiguous	0.54	Ambiguous	-0.06	Likely Benign	-4.39	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	5.51	Benign	0.01	Affected			2	1	0.3	23.04
c.98A>G	Q33R 2D AIThe SynGAP1 missense variant Q33R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The predictions do not contradict ClinVar status, as ClinVar contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.436712	Uncertain	0.342	0.860	0.375							0.561	Likely Benign	0.171	Likely Benign	Likely Benign	0.035	Likely Benign	0.1936	0.2773											-0.82	Neutral	0.084	Benign	0.046	Benign	4.20	Benign	0.00	Affected			1	1	-1.0	28.06
c.1127G>A	G376D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G376D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The remaining tools—Rosetta, Foldetta, premPS, and ESM1b—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an uncertain stability change. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625							-7.125	In-Between	0.569	Likely Pathogenic	Likely Benign	0.572	Likely Pathogenic	0.1938	0.1235		3.10	Destabilizing	1.1	-1.08	Ambiguous	1.01	Ambiguous	0.52	Ambiguous	-1.05	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.09	Tolerated			1	-1	-3.1	58.04
c.1297G>T	A433S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A433S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign or likely benign. Only polyPhen‑2 (HumDiv) predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely benign classification; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence points to a benign impact for A433S, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000							-3.861	Likely Benign	0.077	Likely Benign	Likely Benign	0.077	Likely Benign	0.1938	0.3975		-0.04	Likely Benign	0.0	0.41	Likely Benign	0.19	Likely Benign	-0.21	Likely Benign	0.35	Neutral	0.597	Possibly Damaging	0.391	Benign	3.46	Benign	0.28	Tolerated			1	1	-2.6	16.00
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	0.554	Likely Pathogenic	0.1938	0.3553		0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			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	0.554	Likely Pathogenic	0.1938	0.3553		0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			3	2	0.0	-14.03
c.2989G>C	A997P 2D AIThe SynGAP1 missense variant A997P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.948624	Binding	0.273	0.901	0.500							-2.014	Likely Benign	0.074	Likely Benign	Likely Benign	0.092	Likely Benign	0.1938	0.5294											-1.17	Neutral	0.001	Benign	0.003	Benign	4.11	Benign	0.00	Affected			1	-1	-3.4	26.04
c.3524G>A	R1175Q 2D AIThe SynGAP1 missense variant R1175Q is reported in gnomAD (ID 6‑33444559‑G‑A) but has no ClinVar entry. Functional 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, and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta (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 because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.589347	Binding	0.545	0.732	0.375				6-33444559-G-A	1	6.20e-7	-3.968	Likely Benign	0.529	Ambiguous	Likely Benign	0.328	Likely Benign	0.1938	0.1835											-0.76	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	5.39	Benign	0.00	Affected	4.32	2	1	1	1.0	-28.06
c.3710A>T	Y1237F 2D AIThe SynGAP1 missense variant Y1237F is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus confirms a likely pathogenic prediction, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for Y1237F. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125							-4.494	Likely Benign	0.864	Likely Pathogenic	Ambiguous	0.268	Likely Benign	0.1938	0.2424											-3.12	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.55	Pathogenic	0.00	Affected			7	3	4.1	-16.00
c.2487G>C	E829D 2D AIThe SynGAP1 missense variant E829D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, 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 preponderance of evidence from multiple independent predictors indicates that E829D 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		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375							-4.015	Likely Benign	0.091	Likely Benign	Likely Benign	0.066	Likely Benign	0.1939	0.4964											-1.89	Neutral	0.217	Benign	0.121	Benign	2.40	Pathogenic	0.00	Affected			3	2	0.0	-14.03
c.2487G>T	E829D 2D AIThe SynGAP1 missense variant E829D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, 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 preponderance of evidence from multiple independent predictors indicates that E829D 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		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375							-4.015	Likely Benign	0.091	Likely Benign	Likely Benign	0.066	Likely Benign	0.1939	0.4964											-1.89	Neutral	0.217	Benign	0.121	Benign	2.40	Pathogenic	0.00	Affected			3	2	0.0	-14.03
c.1456G>A	E486K 2D 3DClick to see structure in 3D Viewer AISynGAP1 E486K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a benign effect. Because the predictions are split evenly and the high‑accuracy tools are contradictory, the variant’s impact remains uncertain; thus, the variant is most likely pathogenic based on the high‑accuracy predictions, a conclusion that contradicts its ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125	Uncertain		2				-14.545	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.435	Likely Benign	0.1940	0.6392		0.06	Likely Benign	0.1	0.37	Likely Benign	0.22	Likely Benign	0.41	Likely Benign	-3.58	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	3.40	Benign	0.12	Tolerated	3.37	35	0	1	-0.4	-0.94	206.8	52.1	-0.3	0.1	0.2	0.0	X			X				Uncertain	Glu486 is located in an α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. It is adjacent to the arginine finger (Arg485) and is expected to closely interact with Ras. The residue swap could affect complex formation with the GTPase and its activation. In the WT simulations, the carboxylate group of Glu486 forms salt bridges with Arg485 and Arg475 on the preceding α-helix (res. Ala461-Phe476). In the variant simulations, Lys486 does not form any specific interactions. Although the amino group of the Lys486 side chain cannot form these salt bridges, no negative effects on the protein structure are observed. Nevertheless, the potential role of Glu486 in SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations, and no definite conclusions can be drawn.
c.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	0.884	Likely Pathogenic	0.1940	0.4570		5.82	Destabilizing	0.6	7.70	Destabilizing	6.76	Destabilizing	1.13	Destabilizing	-4.15	Deleterious	0.987	Probably Damaging	0.844	Possibly Damaging	-1.39	Pathogenic	0.01	Affected			1	-1	-3.4	26.04
c.1855A>C	T619P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T619P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX and SIFT, while pathogenic predictions are made by REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools report uncertainty: premPS and AlphaMissense‑Optimized. High‑accuracy assessments further clarify the variant’s impact: 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 calculations, also predicts pathogenicity. Overall, the majority of evidence points to a pathogenic effect for T619P, and 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	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000							-12.879	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous	0.860	Likely Pathogenic	0.1940	0.3806		0.43	Likely Benign	0.2	4.81	Destabilizing	2.62	Destabilizing	0.82	Ambiguous	-5.51	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.39	Pathogenic	0.09	Tolerated			0	-1	-0.9	-3.99
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	0.1940	0.5197											-1.25	Neutral	0.991	Probably Damaging	0.982	Probably Damaging	2.69	Benign	0.02	Affected			1	1	-2.7	27.03
c.413A>C	K138T 2D AIThe SynGAP1 missense variant K138T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; 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, with no high‑accuracy consensus supporting pathogenicity. Thus, the variant is most likely benign based on current computational 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.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375							-5.143	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic	0.195	Likely Benign	0.1940	0.2806											-3.45	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.01	Affected			0	-1	3.2	-27.07
c.2590G>C	A864P 2D AIThe SynGAP1 missense variant A864P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250							-3.665	Likely Benign	0.093	Likely Benign	Likely Benign	0.067	Likely Benign	0.1941	0.5746											-0.12	Neutral	0.586	Possibly Damaging	0.211	Benign	2.60	Benign	0.09	Tolerated			1	-1	-3.4	26.04
c.317G>C	R106T 2D AIThe SynGAP1 missense variant R106T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Separately, the high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while AlphaMissense‑Optimized remains uncertain and Foldetta data are missing. Based on the overall pattern of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875							-4.197	Likely Benign	0.950	Likely Pathogenic	Ambiguous	0.229	Likely Benign	0.1941	0.4742											-2.30	Neutral	0.004	Benign	0.002	Benign	3.67	Benign	0.00	Affected			-1	-1	3.8	-55.08
c.2789C>A	P930H 2D AIThe SynGAP1 missense variant P930H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors and high‑accuracy tools indicates that P930H is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375							-9.824	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.497	Likely Benign	0.1942	0.4392											-6.44	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0	-2	-1.6	40.02
c.2927T>A	F976Y 2D AIThe SynGAP1 missense variant F976Y is not 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 not available. 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		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625							-3.902	Likely Benign	0.225	Likely Benign	Likely Benign	0.172	Likely Benign	0.1942	0.2257											-0.50	Neutral	0.925	Possibly Damaging	0.529	Possibly Damaging	4.11	Benign	0.80	Tolerated			7	3	-4.1	16.00
c.1424G>C	R475P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R475P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: benign‑predicting algorithms are not present, while pathogenic‑predicting tools—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—all classify the substitution as pathogenic. High‑accuracy assessments corroborate this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. Consequently, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.382696	Uncertain	0.852	0.261	0.000							-16.637	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.835	Likely Pathogenic	0.1943	0.3295		2.93	Destabilizing	0.4	5.40	Destabilizing	4.17	Destabilizing	1.02	Destabilizing	-6.53	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.00	Affected			0	-2	2.9	-59.07
c.2886C>A	H962Q 2D AIThe SynGAP1 missense variant H962Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.984483	Binding	0.369	0.886	0.750							-8.161	Likely Pathogenic	0.130	Likely Benign	Likely Benign	0.114	Likely Benign	0.1943	0.3844											-1.04	Neutral	0.325	Benign	0.045	Benign	4.19	Benign	0.06	Tolerated			3	0	-0.3	-9.01
c.2886C>G	H962Q 2D AIThe SynGAP1 missense variant H962Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome. 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 effect. There is no ClinVar entry to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.984483	Binding	0.369	0.886	0.750							-8.161	Likely Pathogenic	0.130	Likely Benign	Likely Benign	0.114	Likely Benign	0.1943	0.3844											-1.04	Neutral	0.325	Benign	0.045	Benign	4.19	Benign	0.06	Tolerated			3	0	-0.3	-9.01
c.743G>C	R248P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R248P is listed in ClinVar as Pathogenic (ClinVar ID 1065478.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the overwhelming consensus of pathogenic predictions and the high‑accuracy tool results, the variant is most likely pathogenic, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.267126	Uncertain	0.781	0.346	0.250	Likely Pathogenic		1				-10.751	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.848	Likely Pathogenic	0.1943	0.4528		3.09	Destabilizing	0.6	8.87	Destabilizing	5.98	Destabilizing	1.21	Destabilizing	-5.97	Deleterious	0.998	Probably Damaging	0.878	Possibly Damaging	5.64	Benign	0.00	Affected	3.41	14	0	-2	2.9	-59.07	223.8	126.6	0.0	0.0	-0.2	0.1	X	X						Potentially Pathogenic	The guanidinium group of Arg248, located on an α helix (residues Ala236-Val250), forms two very stable salt bridges with Asp255 (from a short α helical section, res. Lys254-Asn256) and Glu244 (from a nearby loop) in the WT simulations. In the variant simulations, the pyrrolidine side chain of Pro248 cannot form any salt bridges, which could negatively affect the tertiary structure assembly of the PH domain. Additionally, Pro248 lacks a free amide group needed for hydrogen bonding with the backbone carbonyl group of Asn245, disrupting the continuity of the α helix.
c.1840T>A	Y614N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y614N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas the majority of other in silico predictors (Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; FoldX is inconclusive and is treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for Y614N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000							-13.004	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	0.471	Likely Benign	0.1944	0.0573		1.32	Ambiguous	0.5	3.16	Destabilizing	2.24	Destabilizing	1.58	Destabilizing	-8.86	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.42	Benign	0.06	Tolerated			-2	-2	-2.2	-49.07
c.2144C>T	P715L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Because the majority of consensus and individual predictors indicate pathogenicity, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for P715L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000							-12.207	Likely Pathogenic	0.764	Likely Pathogenic	Likely Benign	0.318	Likely Benign	0.1944	0.5105		1.43	Ambiguous	0.1	0.06	Likely Benign	0.75	Ambiguous	0.58	Ambiguous	-9.10	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.39	Benign	0.01	Affected			-3	-3	5.4	16.04
c.2264T>C	M755T 2D AIThe SynGAP1 missense variant M755T is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts benign. No tool predicts pathogenicity; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates majority votes from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta data are not available. Overall, the computational evidence overwhelmingly suggests the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.783855	Binding	0.336	0.873	0.375							-4.116	Likely Benign	0.358	Ambiguous	Likely Benign	0.040	Likely Benign	0.1944	0.1767											-1.23	Neutral	0.159	Benign	0.053	Benign	2.65	Benign	0.19	Tolerated			-1	-1	-2.6	-30.09
c.2461T>C	C821R 2D AIThe SynGAP1 missense variant C821R is not 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. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, while three suggest 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.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750							-3.997	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic	0.183	Likely Benign	0.1944	0.1746											-2.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			-4	-3	-7.0	53.05
c.3955G>A	A1319T 2D AIThe SynGAP1 missense variant A1319T is reported in gnomAD (variant ID 6‑33451829‑G‑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, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts a benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, SGM‑Consensus is benign, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence supports a benign impact for A1319T, 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		0.842060	Disordered	0.960481	Binding	0.454	0.851	0.750				6-33451829-G-A			-4.861	Likely Benign	0.076	Likely Benign	Likely Benign	0.097	Likely Benign	0.1944	0.7174											-0.30	Neutral	0.917	Possibly Damaging	0.500	Possibly Damaging	4.13	Benign	0.03	Affected	3.77	5	0	1	-2.5	30.03
c.17C>A	A6D 2D AIThe SynGAP1 missense variant A6D is reported in gnomAD (ID 6‑33420281‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.566480	Disordered	0.549054	Binding	0.377	0.920	0.875				6-33420281-C-A			-3.340	Likely Benign	0.210	Likely Benign	Likely Benign	0.211	Likely Benign	0.1945	0.2530											0.34	Neutral	0.117	Benign	0.010	Benign	4.07	Benign	0.00	Affected	4.32	1	-2	0	-5.3	44.01
c.2384C>A	P795H 2D AIThe SynGAP1 missense variant P795H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic outcome. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875							-7.717	In-Between	0.121	Likely Benign	Likely Benign	0.069	Likely Benign	0.1947	0.5184											-0.61	Neutral	0.898	Possibly Damaging	0.477	Possibly Damaging	4.24	Benign	0.05	Affected			0	-2	-1.6	40.02
c.3305C>G	A1102G 2D AIThe SynGAP1 A1102G missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as “Likely Benign,” and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.915074	Disordered	0.962659	Binding	0.388	0.859	0.875							-3.070	Likely Benign	0.078	Likely Benign	Likely Benign	0.060	Likely Benign	0.1947	0.4958											0.39	Neutral	0.000	Benign	0.001	Benign	2.30	Pathogenic	0.14	Tolerated			1	0	-2.2	-14.03
c.3794G>C	R1265T 2D AIThe SynGAP1 missense variant R1265T is reported in ClinVar as Pathogenic (ClinVar ID 522047.0) and is not found in gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions supports a pathogenic classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000	Likely Pathogenic		1				-10.129	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.529	Likely Pathogenic	0.1947	0.4618											-4.97	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.29	Pathogenic	0.00	Affected	3.77	5	-1	-1	3.8	-55.08
c.853T>C	C285R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C285R is 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 FoldX, which scores the variant as benign. All other evaluated predictors—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Consequently, the preponderance of evidence points to a pathogenic effect for C285R, 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	C2	0.144935	Structured	0.375400	Uncertain	0.946	0.250	0.000							-9.127	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.583	Likely Pathogenic	0.1947	0.1453		-0.47	Likely Benign	0.2	-0.63	Ambiguous	-0.55	Ambiguous	1.53	Destabilizing	-9.66	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.04	Affected			-4	-3	-7.0	53.05
c.1355T>G	V452G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V452G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. AlphaMissense‑Optimized remains uncertain. Overall, the preponderance of evidence indicates that V452G is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000							-13.410	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.570	Likely Pathogenic	0.1948	0.2567		3.70	Destabilizing	0.1	3.37	Destabilizing	3.54	Destabilizing	2.46	Destabilizing	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.17	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.1840T>C	Y614H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y614H is not 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, whereas a majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and Rosetta. Tools with uncertain or inconclusive results (FoldX, Foldetta, premPS) are not considered evidence for either side. 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, remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000							-9.678	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.397	Likely Benign	0.1948	0.0373		1.17	Ambiguous	0.5	2.38	Destabilizing	1.78	Ambiguous	0.91	Ambiguous	-4.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.58	Benign	0.27	Tolerated			0	2	-1.9	-26.03
c.2187C>A	N729K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729K has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus call (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. Tools with uncertain or mixed results are Foldetta (protein‑folding stability) and Rosetta. High‑accuracy assessments: AlphaMissense‑Optimized reports a benign effect; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign; Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not contradict the current ClinVar status, which contains no report for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625							-5.101	Likely Benign	0.648	Likely Pathogenic	Likely Benign	0.036	Likely Benign	0.1948	0.3612		-0.03	Likely Benign	0.1	1.92	Ambiguous	0.95	Ambiguous	0.12	Likely Benign	-1.39	Neutral	0.109	Benign	0.033	Benign	3.51	Benign	0.47	Tolerated			1	0	-0.4	14.07
c.2187C>G	N729K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N729K has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus call (Likely Benign). Only AlphaMissense‑Default predicts a pathogenic outcome. Tools with uncertain or mixed results are Foldetta (protein‑folding stability) and Rosetta. High‑accuracy assessments: AlphaMissense‑Optimized reports a benign effect; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign; Foldetta’s stability prediction is inconclusive. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not contradict the current ClinVar status, which contains no report for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.426547	Uncertain	0.651	0.583	0.625							-5.101	Likely Benign	0.648	Likely Pathogenic	Likely Benign	0.036	Likely Benign	0.1948	0.3612		-0.03	Likely Benign	0.1	1.92	Ambiguous	0.95	Ambiguous	0.12	Likely Benign	-1.39	Neutral	0.109	Benign	0.033	Benign	3.51	Benign	0.47	Tolerated			1	0	-0.4	14.07
c.1844C>T	P615L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P615L 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 premPS and Rosetta, whereas the remaining tools—REVEL, FoldX, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, PROVEAN, and the SGM Consensus—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity, and Foldetta yields an uncertain result. Taken together, the overwhelming majority of computational evidence indicates that P615L is likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.236433	Structured	0.179032	Uncertain	0.879	0.255	0.000							-11.884	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.699	Likely Pathogenic	0.1949	0.4692		2.03	Destabilizing	0.4	-0.01	Likely Benign	1.01	Ambiguous	0.50	Likely Benign	-9.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.13	Pathogenic	0.04	Affected			-3	-3	5.4	16.04
c.521T>C	M174T 2D AIThe SynGAP1 missense variant M174T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375							-9.174	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.286	Likely Benign	0.1949	0.2334											-3.12	Deleterious	0.244	Benign	0.049	Benign	4.08	Benign	0.01	Affected			-1	-1	-2.6	-30.09
c.1705T>A	F569I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569I is not listed in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classifies the substitution as pathogenic. No predictor reports a benign outcome, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000							-15.362	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.903	Likely Pathogenic	0.1950	0.1973		3.75	Destabilizing	0.2	4.23	Destabilizing	3.99	Destabilizing	1.51	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.31	Pathogenic	0.01	Affected			1	0	1.7	-34.02
c.2755C>A	Q919K 2D AIThe SynGAP1 missense variant Q919K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only polyPhen‑2 HumDiv flags it as pathogenic, while AlphaMissense‑Default remains uncertain. 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. Taken together, the majority of evidence supports a benign interpretation, 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		0.618285	Disordered	0.911223	Binding	0.299	0.841	0.250							-4.357	Likely Benign	0.347	Ambiguous	Likely Benign	0.125	Likely Benign	0.1950	0.4000											-1.43	Neutral	0.771	Possibly Damaging	0.412	Benign	2.54	Benign	0.21	Tolerated			1	1	-0.4	0.04
c.3886G>A	E1296K 2D AIThe SynGAP1 missense variant E1296K is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM; pathogenic predictions come from PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus (majority vote of 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 points toward a benign impact, with no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625							-3.435	Likely Benign	0.713	Likely Pathogenic	Likely Benign	0.136	Likely Benign	0.1951	0.6138											-2.80	Deleterious	0.241	Benign	0.210	Benign	2.65	Benign	0.05	Affected			0	1	-0.4	-0.94
c.3512C>A	A1171D 2D AIThe SynGAP1 missense variant A1171D is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” and Foldetta results are unavailable. Overall, the balance of evidence from multiple independent predictors and the SGM‑Consensus points to a benign impact for A1171D. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500							-3.897	Likely Benign	0.814	Likely Pathogenic	Ambiguous	0.312	Likely Benign	0.1952	0.2494											-0.80	Neutral	0.611	Possibly Damaging	0.326	Benign	5.34	Benign	0.02	Affected			0	-2	-5.3	44.01
c.1461C>A	N487K 2D AIThe SynGAP1 missense variant N487K lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. The remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other stability predictions are available. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently absent. 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							-13.520	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.489	Likely Benign	0.1953	0.2721		1.10	Ambiguous	0.9	1.28	Ambiguous	1.19	Ambiguous	0.80	Ambiguous	-5.97	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.72	Benign	0.01	Affected			1	0	-0.4	14.07
c.1461C>G	N487K 2D AIThe SynGAP1 missense variant N487K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely disagree: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑related methods (FoldX, Rosetta, premPS, Foldetta) yield uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125							-13.520	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.488	Likely Benign	0.1953	0.2721		1.10	Ambiguous	0.9	1.28	Ambiguous	1.19	Ambiguous	0.80	Ambiguous	-5.97	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.72	Benign	0.01	Affected			1	0	-0.4	14.07
c.1572C>G	C524W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524W is not reported in ClinVar and is absent from gnomAD. Prediction tools uniformly indicate a deleterious effect: benign predictions are absent, while pathogenic predictions are made by REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the consensus of all available predictions, the variant 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	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125							-12.351	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.675	Likely Pathogenic	0.1953	0.3920		3.03	Destabilizing	1.2	9.88	Destabilizing	6.46	Destabilizing	0.93	Ambiguous	-10.94	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.41	Pathogenic	0.00	Affected			-8	-2	-3.4	83.07
c.3158G>A	S1053N 2D AIThe SynGAP1 missense variant S1053N is reported in gnomAD (variant ID 6‑33443710‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus also indicates a likely benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, 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		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875				6-33443710-G-A	1	6.21e-7	-6.282	Likely Benign	0.120	Likely Benign	Likely Benign	0.208	Likely Benign	0.1953	0.4605											-0.54	Neutral	0.625	Possibly Damaging	0.193	Benign	5.30	Benign	0.34	Tolerated	3.77	5	1	1	-2.7	27.03
c.3451T>C	S1151P 2D AIThe SynGAP1 missense variant S1151P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are not available. Overall, the consensus of the available predictions indicates that the variant is most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.805072	Binding	0.394	0.839	0.625							-3.031	Likely Benign	0.298	Likely Benign	Likely Benign	0.123	Likely Benign	0.1953	0.5320											-1.47	Neutral	0.995	Probably Damaging	0.892	Possibly Damaging	2.67	Benign	0.11	Tolerated			1	-1	-0.8	10.04
c.733A>G	N245D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N245D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, SIFT, and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools, premPS and ESM1b, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (six pathogenic vs five benign) and the consensus of high‑accuracy methods lean toward a pathogenic interpretation. 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.		PH	0.454136	Structured	0.315864	Uncertain	0.831	0.351	0.000							-7.847	In-Between	0.998	Likely Pathogenic	Likely Pathogenic	0.712	Likely Pathogenic	0.1953	0.4599		0.27	Likely Benign	0.0	0.09	Likely Benign	0.18	Likely Benign	0.79	Ambiguous	-3.62	Deleterious	0.982	Probably Damaging	0.679	Possibly Damaging	5.84	Benign	0.13	Tolerated			2	1	0.0	0.98
c.1732G>A	E578K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E578K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, and SIFT, whereas polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default predict a pathogenic outcome. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, AlphaMissense‑Optimized remains Uncertain, and Foldetta predicts a benign effect. Overall, the majority of tools (seven benign vs. five pathogenic) suggest a benign impact, and this assessment does not contradict the absence of ClinVar evidence. Thus, the variant is most likely benign based on the current predictions, with no conflicting ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.020971	Uncertain	0.902	0.240	0.000							-13.391	Likely Pathogenic	0.870	Likely Pathogenic	Ambiguous	0.450	Likely Benign	0.1954	0.5480		0.07	Likely Benign	0.1	-0.19	Likely Benign	-0.06	Likely Benign	-0.27	Likely Benign	-1.65	Neutral	0.996	Probably Damaging	0.987	Probably Damaging	-1.30	Pathogenic	0.49	Tolerated			0	1	-0.4	-0.94
c.3134C>A	A1045D 2D AIThe SynGAP1 missense variant A1045D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus all indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the variant as benign. AlphaMissense‑Optimized also predicts a benign outcome, whereas AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” No tools predict pathogenicity. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective predictions strongly suggest that A1045D is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.975609	Disordered	0.948874	Binding	0.352	0.882	0.750							-5.734	Likely Benign	0.418	Ambiguous	Likely Benign	0.066	Likely Benign	0.1954	0.2102											-1.00	Neutral	0.411	Benign	0.172	Benign	2.64	Benign	0.16	Tolerated			0	-2	-5.3	44.01
c.2547T>A	D849E 2D AIThe SynGAP1 missense variant D849E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. 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, was not available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.554191	Binding	0.319	0.813	0.500							-2.911	Likely Benign	0.089	Likely Benign	Likely Benign	0.087	Likely Benign	0.1955	0.7819											-0.55	Neutral	0.393	Benign	0.187	Benign	4.25	Benign	0.00	Affected			3	2	0.0	14.03
c.2547T>G	D849E 2D AIThe SynGAP1 missense variant D849E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. 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 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		0.712013	Disordered	0.554191	Binding	0.319	0.813	0.500							-2.911	Likely Benign	0.089	Likely Benign	Likely Benign	0.087	Likely Benign	0.1955	0.7819											-0.55	Neutral	0.393	Benign	0.187	Benign	4.25	Benign	0.00	Affected			3	2	0.0	14.03
c.3959C>A	P1320H 2D AIThe SynGAP1 missense variant P1320H is listed in gnomAD (ID 6‑33451833‑C‑A) and has no ClinVar entry. Functional 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 as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750				6-33451833-C-A	2	1.29e-6	-6.296	Likely Benign	0.136	Likely Benign	Likely Benign	0.114	Likely Benign	0.1955	0.5461											-1.05	Neutral	0.998	Probably Damaging	0.990	Probably Damaging	4.17	Benign	0.00	Affected	3.77	5	-2	0	-1.6	40.02
c.3976C>A	P1326T 2D AIThe SynGAP1 missense variant P1326T is reported in gnomAD (ID 6‑33451850‑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, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the same four high‑accuracy tools) is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that P1326T is most likely benign, and this assessment does not contradict any ClinVar classification because no ClinVar variant is listed. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875				6-33451850-C-A			-5.755	Likely Benign	0.117	Likely Benign	Likely Benign	0.135	Likely Benign	0.1955	0.5517											-0.26	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.71	Benign	0.00	Affected	3.77	5	-1	0	0.9	3.99
c.2884C>A	H962N 2D AIThe SynGAP1 missense variant H962N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Based on the preponderance of 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		0.991070	Disordered	0.984483	Binding	0.369	0.886	0.750							-8.481	Likely Pathogenic	0.098	Likely Benign	Likely Benign	0.058	Likely Benign	0.1957	0.3216											-0.61	Neutral	0.174	Benign	0.045	Benign	4.18	Benign	0.24	Tolerated			2	1	-0.3	-23.04
c.3512C>G	A1171G 2D AIThe SynGAP1 missense variant A1171G (Ala→Gly at residue 1171) is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect, and no tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome, while Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500							-3.487	Likely Benign	0.286	Likely Benign	Likely Benign	0.141	Likely Benign	0.1957	0.3201											-0.60	Neutral	0.245	Benign	0.138	Benign	5.38	Benign	0.08	Tolerated			1	0	-2.2	-14.03
c.1760G>C	R587T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R587T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT and AlphaMissense‑Optimized, whereas a majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. Uncertain predictions from FoldX, Rosetta, Foldetta, and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R587T, which does not contradict the ClinVar “Uncertain” classification but suggests that the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.077330	Uncertain	0.862	0.216	0.000	Uncertain		1				-9.697	Likely Pathogenic	0.784	Likely Pathogenic	Likely Benign	0.603	Likely Pathogenic	0.1958	0.4578		1.14	Ambiguous	0.2	0.74	Ambiguous	0.94	Ambiguous	0.98	Ambiguous	-4.71	Deleterious	0.998	Probably Damaging	0.847	Possibly Damaging	-1.19	Pathogenic	0.08	Tolerated	3.37	35	-1	-1	3.8	-55.08	227.2	87.4	0.0	0.0	0.5	0.1		X						Potentially Pathogenic	The guanidinium group of Arg587, located on an α helix (res. Glu582-Met603), is constantly rotating and breaking/forming multiple hydrogen bonds and/or salt bridges at the surface intersection of α helices in the WT simulations. The positively charged Arg587 side chain can form a salt bridge with either the carboxylate group of Asp583 or Asp586 in the same helix, or with Glu480 on the opposing short helical loop structure (res. Glu480-Leu482).Importantly, the Arg587 side chain also hydrogen bonds with the backbone carbonyl groups of Ala634 and Asn635, as well as the carboxamide group of Asn635 at the end of another α helix (res. Asp616-Phe636). However, in the variant simulations, the neutral hydroxyl group of the Thr587 side chain is unable to form these salt bridges. Due to its smaller size, it also does not form the hydrogen bonds that the Arg587 side chain could. Instead, the hydroxyl group of Thr587 hydrogen bonds with the backbone carbonyl group of Asp583, which could weaken the integrity of the α helix, although this is not observed in the simulations.Overall, the residue swap could weaken the tertiary structure assembly and negatively affect the overall protein folding process.
c.2366C>T	P789L 2D AIThe SynGAP1 P789L missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence (five pathogenic vs. three benign predictions, with the SGM Consensus supporting pathogenicity) indicates that P789L 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.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750							-4.623	Likely Benign	0.457	Ambiguous	Likely Benign	0.303	Likely Benign	0.1958	0.4866											-5.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.02	Pathogenic	0.00	Affected			-3	-3	5.4	16.04
c.2495A>C	Q832P 2D AIThe SynGAP1 missense variant Q832P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.619913	Binding	0.290	0.877	0.375							-1.882	Likely Benign	0.066	Likely Benign	Likely Benign	0.142	Likely Benign	0.1959	0.4368											-1.07	Neutral	0.002	Benign	0.005	Benign	2.70	Benign	0.05	Affected			0	-1	1.9	-31.01
c.3435C>A	N1145K 2D AIThe SynGAP1 missense variant N1145K is not 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, 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		0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000							-2.545	Likely Benign	0.814	Likely Pathogenic	Ambiguous	0.440	Likely Benign	0.1959	0.6018											-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	5.50	Benign	0.03	Affected			1	0	-0.4	14.07
c.3435C>G	N1145K 2D AIThe SynGAP1 missense variant N1145K is not 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 impact. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000							-2.545	Likely Benign	0.814	Likely Pathogenic	Ambiguous	0.440	Likely Benign	0.1959	0.6018											-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	5.50	Benign	0.03	Affected			1	0	-0.4	14.07
c.2240T>G	V747G 2D AIThe SynGAP1 missense variant V747G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that V747G is most likely benign, and this conclusion does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.816150	Disordered	0.594069	Binding	0.343	0.873	0.750							-3.883	Likely Benign	0.188	Likely Benign	Likely Benign	0.069	Likely Benign	0.1960	0.2374											-1.22	Neutral	0.589	Possibly Damaging	0.917	Probably Damaging	2.56	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.466T>A	F156I 2D AIThe SynGAP1 missense variant F156I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500							-10.505	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic	0.194	Likely Benign	0.1960	0.1938											-2.38	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.99	Benign	0.00	Affected			1	0	1.7	-34.02
c.1718G>C	R573P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R573P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic or likely pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic impact. Based on the uniform predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.032433	Uncertain	0.934	0.235	0.000							-16.684	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.831	Likely Pathogenic	0.1961	0.3239		5.76	Destabilizing	1.1	8.58	Destabilizing	7.17	Destabilizing	1.21	Destabilizing	-5.78	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.47	Pathogenic	0.01	Affected			0	-2	2.9	-59.07
c.1942T>C	F648L 2D AISynGAP1 missense variant F648L is listed in ClinVar with an uncertain significance (ClinVar ID 3383902.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b—consistently predict pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic change. Taken together, the preponderance of evidence points to a pathogenic impact for F648L, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000	Uncertain		1				-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.468	Likely Benign	0.1961	0.3126		2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			2	0	1.0	-34.02
c.1944C>A	F648L 2D AIThe SynGAP1 missense variant F648L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while the remaining 12 tools—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic effect. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic; and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic. Because the majority of evidence points to a deleterious impact and there is no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000							-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.319	Likely Benign	0.1961	0.3126		2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			2	0	1.0	-34.02
c.1944C>G	F648L 2D AIThe SynGAP1 missense variant F648L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b all indicate pathogenicity, and the SGM Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000							-9.296	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.319	Likely Benign	0.1961	0.3126		2.71	Destabilizing	0.8	2.08	Destabilizing	2.40	Destabilizing	1.04	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.45	Benign	0.08	Tolerated			2	0	1.0	-34.02
c.2942G>A	G981D 2D AIThe SynGAP1 missense variant G981D is not reported in ClinVar and is absent from 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, 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. Taken together, the balance of evidence leans toward a benign interpretation; there is no ClinVar entry to contradict 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.	Likely Benign		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625							-5.280	Likely Benign	0.945	Likely Pathogenic	Ambiguous	0.159	Likely Benign	0.1961	0.2868											-1.64	Neutral	1.000	Probably Damaging	0.985	Probably Damaging	3.75	Benign	0.00	Affected			1	-1	-3.1	58.04
c.404G>T	R135L 2D AIThe SynGAP1 missense variant R135L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy tools, support a pathogenic classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250							-7.372	In-Between	0.976	Likely Pathogenic	Likely Pathogenic	0.164	Likely Benign	0.1962	0.4727											-3.61	Deleterious	0.308	Benign	0.122	Benign	3.70	Benign	0.01	Affected			-3	-2	8.3	-43.03
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	0.465	Likely Benign	0.1962	0.3393		0.48	Likely Benign	0.3	0.84	Ambiguous	0.66	Ambiguous	0.33	Likely Benign	-1.40	Neutral	0.990	Probably Damaging	0.681	Possibly Damaging	5.63	Benign	0.19	Tolerated			1	1	-2.6	16.00
c.1261G>C	A421P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A421P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL, FATHMM, and polyPhen‑2 HumVar, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also indicates Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, reports a pathogenic effect. Taken together, the overwhelming majority of evidence points to a pathogenic impact for A421P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000							-13.126	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.371	Likely Benign	0.1963	0.3343		4.51	Destabilizing	0.2	8.77	Destabilizing	6.64	Destabilizing	1.17	Destabilizing	-4.31	Deleterious	0.855	Possibly Damaging	0.420	Benign	3.39	Benign	0.04	Affected			1	-1	-3.4	26.04
c.2740G>C	D914H 2D AIThe SynGAP1 missense variant D914H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) support a benign classification. This consensus does not contradict ClinVar status, as no ClinVar entry exists for this variant. Thus, based on current computational evidence, the D914H variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250							-3.755	Likely Benign	0.651	Likely Pathogenic	Likely Benign	0.184	Likely Benign	0.1963	0.8451											-1.26	Neutral	1.000	Probably Damaging	0.993	Probably Damaging	2.74	Benign	0.01	Affected			1	-1	0.3	22.05
c.2995T>C	S999P 2D AIThe SynGAP1 missense variant S999P is not 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; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for S999P, 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		0.834292	Disordered	0.950682	Binding	0.262	0.897	0.625							-2.279	Likely Benign	0.095	Likely Benign	Likely Benign	0.111	Likely Benign	0.1963	0.6268											-1.05	Neutral	0.966	Probably Damaging	0.773	Possibly Damaging	2.65	Benign	0.04	Affected			1	-1	-0.8	10.04
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	0.1963	0.6246											-2.99	Deleterious	0.985	Probably Damaging	0.927	Probably Damaging	3.50	Benign	0.00	Affected			2	1	0.3	23.04
c.604G>A	E202K 2D AIThe SynGAP1 E202K 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Rosetta and Foldetta give uncertain results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta’s stability assessment is uncertain. Overall, more tools (7 vs. 5) predict pathogenicity, and the high‑accuracy consensus leans toward pathogenic. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.363090	Structured	0.429450	Uncertain	0.712	0.415	0.125							-9.011	Likely Pathogenic	0.678	Likely Pathogenic	Likely Benign	0.231	Likely Benign	0.1963	0.6885		-0.24	Likely Benign	0.3	-0.76	Ambiguous	-0.50	Ambiguous	0.10	Likely Benign	-2.55	Deleterious	0.982	Probably Damaging	0.679	Possibly Damaging	4.07	Benign	0.03	Affected			0	1	-0.4	-0.94
c.2900G>T	R967L 2D AIThe SynGAP1 missense variant R967L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443452‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for R967L, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.974374	Disordered	0.969686	Binding	0.340	0.888	0.750	Uncertain		1	6-33443452-G-T	1	6.20e-7	-3.496	Likely Benign	0.164	Likely Benign	Likely Benign	0.123	Likely Benign	0.1964	0.5093											-0.99	Neutral	0.959	Probably Damaging	0.586	Possibly Damaging	4.15	Benign	0.75	Tolerated	4.32	2	-2	-3	8.3	-43.03
c.3049T>G	F1017V 2D AIThe SynGAP1 missense variant F1017V is not 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, PROVEAN) also yields a benign prediction. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for F1017V, and this conclusion does not contradict any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625							-2.517	Likely Benign	0.497	Ambiguous	Likely Benign	0.161	Likely Benign	0.1964	0.2137											-2.97	Deleterious	0.905	Possibly Damaging	0.637	Possibly Damaging	2.51	Benign	0.03	Affected			-1	-1	1.4	-48.04
c.1708G>C	A570P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570P is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: 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 variant as pathogenic. No tool predicts a benign outcome. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000							-15.178	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.832	Likely Pathogenic	0.1965	0.2578		5.21	Destabilizing	0.5	8.45	Destabilizing	6.83	Destabilizing	1.19	Destabilizing	-4.55	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.31	Pathogenic	0.02	Affected			1	-1	-3.4	26.04
c.2903G>A	G968D 2D AIThe SynGAP1 missense variant G968D is catalogued in gnomAD (ID 6‑33443455‑G‑A) but has no ClinVar entry. Across a broad panel of in‑silico predictors, every tool reports a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, so the pathogenic‑prediction group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available for this variant. Consequently, 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.	Likely Benign		0.978316	Disordered	0.961360	Binding	0.327	0.896	0.750				6-33443455-G-A	1	6.20e-7	-5.134	Likely Benign	0.179	Likely Benign	Likely Benign	0.157	Likely Benign	0.1965	0.3243											-0.48	Neutral	0.440	Benign	0.198	Benign	4.19	Benign	0.21	Tolerated	4.32	2	-1	1	-3.1	58.04
c.380G>T	R127L 2D AIThe SynGAP1 missense variant R127L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.711716	Binding	0.333	0.870	0.625							-0.626	Likely Benign	0.643	Likely Pathogenic	Likely Benign	0.127	Likely Benign	0.1965	0.3834											-2.02	Neutral	0.080	Benign	0.012	Benign	3.92	Benign	0.01	Affected			-3	-2	8.3	-43.03
c.434A>C	K145T 2D AIThe SynGAP1 missense variant K145T is not reported in ClinVar and is absent from gnomAD. Computational assessment shows a split: benign predictions from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, whereas pathogenic predictions come from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, classifies the change as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus itself is a high‑confidence prediction; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for K145T. Thus, the variant is most likely pathogenic, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625							-8.519	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.224	Likely Benign	0.1965	0.3611											-3.54	Deleterious	0.247	Benign	0.166	Benign	3.63	Benign	0.00	Affected			0	-1	3.2	-27.07
c.1257G>C	E419D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or inconclusive predictions come from Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain (unavailable). Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000							-7.036	In-Between	0.869	Likely Pathogenic	Ambiguous	0.170	Likely Benign	0.1966	0.4906		0.17	Likely Benign	0.1	0.87	Ambiguous	0.52	Ambiguous	0.48	Likely Benign	-2.40	Neutral	0.995	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.10	Tolerated			3	2	0.0	-14.03
c.1257G>T	E419D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Uncertain or inconclusive predictions come from Foldetta, AlphaMissense‑Optimized, ESM1b, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain (treated as unavailable), the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains uncertain (unavailable). Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000							-7.036	In-Between	0.869	Likely Pathogenic	Ambiguous	0.170	Likely Benign	0.1966	0.4906		0.17	Likely Benign	0.1	0.87	Ambiguous	0.52	Ambiguous	0.48	Likely Benign	-2.40	Neutral	0.995	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.10	Tolerated			3	2	0.0	-14.03
c.2930C>T	A977V 2D AIThe SynGAP1 missense variant A977V is not 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 A977V, and 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		0.882776	Disordered	0.975330	Binding	0.306	0.884	0.625							-3.542	Likely Benign	0.151	Likely Benign	Likely Benign	0.064	Likely Benign	0.1966	0.5727											-1.15	Neutral	0.818	Possibly Damaging	0.457	Possibly Damaging	4.01	Benign	0.01	Affected			0	0	2.4	28.05
c.3086A>C	Q1029P 2D AIThe SynGAP1 missense variant Q1029P is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available for this variant. Overall, the consensus of all available predictions strongly supports a benign impact, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500							-2.940	Likely Benign	0.124	Likely Benign	Likely Benign	0.105	Likely Benign	0.1966	0.4986											-1.23	Neutral	0.005	Benign	0.015	Benign	2.68	Benign	0.15	Tolerated			0	-1	1.9	-31.01
c.3215A>C	K1072T 2D AIThe SynGAP1 missense variant K1072T is not 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 result is benign; Foldetta predictions are unavailable. Overall, the balance of evidence leans toward a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750							-2.557	Likely Benign	0.834	Likely Pathogenic	Ambiguous	0.082	Likely Benign	0.1967	0.4307											-1.31	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.06	Tolerated			0	-1	3.2	-27.07
c.509G>C	R170P 2D AIThe SynGAP1 missense variant R170P is not 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 R170P 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		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250							-9.687	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.386	Likely Benign	0.1967	0.3989											-3.96	Deleterious	0.966	Probably Damaging	0.599	Possibly Damaging	3.86	Benign	0.00	Affected			0	-2	2.9	-59.07
c.2892C>A	H964Q 2D AIThe SynGAP1 missense variant H964Q is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. The only tool with an uncertain call is ESM1b, and no pathogenic predictions are reported. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign; Foldetta results are unavailable. 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		0.990547	Disordered	0.982486	Binding	0.364	0.886	0.750							-7.279	In-Between	0.102	Likely Benign	Likely Benign	0.058	Likely Benign	0.1969	0.3593											-0.38	Neutral	0.000	Benign	0.000	Benign	4.18	Benign	0.07	Tolerated			3	0	-0.3	-9.01
c.2892C>G	H964Q 2D AIThe SynGAP1 missense variant H964Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only uncertain result comes from ESM1b. The high‑accuracy consensus methods also support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the evidence overwhelmingly indicates that H964Q is most likely benign, 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		0.990547	Disordered	0.982486	Binding	0.364	0.886	0.750							-7.279	In-Between	0.102	Likely Benign	Likely Benign	0.058	Likely Benign	0.1969	0.3593											-0.38	Neutral	0.000	Benign	0.000	Benign	4.18	Benign	0.07	Tolerated			3	0	-0.3	-9.01
c.3505G>A	E1169K 2D AISynGAP1 missense variant E1169K is listed in gnomAD (ID 6‑33444540‑G‑A) but has no ClinVar record. Functional prediction tools fall into two groups: benign predictions come from SGM‑Consensus, REVEL, PROVEAN, ESM1b, and FATHMM; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign. Foldetta stability analysis is unavailable. Overall, the evidence is split evenly, with one high‑accuracy tool supporting pathogenicity and the consensus tool supporting benignity. Therefore, the variant’s impact remains uncertain; it is not contradicted by ClinVar status, which has no entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625				6-33444540-G-A	1	6.20e-7	-3.335	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic	0.185	Likely Benign	0.1969	0.6422											-1.81	Neutral	0.997	Probably Damaging	0.898	Possibly Damaging	2.51	Benign	0.00	Affected	3.88	3	1	0	-0.4	-0.94
c.582G>C	E194D 2D AIThe SynGAP1 missense variant E194D is not 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, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” AlphaMissense‑Optimized is uncertain, and 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 based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125							-6.310	Likely Benign	0.883	Likely Pathogenic	Ambiguous	0.079	Likely Benign	0.1969	0.2779											-2.07	Neutral	0.849	Possibly Damaging	0.301	Benign	4.01	Benign	0.04	Affected			3	2	0.0	-14.03
c.582G>T	E194D 2D AIThe SynGAP1 missense variant E194D is not 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, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a “Likely Benign” classification, while AlphaMissense‑Optimized is uncertain. Foldetta stability analysis is 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		0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125							-6.310	Likely Benign	0.883	Likely Pathogenic	Ambiguous	0.079	Likely Benign	0.1969	0.2779											-2.07	Neutral	0.849	Possibly Damaging	0.301	Benign	4.01	Benign	0.04	Affected			3	2	0.0	-14.03
c.939G>C	E313D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E313D is not 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 SIFT, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicating a likely pathogenic effect, and Foldetta yielding an uncertain stability change. Overall, the balance of evidence points to a pathogenic interpretation; 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	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125							-8.309	Likely Pathogenic	0.636	Likely Pathogenic	Likely Benign	0.346	Likely Benign	0.1970	0.4640		0.87	Ambiguous	0.0	0.96	Ambiguous	0.92	Ambiguous	0.60	Ambiguous	-1.66	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.88	Pathogenic	0.14	Tolerated			3	2	0.0	-14.03
c.939G>T	E313D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E313D is not 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 SIFT, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicating a likely pathogenic outcome, and Foldetta yielding an uncertain stability change. Overall, the balance of evidence points to a pathogenic effect for E313D, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125							-8.309	Likely Pathogenic	0.636	Likely Pathogenic	Likely Benign	0.346	Likely Benign	0.1970	0.4640		0.87	Ambiguous	0.0	0.96	Ambiguous	0.92	Ambiguous	0.60	Ambiguous	-1.66	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.88	Pathogenic	0.14	Tolerated			3	2	0.0	-14.03
c.317G>T	R106M 2D AIThe SynGAP1 missense variant R106M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Because the majority of tools (five of nine) predict pathogenicity and the most accurate predictor (AlphaMissense‑Optimized) also indicates pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875							-4.804	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic	0.184	Likely Benign	0.1971	0.4146											-2.65	Deleterious	0.940	Possibly Damaging	0.360	Benign	3.64	Benign	0.00	Affected			0	-1	6.4	-24.99
c.1202G>T	R401L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401L is not reported in ClinVar and is present in gnomAD (ID 6‑33438107‑G‑T). Prediction tools that classify the variant as benign include Rosetta, FATHMM, and premPS, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX alone is available. Based on the preponderance of pathogenic predictions and the corroborating high‑accuracy tools, R401L is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000				6-33438107-G-T	1	6.20e-7	-12.280	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.858	Likely Pathogenic	0.1972	0.4263		-1.52	Ambiguous	0.1	-0.23	Likely Benign	-0.88	Ambiguous	0.22	Likely Benign	-6.42	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	5.44	Benign	0.02	Affected	3.38	27	-2	-3	8.3	-43.03
c.2920G>A	D974N 2D AIThe SynGAP1 missense variant D974N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect. Consensus predictors such as SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and high‑accuracy methods including AlphaMissense‑Optimized all classify the variant as benign. Additional in silico assessments—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—also predict a benign outcome. No tool in the dataset suggests pathogenicity. Protein‑stability analysis via Foldetta is unavailable 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		0.879233	Disordered	0.964377	Binding	0.389	0.897	0.625							-4.051	Likely Benign	0.145	Likely Benign	Likely Benign	0.088	Likely Benign	0.1972	0.7698											-0.35	Neutral	0.144	Benign	0.085	Benign	4.20	Benign	0.09	Tolerated			2	1	0.0	-0.98
c.3644A>C	K1215T 2D AIThe SynGAP1 missense variant K1215T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect; 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	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375							-12.008	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.204	Likely Benign	0.1972	0.2214											-4.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0	-1	3.2	-27.07
c.3964G>A	A1322T 2D AIThe SynGAP1 missense variant A1322T is catalogued in gnomAD (ID 6‑33451838‑G‑A) but has no ClinVar entry. All available in silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic outcome. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method, has no reported result for this variant. Overall, the evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.921040	Binding	0.466	0.825	0.875				6-33451838-G-A			-4.940	Likely Benign	0.077	Likely Benign	Likely Benign	0.079	Likely Benign	0.1972	0.7582											0.51	Neutral	0.000	Benign	0.000	Benign	4.20	Benign	0.27	Tolerated	3.77	5	0	1	-2.5	30.03
c.647A>G	Q216R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q216R is not reported in ClinVar and has no gnomAD entry. Prediction tools that call the variant benign include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while pathogenic calls come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as Benign. Overall, the predictions are split, with a slight edge toward pathogenicity. The variant is therefore most likely pathogenic based on the current computational evidence, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000							-10.149	Likely Pathogenic	0.821	Likely Pathogenic	Ambiguous	0.513	Likely Pathogenic	0.1972	0.2748		-0.42	Likely Benign	0.0	0.09	Likely Benign	-0.17	Likely Benign	-0.01	Likely Benign	-2.70	Deleterious	0.963	Probably Damaging	0.549	Possibly Damaging	6.00	Benign	0.19	Tolerated			1	1	-1.0	28.06
c.701G>C	R234P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R234P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, whereas the majority of evaluated algorithms (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.311558	Uncertain	0.804	0.322	0.000							-10.126	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.826	Likely Pathogenic	0.1972	0.4336		1.33	Ambiguous	0.6	1.36	Ambiguous	1.35	Ambiguous	0.13	Likely Benign	-4.43	Deleterious	0.929	Possibly Damaging	0.519	Possibly Damaging	5.93	Benign	0.04	Affected			0	-2	2.9	-59.07
c.943A>G	N315D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N315D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and FATHMM. The remaining tools (FoldX, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority; and Foldetta predicts a benign stability change. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.118441	Structured	0.379740	Uncertain	0.862	0.253	0.125							-5.667	Likely Benign	0.536	Ambiguous	Likely Benign	0.229	Likely Benign	0.1972	0.4488		1.27	Ambiguous	0.6	-0.30	Likely Benign	0.49	Likely Benign	0.88	Ambiguous	-2.41	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.02	Pathogenic	0.45	Tolerated			2	1	0.0	0.98
c.1987T>C	F663L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663L is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, which scores the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity, while Foldetta’s stability analysis is inconclusive and therefore unavailable. FoldX and Foldetta are treated as unavailable due to uncertain outputs. Based on the overwhelming agreement among pathogenic predictors and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000							-11.996	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.540	Likely Pathogenic	0.1973	0.2936		0.91	Ambiguous	0.1	2.01	Destabilizing	1.46	Ambiguous	1.51	Destabilizing	-5.99	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.07	Benign	0.01	Affected			2	0	1.0	-34.02
c.1989T>A	F663L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, SGM Consensus, premPS, and Rosetta) indicate a pathogenic impact. FoldX‑MD and Rosetta‑based stability calculations are inconclusive, yielding an uncertain Foldetta result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence from consensus and high‑accuracy tools points to a pathogenic effect for F663L. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000							-11.996	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.423	Likely Benign	0.1973	0.2936		0.91	Ambiguous	0.1	2.01	Destabilizing	1.46	Ambiguous	1.51	Destabilizing	-5.99	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.07	Benign	0.01	Affected			2	0	1.0	-34.02
c.1989T>G	F663L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, and the SGM Consensus) indicate a pathogenic impact. FoldX‑MD and Rosetta give conflicting stability results, with FoldX uncertain and Rosetta pathogenic; Foldetta, which integrates both, is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for F663L. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000							-11.996	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.423	Likely Benign	0.1973	0.2936		0.91	Ambiguous	0.1	2.01	Destabilizing	1.46	Ambiguous	1.51	Destabilizing	-5.99	Deleterious	0.999	Probably Damaging	0.976	Probably Damaging	3.07	Benign	0.01	Affected			2	0	1.0	-34.02
c.1483G>A	E495K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E495K is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include FoldX and Foldetta, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools with inconclusive results (Rosetta and premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus also as pathogenic, while Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) indicates a benign effect. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect for E495K, which is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000	Uncertain		1				-11.478	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.869	Likely Pathogenic	0.1974	0.5039		0.15	Likely Benign	0.2	0.66	Ambiguous	0.41	Likely Benign	0.70	Ambiguous	-3.91	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.29	Pathogenic	0.01	Affected	3.37	35	1	0	-0.4	-0.94
c.3715G>T	A1239S 2D AIThe SynGAP1 missense variant A1239S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while SIFT and FATHMM predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and no Foldetta stability data are available. 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.	Likely Benign	Coiled-coil	0.541878	Disordered	0.534779	Binding	0.887	0.542	0.250							-2.847	Likely Benign	0.073	Likely Benign	Likely Benign	0.019	Likely Benign	0.1974	0.4095											-0.95	Neutral	0.003	Benign	0.005	Benign	2.39	Pathogenic	0.00	Affected			1	1	-2.6	16.00
c.1253A>C	K418T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K418T variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, FATHMM, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of tools (10 pathogenic vs. 5 benign) support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar record exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000							-11.994	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.392	Likely Benign	0.1975	0.1894		0.39	Likely Benign	0.1	0.55	Ambiguous	0.47	Likely Benign	0.41	Likely Benign	-5.36	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.37	Benign	0.04	Affected			0	-1	3.2	-27.07
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	0.304	Likely Benign	0.1975	0.3918		1.27	Ambiguous	0.3	1.99	Ambiguous	1.63	Ambiguous	1.00	Destabilizing	-2.75	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			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	0.303	Likely Benign	0.1975	0.3918		1.27	Ambiguous	0.3	1.99	Ambiguous	1.63	Ambiguous	1.00	Destabilizing	-2.75	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			3	2	0.0	-14.03
c.1583C>T	P528L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Because the majority of evidence points to a deleterious effect and no ClinVar annotation exists 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	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000							-13.752	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous	0.555	Likely Pathogenic	0.1975	0.5574		1.31	Ambiguous	0.1	0.61	Ambiguous	0.96	Ambiguous	0.19	Likely Benign	-9.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.48	Pathogenic	0.00	Affected			-3	-3	5.4	16.04
c.3128G>C	R1043T 2D AIThe SynGAP1 missense variant R1043T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978672	Disordered	0.954069	Binding	0.299	0.853	0.625							-3.928	Likely Benign	0.298	Likely Benign	Likely Benign	0.463	Likely Benign	0.1975	0.5513											-1.77	Neutral	0.001	Benign	0.003	Benign	5.39	Benign	0.00	Affected			-1	-1	3.8	-55.08
c.3592T>C	Y1198H 2D AIThe SynGAP1 missense variant Y1198H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and SIFT, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250							-10.394	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.246	Likely Benign	0.1975	0.0373											-2.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.19	Tolerated			0	2	-1.9	-26.03
c.714A>C	E238D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E238D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; the remaining methods (FoldX, Rosetta, Foldetta, premPS, ESM1b) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. The variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status because no ClinVar record exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.194234	Structured	0.332638	Uncertain	0.796	0.326	0.000							-7.861	In-Between	0.995	Likely Pathogenic	Likely Pathogenic	0.691	Likely Pathogenic	0.1975	0.3619		1.25	Ambiguous	0.4	1.72	Ambiguous	1.49	Ambiguous	0.78	Ambiguous	-2.72	Deleterious	0.868	Possibly Damaging	0.504	Possibly Damaging	5.57	Benign	0.05	Affected			3	2	0.0	-14.03
c.714A>T	E238D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E238D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact; the remaining methods (FoldX, Rosetta, Foldetta, premPS, ESM1b) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. The variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status because no ClinVar record exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.194234	Structured	0.332638	Uncertain	0.796	0.326	0.000							-7.861	In-Between	0.995	Likely Pathogenic	Likely Pathogenic	0.691	Likely Pathogenic	0.1975	0.3619		1.25	Ambiguous	0.4	1.72	Ambiguous	1.49	Ambiguous	0.78	Ambiguous	-2.72	Deleterious	0.868	Possibly Damaging	0.504	Possibly Damaging	5.57	Benign	0.05	Affected			3	2	0.0	-14.03
c.1705T>C	F569L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none; all available predictors that provide a verdict classify the variant as pathogenic, with the exception of FoldX and Foldetta, whose results are uncertain and therefore treated as unavailable. The high‑accuracy predictors give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is uncertain and thus not considered evidence. Based on the overwhelming consensus of pathogenic predictions and the lack of contrary evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000							-9.784	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.804	Likely Pathogenic	0.1977	0.2476		0.86	Ambiguous	0.1	2.04	Destabilizing	1.45	Ambiguous	1.28	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.13	Pathogenic	0.05	Affected			2	0	1.0	-34.02
c.1707T>A	F569L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none; all available predictors that provide a verdict classify the variant as pathogenic, with the exception of FoldX and Foldetta, whose results are uncertain and therefore treated as unavailable. The high‑accuracy predictors give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is uncertain and thus not considered evidence. Based on the overwhelming consensus of pathogenic predictions and the lack of contrary evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000							-9.784	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.675	Likely Pathogenic	0.1977	0.2476		0.86	Ambiguous	0.1	2.04	Destabilizing	1.45	Ambiguous	1.28	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.13	Pathogenic	0.05	Affected			2	0	1.0	-34.02
c.1707T>G	F569L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are none; all available predictors that provide a verdict classify the variant as pathogenic, with the exception of FoldX and Foldetta, whose outputs are uncertain and therefore treated as unavailable. The high‑accuracy predictors give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, is uncertain. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000							-9.784	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.677	Likely Pathogenic	0.1977	0.2476		0.86	Ambiguous	0.1	2.04	Destabilizing	1.45	Ambiguous	1.28	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.13	Pathogenic	0.05	Affected			2	0	1.0	-34.02
c.2545G>C	D849H 2D AIThe SynGAP1 missense variant D849H is not 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, and 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; 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		0.712013	Disordered	0.554191	Binding	0.319	0.813	0.500							-4.624	Likely Benign	0.345	Ambiguous	Likely Benign	0.149	Likely Benign	0.1977	0.8673											-0.52	Neutral	0.918	Possibly Damaging	0.697	Possibly Damaging	4.14	Benign	0.00	Affected			1	-1	0.3	22.05
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	0.1977	0.7152											-2.01	Neutral	0.986	Probably Damaging	0.922	Probably Damaging	2.55	Benign	0.21	Tolerated			2	1	0.0	-0.98
c.2222C>T	P741L 2D AIThe SynGAP1 missense variant P741L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875							-4.850	Likely Benign	0.058	Likely Benign	Likely Benign	0.109	Likely Benign	0.1978	0.5780											-0.63	Neutral	0.001	Benign	0.003	Benign	2.84	Benign	0.03	Affected			-3	-3	5.4	16.04
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	0.1978	0.4231											-2.50	Deleterious	0.989	Probably Damaging	0.859	Possibly Damaging	3.67	Benign	0.00	Affected			0	-2	2.9	-59.07
c.2891A>C	H964P 2D AIThe SynGAP1 missense variant H964P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while the only pathogenic call comes from SIFT. ESM1b is uncertain, and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta stability analysis is unavailable. Overall, the collective evidence points to a benign impact for H964P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.990547	Disordered	0.982486	Binding	0.364	0.886	0.750							-7.466	In-Between	0.063	Likely Benign	Likely Benign	0.156	Likely Benign	0.1978	0.4301											-0.34	Neutral	0.000	Benign	0.000	Benign	4.12	Benign	0.04	Affected			0	-2	1.6	-40.02
c.3304G>C	A1102P 2D AIThe SynGAP1 missense variant A1102P is listed in ClinVar (ID 2789225.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.915074	Disordered	0.962659	Binding	0.388	0.859	0.875	Uncertain		1				-5.120	Likely Benign	0.077	Likely Benign	Likely Benign	0.118	Likely Benign	0.1978	0.5919											-0.97	Neutral	0.000	Benign	0.002	Benign	2.26	Pathogenic	0.13	Tolerated	3.77	5	-1	1	-3.4	26.04
c.3983G>T	R1328L 2D AIThe SynGAP1 missense variant R1328L is listed in gnomAD (ID 6‑33451857‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.911775	Binding	0.360	0.762	0.875				6-33451857-G-T			-3.233	Likely Benign	0.452	Ambiguous	Likely Benign	0.038	Likely Benign	0.1978	0.3555											-1.94	Neutral	0.784	Possibly Damaging	0.145	Benign	4.08	Benign	0.01	Affected	3.77	5	-2	-3	8.3	-43.03
c.946A>G	N316D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316D is not 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, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, 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 stability outputs, is uncertain and therefore not considered evidence. Overall, seven of the evaluated tools predict pathogenicity versus four predicting benignity, indicating that the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125							-11.672	Likely Pathogenic	0.777	Likely Pathogenic	Likely Benign	0.293	Likely Benign	0.1978	0.4596		1.18	Ambiguous	0.1	0.46	Likely Benign	0.82	Ambiguous	0.69	Ambiguous	-3.20	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.76	Pathogenic	0.25	Tolerated			2	1	0.0	0.98
c.1442A>C	H481P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H481P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM. Those that predict a pathogenic effect comprise SGM Consensus (Likely Pathogenic), PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and PROVEAN. Tools with inconclusive results are Foldetta (Uncertain) and premPS (Uncertain). High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta remains uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000							-10.205	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	0.385	Likely Benign	0.1979	0.3553		-0.48	Likely Benign	0.3	3.69	Destabilizing	1.61	Ambiguous	0.67	Ambiguous	-5.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.26	Tolerated			0	-2	1.6	-40.02
c.2002T>C	S668P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S668P has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the only benign predictor, while the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify it as pathogenic or likely pathogenic. The premPS score is uncertain and therefore not used as evidence. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports 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 (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.084935	Uncertain	0.922	0.370	0.000							-13.452	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.612	Likely Pathogenic	0.1979	0.5137		6.40	Destabilizing	1.1	10.90	Destabilizing	8.65	Destabilizing	0.61	Ambiguous	-4.82	Deleterious	0.998	Probably Damaging	0.790	Possibly Damaging	3.16	Benign	0.02	Affected			1	-1	-0.8	10.04
c.2626T>C	S876P 2D AIThe SynGAP1 missense variant S876P 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 S876P 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		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250							-5.002	Likely Benign	0.229	Likely Benign	Likely Benign	0.171	Likely Benign	0.1979	0.6928											-2.04	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.56	Benign	0.35	Tolerated			1	-1	-0.8	10.04
c.218G>C	R73T 2D AIThe SynGAP1 missense variant R73T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable and therefore not considered. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods indicates that R73T 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		0.501700	Disordered	0.453164	Uncertain	0.332	0.826	0.375							-4.061	Likely Benign	0.343	Ambiguous	Likely Benign	0.070	Likely Benign	0.1980	0.4439											-1.05	Neutral	0.115	Benign	0.012	Benign	4.05	Benign	0.00	Affected			-1	-1	3.8	-55.08
c.3362G>A	S1121N 2D AIThe SynGAP1 missense variant S1121N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the consensus of the majority of predictors and the high‑accuracy tools points to a benign classification, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875							-6.564	Likely Benign	0.105	Likely Benign	Likely Benign	0.221	Likely Benign	0.1980	0.4211											-0.12	Neutral	0.802	Possibly Damaging	0.266	Benign	5.50	Benign	0.00	Affected			1	1	-2.7	27.03
c.3587A>C	K1196T 2D AIThe SynGAP1 missense variant K1196T is not reported in ClinVar and is absent from 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 and 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 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	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250							-6.611	Likely Benign	0.828	Likely Pathogenic	Ambiguous	0.378	Likely Benign	0.1980	0.2452											-2.17	Neutral	0.980	Probably Damaging	0.862	Possibly Damaging	5.36	Benign	0.04	Affected			0	-1	3.2	-27.07
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	0.1980	0.2695											-3.06	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.15	Pathogenic	0.00	Affected			1	0	-2.2	-14.03
c.706G>C	A236P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A236P missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Foldetta, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas those that predict a pathogenic outcome are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Default; the remaining tools (FoldX, Rosetta, premPS, ESM1b) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of individual tools lean toward pathogenicity, but the two most reliable high‑accuracy methods (AlphaMissense‑Optimized and Foldetta) suggest a benign effect, while the SGM Consensus indicates pathogenicity. Given the mixed evidence, the variant is most likely benign based on the strongest high‑accuracy 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.		PH	0.185198	Structured	0.329926	Uncertain	0.775	0.330	0.000							-7.932	In-Between	0.621	Likely Pathogenic	Likely Benign	0.862	Likely Pathogenic	0.1980	0.4897		-0.99	Ambiguous	0.1	1.44	Ambiguous	0.23	Likely Benign	0.67	Ambiguous	-4.31	Deleterious	0.995	Probably Damaging	0.880	Possibly Damaging	5.78	Benign	0.12	Tolerated			1	-1	-3.4	26.04
c.1849G>A	E617K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E617K is not reported in ClinVar but is present in gnomAD (6‑33440901‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from FoldX, premPS, and SIFT, while pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. A third set of methods (Foldetta, AlphaMissense‑Optimized, Rosetta) yield uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect for E617K, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.155123	Uncertain	0.877	0.240	0.000				6-33440901-G-A	1	6.20e-7	-10.702	Likely Pathogenic	0.910	Likely Pathogenic	Ambiguous	0.534	Likely Pathogenic	0.1981	0.6282		0.37	Likely Benign	0.1	1.19	Ambiguous	0.78	Ambiguous	0.17	Likely Benign	-3.32	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	-1.34	Pathogenic	0.48	Tolerated	3.37	35	1	0	-0.4	-0.94
c.930G>C	E310D 2D 3DClick to see structure in 3D Viewer AISynGAP1 E310D is reported in ClinVar (ID 975473.0) as Pathogenic and is not found in gnomAD. Prediction tools that assess the variant’s effect all converge on a deleterious outcome: REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, leaving no tool in the benign category. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also reports Pathogenic. The single uncertain result from FoldX is treated as unavailable. Overall, the variant is most likely pathogenic, and this assessment is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125	Likely Pathogenic		1				-11.218	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.666	Likely Pathogenic	0.1981	0.5222		1.87	Ambiguous	0.5	2.39	Destabilizing	2.13	Destabilizing	1.04	Destabilizing	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.19	Pathogenic	0.02	Affected	3.38	19	3	2	0.0	-14.03	232.6	27.2	0.1	0.0	0.1	0.1						X		Potentially Benign	The carboxylate group of Glu310, located in an anti-parallel β sheet strand (res. Thr305-Asn315), is ideally positioned to interact with the hydroxyl and backbone amide groups of Thr295 on a twisted anti-parallel β strand. Because the carboxylate group can also interact with the GAP domain residues (e.g., Gln612, Tyr614), Glu310 potentially plays a key role in maintaining the tertiary assembly between the C2 and GAP domains. In the variant simulations, the carboxylate group of Asp310 can form the same interactions as glutamate; however, due to its one hydrocarbon shorter length, the connections are less stable or less optimal.
c.930G>T	E310D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E310D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity uniformly favor a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL (Pathogenic), Rosetta (Pathogenic), Foldetta (Pathogenic), premPS (Pathogenic), PROVEAN (Pathogenic), polyPhen‑2 HumDiv (Pathogenic), polyPhen‑2 HumVar (Pathogenic), SIFT (Pathogenic), ESM1b (Pathogenic), FATHMM (Pathogenic), AlphaMissense‑Default (Pathogenic), and AlphaMissense‑Optimized (Pathogenic). No tool predicts a benign outcome; the only inconclusive result is FoldX (Uncertain). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status, which currently has no entry for E310D. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125							-11.218	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.666	Likely Pathogenic	0.1981	0.5222		1.87	Ambiguous	0.5	2.39	Destabilizing	2.13	Destabilizing	1.04	Destabilizing	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.19	Pathogenic	0.02	Affected	3.38	19	3	2	0.0	-14.03	232.6	27.2	0.1	0.0	0.1	0.1						X		Potentially Benign	The carboxylate group of Glu310, located in an anti-parallel β sheet strand (res. Thr305-Asn315), is ideally positioned to interact with the hydroxyl and backbone amide groups of Thr295 on a twisted anti-parallel β strand. Because the carboxylate group can also interact with the GAP domain residues (e.g., Gln612, Tyr614), Glu310 potentially plays a key role in maintaining the tertiary assembly between the C2 and GAP domains. In the variant simulations, the carboxylate group of Asp310 can form the same interactions as glutamate; however, due to its one hydrocarbon shorter length, the connections are less stable or less optimal.
c.1028T>G	V343G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the preponderance of evidence indicates that V343G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250							-11.332	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	0.421	Likely Benign	0.1982	0.3341		2.49	Destabilizing	0.1	4.40	Destabilizing	3.45	Destabilizing	1.68	Destabilizing	-5.84	Deleterious	0.898	Possibly Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.00	Affected			-1	-3	-4.6	-42.08
c.3128G>T	R1043M 2D AIThe SynGAP1 missense variant R1043M is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign, while polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for R1043M, 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		0.978672	Disordered	0.954069	Binding	0.299	0.853	0.625							-4.800	Likely Benign	0.510	Ambiguous	Likely Benign	0.471	Likely Benign	0.1982	0.4468											-1.98	Neutral	0.744	Possibly Damaging	0.229	Benign	5.38	Benign	0.00	Affected			0	-1	6.4	-24.99
c.1102C>A	P368T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P368T missense variant is not listed in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. FoldX, Rosetta, and Foldetta report uncertain or inconclusive stability changes 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 a tie (2 benign, 2 pathogenic) and thus inconclusive, and Foldetta remains uncertain. Overall, the predictions are evenly split between benign and pathogenic, providing no definitive classification. The variant’s status does not contradict ClinVar, which has no entry for it. 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							-5.308	Likely Benign	0.284	Likely Benign	Likely Benign	0.188	Likely Benign	0.1983	0.6155		1.95	Ambiguous	0.6	1.61	Ambiguous	1.78	Ambiguous	0.45	Likely Benign	-5.43	Deleterious	0.941	Possibly Damaging	0.527	Possibly Damaging	1.72	Pathogenic	0.01	Affected			0	-1	0.9	3.99
c.1489T>C	Y497H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497H is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a destabilizing, pathogenic effect. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.393608	Uncertain	0.950	0.181	0.000							-10.970	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.819	Likely Pathogenic	0.1983	0.0612		2.46	Destabilizing	0.1	2.40	Destabilizing	2.43	Destabilizing	1.29	Destabilizing	-4.94	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.65	Pathogenic	0.02	Affected			0	2	-1.9	-26.03
c.3409C>A	H1137N 2D AIThe SynGAP1 missense variant H1137N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.756488	Binding	0.314	0.879	0.875							-3.105	Likely Benign	0.063	Likely Benign	Likely Benign	0.208	Likely Benign	0.1983	0.3638											-1.53	Neutral	0.625	Possibly Damaging	0.353	Benign	5.34	Benign	0.00	Affected			2	1	-0.3	-23.04
c.2308C>A	Q770K 2D AIThe SynGAP1 missense variant Q770K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, 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, 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		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250							-4.768	Likely Benign	0.367	Ambiguous	Likely Benign	0.106	Likely Benign	0.1984	0.4737											-0.72	Neutral	0.002	Benign	0.003	Benign	4.20	Benign	0.14	Tolerated			1	1	-0.4	0.04
c.3197C>A	P1066H 2D AIThe SynGAP1 missense variant P1066H 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 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, 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		0.967676	Disordered	0.968838	Binding	0.403	0.913	0.875							-6.034	Likely Benign	0.185	Likely Benign	Likely Benign	0.146	Likely Benign	0.1984	0.5861											-2.90	Deleterious	1.000	Probably Damaging	0.975	Probably Damaging	2.61	Benign	0.00	Affected			0	-2	-1.6	40.02
c.47T>A	M16K 2D AIThe SynGAP1 missense variant M16K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational predictions and the high‑accuracy consensus suggest that M16K is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375							-2.567	Likely Benign	0.635	Likely Pathogenic	Likely Benign	0.185	Likely Benign	0.1984	0.1112											-0.37	Neutral	0.003	Benign	0.001	Benign	4.23	Benign	0.00	Affected			0	-1	-5.8	-3.02
c.85A>C	M29L 2D AIThe SynGAP1 missense variant M29L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250							-1.633	Likely Benign	0.079	Likely Benign	Likely Benign	0.200	Likely Benign	0.1984	0.5336											-0.49	Neutral	0.006	Benign	0.039	Benign	4.27	Benign	0.00	Affected			4	2	1.9	-18.03
c.85A>T	M29L 2D AIThe SynGAP1 missense variant M29L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250							-1.633	Likely Benign	0.079	Likely Benign	Likely Benign	0.200	Likely Benign	0.1984	0.5336											-0.49	Neutral	0.006	Benign	0.039	Benign	4.27	Benign	0.00	Affected			4	2	1.9	-18.03
c.1222A>C	T408P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T408P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX, premPS, and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie and thus unavailable; Foldetta remains uncertain. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000							-10.384	Likely Pathogenic	0.230	Likely Benign	Likely Benign	0.323	Likely Benign	0.1985	0.5779		1.08	Ambiguous	0.3	2.27	Destabilizing	1.68	Ambiguous	0.73	Ambiguous	-4.19	Deleterious	0.998	Probably Damaging	0.963	Probably Damaging	4.07	Benign	0.05	Affected			0	-1	-0.9	-3.99
c.1681T>G	F561V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. All available evidence points to a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000							-11.371	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.827	Likely Pathogenic	0.1985	0.1575		3.11	Destabilizing	0.1	2.58	Destabilizing	2.85	Destabilizing	1.48	Destabilizing	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.04	Affected			-1	-1	1.4	-48.04
c.2656G>C	A886P 2D AIThe SynGAP1 missense variant A886P is 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 unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) support a benign classification. This consensus does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.619166	Binding	0.359	0.922	0.500							-1.931	Likely Benign	0.091	Likely Benign	Likely Benign	0.073	Likely Benign	0.1985	0.4773											-1.20	Neutral	0.812	Possibly Damaging	0.575	Possibly Damaging	2.15	Pathogenic	0.00	Affected			1	-1	-3.4	26.04
c.1082A>C	Q361P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361P is listed in ClinVar as Pathogenic (ClinVar ID 3235087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and premPS. All other evaluated algorithms—FoldX, Rosetta, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy methods specifically give a pathogenic verdict: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Based on the overwhelming agreement of these predictions, the variant is most likely pathogenic, which is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250	Likely Pathogenic		1				-13.280	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.482	Likely Benign	0.1986	0.5151		3.12	Destabilizing	0.0	3.45	Destabilizing	3.29	Destabilizing	0.38	Likely Benign	-3.03	Deleterious	0.996	Probably Damaging	0.979	Probably Damaging	1.63	Pathogenic	0.05	Affected	3.37	25	-1	0	1.9	-31.01
c.291G>C	E97D 2D AIThe SynGAP1 missense variant E97D 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 evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.609018	Binding	0.340	0.867	0.625							-3.239	Likely Benign	0.077	Likely Benign	Likely Benign	0.081	Likely Benign	0.1987	0.5559											-0.49	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	4.12	Benign	0.00	Affected	4.32	1	3	2	0.0	-14.03
c.291G>T	E97D 2D AIThe SynGAP1 missense variant E97D is listed in ClinVar (ID 1313570.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33425899‑G‑T). 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 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 consensus does not contradict the ClinVar “Uncertain” status, which remains unresolved. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.609018	Binding	0.340	0.867	0.625	Uncertain		3	6-33425899-G-T			-3.239	Likely Benign	0.077	Likely Benign	Likely Benign	0.081	Likely Benign	0.1987	0.5559											-0.49	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	4.12	Benign	0.00	Affected	4.32	1	3	2	0.0	-14.03
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	0.1987	0.1614											-1.99	Neutral	0.987	Probably Damaging	0.968	Probably Damaging	5.54	Benign	0.02	Affected			-1	-1	-2.6	-30.09
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	0.276	Likely Benign	0.1988	0.3317		1.46	Ambiguous	0.1	2.06	Destabilizing	1.76	Ambiguous	0.83	Ambiguous	-3.79	Deleterious	0.991	Probably Damaging	0.628	Possibly Damaging	3.32	Benign	0.00	Affected			1	0	-2.2	-14.03
c.1690G>A	E564K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564K is not reported in ClinVar and is present in the gnomAD database (variant ID 6‑33440742‑G‑A). Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while only SIFT predicts a benign outcome. Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence supports a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023534	Structured	0.038418	Uncertain	0.891	0.208	0.000				6-33440742-G-A			-15.834	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.854	Likely Pathogenic	0.1988	0.5280		0.76	Ambiguous	0.1	2.06	Destabilizing	1.41	Ambiguous	0.89	Ambiguous	-3.95	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	-1.35	Pathogenic	0.10	Tolerated	3.37	35	1	0	-0.4	-0.94
c.2014A>C	T672P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T672P missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain results come from premPS and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. No predictions are missing or inconclusive. Overall, the majority of evidence points to a pathogenic impact for T672P. This conclusion is not contradicted by ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000							-11.022	Likely Pathogenic	0.346	Ambiguous	Likely Benign	0.087	Likely Benign	0.1988	0.5532		2.22	Destabilizing	0.2	5.54	Destabilizing	3.88	Destabilizing	0.55	Ambiguous	-4.20	Deleterious	0.968	Probably Damaging	0.824	Possibly Damaging	3.40	Benign	0.01	Affected			0	-1	-0.9	-3.99
c.2890C>A	H964N 2D AIThe SynGAP1 missense variant H964N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta 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		0.990547	Disordered	0.982486	Binding	0.364	0.886	0.750							-8.073	Likely Pathogenic	0.084	Likely Benign	Likely Benign	0.098	Likely Benign	0.1988	0.3495											-0.30	Neutral	0.000	Benign	0.000	Benign	4.18	Benign	0.64	Tolerated			2	1	-0.3	-23.04
c.3254G>C	R1085P 2D AIThe SynGAP1 missense variant R1085P is not 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 vs 2). Foldetta results are unavailable. Overall, the majority of standard predictors (five pathogenic vs. four benign) lean toward a pathogenic interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction and the inconclusive SGM Consensus temper this view. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000							-2.527	Likely Benign	0.759	Likely Pathogenic	Likely Benign	0.260	Likely Benign	0.1988	0.4524											-2.55	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.71	Benign	0.01	Affected			0	-2	2.9	-59.07
c.3967C>A	P1323T 2D AIThe SynGAP1 missense variant P1323T is reported in gnomAD (ID 6‑33451841‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. Only two algorithms—polyPhen‑2 HumDiv and SIFT—suggest a damaging impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with any ClinVar classification, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875				6-33451841-C-A			-6.296	Likely Benign	0.073	Likely Benign	Likely Benign	0.064	Likely Benign	0.1988	0.5161											-0.37	Neutral	0.588	Possibly Damaging	0.227	Benign	3.95	Benign	0.00	Affected	4.32	1	-1	0	0.9	3.99
c.2491G>A	E831K 2D AIThe SynGAP1 missense variant E831K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, FATHMM, and AlphaMissense‑Default; ESM1b is uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools lean benign, but the high‑accuracy consensus and several individual pathogenic predictions suggest a pathogenic likelihood. Thus, the variant is most likely pathogenic based on the available 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.			0.626927	Disordered	0.617732	Binding	0.319	0.874	0.375							-7.447	In-Between	0.636	Likely Pathogenic	Likely Benign	0.167	Likely Benign	0.1989	0.6995											-1.43	Neutral	0.625	Possibly Damaging	0.252	Benign	2.37	Pathogenic	0.07	Tolerated			0	1	-0.4	-0.94
c.3046G>A	D1016N 2D AIThe SynGAP1 missense variant D1016N 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, 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 assessments therefore indicate a benign prediction: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and no Foldetta data is available. 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		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625							-3.674	Likely Benign	0.460	Ambiguous	Likely Benign	0.123	Likely Benign	0.1989	0.7529											-2.12	Neutral	0.856	Possibly Damaging	0.723	Possibly Damaging	2.50	Benign	0.01	Affected			2	1	0.0	-0.98
c.3999G>C	E1333D 2D AIThe SynGAP1 missense variant E1333D is not reported in ClinVar (no ClinVar ID) 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 E1333D, 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		0.930790	Disordered	0.953319	Binding	0.347	0.746	0.750							-4.239	Likely Benign	0.651	Likely Pathogenic	Likely Benign	0.117	Likely Benign	0.1989	0.5029											-1.78	Neutral	0.953	Possibly Damaging	0.935	Probably Damaging	2.88	Benign	0.00	Affected			3	2	0.0	-14.03
c.3999G>T	E1333D 2D AIThe SynGAP1 missense variant E1333D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT classify the change as pathogenic, and AlphaMissense‑Default also predicts pathogenicity. High‑accuracy tools specifically give a benign prediction for AlphaMissense‑Optimized and a likely benign result for the SGM‑Consensus; Foldetta data are unavailable. Overall, the majority of evidence supports a benign interpretation, and this is consistent with the absence of a ClinVar pathogenic claim. Thus, the variant is most likely benign, and this is consistent with the lack of a ClinVar pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.953319	Binding	0.347	0.746	0.750							-4.239	Likely Benign	0.651	Likely Pathogenic	Likely Benign	0.117	Likely Benign	0.1989	0.5029											-1.78	Neutral	0.953	Possibly Damaging	0.935	Probably Damaging	2.88	Benign	0.00	Affected			3	2	0.0	-14.03
c.1642G>A	E548K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548K missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicting likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicating a benign effect on protein stability. Overall, the balance of evidence leans toward a pathogenic interpretation, with no conflict with ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000							-13.734	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.348	Likely Benign	0.1990	0.4491		-0.34	Likely Benign	0.0	-0.19	Likely Benign	-0.27	Likely Benign	0.13	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	3.33	Benign	0.09	Tolerated			0	1	-0.4	-0.94
c.1853A>C	Q618P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q618P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are SGM Consensus, ESM1b, FATHMM, PROVEAN, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as uncertain. Overall, the majority of predictions lean toward a benign effect, though a subset of high‑confidence tools suggest pathogenicity. The variant’s status is not contradicted by ClinVar, which has no entry for this change. Based on the collective evidence, Q618P is most likely benign, albeit with some conflicting pathogenic signals from high‑accuracy predictors. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.138725	Uncertain	0.904	0.240	0.000							-8.273	Likely Pathogenic	0.248	Likely Benign	Likely Benign	0.449	Likely Benign	0.1990	0.4011		-0.11	Likely Benign	0.1	3.41	Destabilizing	1.65	Ambiguous	0.23	Likely Benign	-3.32	Deleterious	0.261	Benign	0.246	Benign	-1.35	Pathogenic	0.08	Tolerated			0	-1	1.9	-31.01
c.1948A>C	N650H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N650H lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, FoldX, and the SGM‑Consensus (majority vote). Uncertain or inconclusive results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.361944	Uncertain	0.961	0.357	0.000							-14.187	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.465	Likely Benign	0.1990	0.4784		2.14	Destabilizing	0.3	1.79	Ambiguous	1.97	Ambiguous	0.55	Ambiguous	-4.98	Deleterious	0.999	Probably Damaging	0.929	Probably Damaging	3.01	Benign	0.05	Affected			2	1	0.3	23.04
c.2909A>T	E970V 2D AIThe SynGAP1 missense variant E970V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign interpretation, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.951925	Disordered	0.953422	Binding	0.342	0.902	0.750							-2.791	Likely Benign	0.208	Likely Benign	Likely Benign	0.245	Likely Benign	0.1990	0.7037											-1.08	Neutral	0.002	Benign	0.002	Benign	4.11	Benign	0.08	Tolerated			-2	-2	7.7	-29.98
c.2785A>G	N929D 2D AIThe SynGAP1 missense variant N929D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which reports “Likely Pathogenic”). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenicity. Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375							-6.856	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic	0.365	Likely Benign	0.1991	0.4605											-3.86	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.49	Pathogenic	0.00	Affected			2	1	0.0	0.98
c.676T>A	S226T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S226T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while FoldX is uncertain and therefore treated as unavailable. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.129801	Structured	0.334959	Uncertain	0.800	0.324	0.250							-5.066	Likely Benign	0.102	Likely Benign	Likely Benign	0.326	Likely Benign	0.1991	0.6681		0.53	Ambiguous	0.2	0.12	Likely Benign	0.33	Likely Benign	-0.10	Likely Benign	-1.47	Neutral	0.390	Benign	0.079	Benign	5.75	Benign	0.05	Affected			1	1	0.1	14.03
c.47T>G	M16R 2D AIThe SynGAP1 missense variant M16R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus also indicates likely benign, and no Foldetta stability data are available. Taken together, the preponderance of evidence supports a benign classification for M16R, 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		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375							-1.475	Likely Benign	0.485	Ambiguous	Likely Benign	0.191	Likely Benign	0.1992	0.1093											-0.25	Neutral	0.014	Benign	0.003	Benign	4.21	Benign	0.00	Affected			0	-1	-6.4	24.99
c.112C>A	P38T 2D AIThe SynGAP1 missense variant P38T 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		0.497853	Structured	0.433285	Uncertain	0.344	0.791	0.375							-3.248	Likely Benign	0.116	Likely Benign	Likely Benign	0.114	Likely Benign	0.1993	0.6717											-1.91	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.06	Benign	0.00	Affected			0	-1	0.9	3.99
c.1436G>C	R479P 2D 3DClick to see structure in 3D Viewer AIClinVar lists the SynGAP1 R479P variant as Uncertain, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Those that predict a pathogenic effect are FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are AlphaMissense‑Optimized and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as pathogenic. Overall, the majority of tools and the high‑accuracy methods support a pathogenic classification, which is in contrast to the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000	Uncertain		1				-11.795	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.277	Likely Benign	0.1993	0.3747		2.86	Destabilizing	0.2	3.88	Destabilizing	3.37	Destabilizing	0.81	Ambiguous	-3.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.41	Benign	0.18	Tolerated			0	-2	2.9	-59.07
c.2138C>T	P713L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000							-11.323	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous	0.324	Likely Benign	0.1993	0.5261		0.18	Likely Benign	0.1	-0.03	Likely Benign	0.08	Likely Benign	0.55	Ambiguous	-8.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.34	Benign	0.00	Affected			-3	-3	5.4	16.04
c.2183C>A	P728H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which predict a deleterious impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic effect for P728H, and this conclusion does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625							-8.897	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.402	Likely Benign	0.1993	0.3016		0.94	Ambiguous	0.0	0.86	Ambiguous	0.90	Ambiguous	0.64	Ambiguous	-7.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.65	Pathogenic	0.00	Affected			0	-2	-1.6	40.02
c.2354G>T	R785L 2D AIThe SynGAP1 missense variant R785L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625							-4.457	Likely Benign	0.699	Likely Pathogenic	Likely Benign	0.158	Likely Benign	0.1993	0.4539											-4.43	Deleterious	0.960	Probably Damaging	0.627	Possibly Damaging	2.26	Pathogenic	0.01	Affected			-3	-2	8.3	-43.03
c.2405G>A	G802D 2D AIThe SynGAP1 missense variant G802D is listed in ClinVar with an “Uncertain” status and is present in gnomAD (6‑33442957‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all classifying the change as benign. No tool predicts a pathogenic outcome. The high‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625	Uncertain		1	6-33442957-G-A	1	6.20e-7	-5.083	Likely Benign	0.476	Ambiguous	Likely Benign	0.153	Likely Benign	0.1993	0.2742											-0.38	Neutral	0.126	Benign	0.138	Benign	2.72	Benign	0.09	Tolerated	3.77	5	1	-1	-3.1	58.04
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	0.798	Likely Pathogenic	0.1994	0.1677		2.07	Destabilizing	0.1	2.22	Destabilizing	2.15	Destabilizing	1.07	Destabilizing	-6.35	Deleterious	0.984	Probably Damaging	1.000	Probably Damaging	-1.39	Pathogenic	0.01	Affected			-1	-3	-4.6	-42.08
c.3268A>G	N1090D 2D AIThe SynGAP1 missense variant N1090D is not 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		0.896620	Disordered	0.979886	Binding	0.341	0.887	1.000							-3.354	Likely Benign	0.827	Likely Pathogenic	Ambiguous	0.066	Likely Benign	0.1994	0.4375											-1.39	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.70	Benign	0.47	Tolerated			2	1	0.0	0.98
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	0.1995	0.3705											-1.95	Neutral	0.992	Probably Damaging	0.977	Probably Damaging	4.16	Benign	0.00	Affected			0	-2	-1.6	40.02
c.1264G>A	E422K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422K missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus also indicates Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the balance of evidence leans toward pathogenicity, and this assessment does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000							-13.042	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.346	Likely Benign	0.1995	0.5129		0.30	Likely Benign	0.0	0.10	Likely Benign	0.20	Likely Benign	0.32	Likely Benign	-3.52	Deleterious	0.998	Probably Damaging	0.975	Probably Damaging	3.39	Benign	0.04	Affected			0	1	-0.4	-0.94
c.187G>A	E63K 2D AIThe SynGAP1 E63K missense variant (ClinVar ID 2830630.0) is listed as “Uncertain” and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default all predict a pathogenic outcome. AlphaMissense‑Optimized is inconclusive, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. Overall, the high‑accuracy consensus leans toward a benign effect, and this assessment does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.474807	Uncertain	0.494	0.739	0.125	Uncertain		1				-4.976	Likely Benign	0.894	Likely Pathogenic	Ambiguous	0.103	Likely Benign	0.1995	0.7261											-0.70	Neutral	0.458	Possibly Damaging	0.678	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	1	0	-0.4	-0.94
c.4008G>C	E1336D 2D AIThe SynGAP1 missense variant E1336D is listed in ClinVar (ID 3323942.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus result is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, consistent with the ClinVar benign designation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750	Likely Benign		1				-3.344	Likely Benign	0.596	Likely Pathogenic	Likely Benign	0.062	Likely Benign	0.1995	0.5101											-1.92	Neutral	0.001	Benign	0.003	Benign	3.30	Benign	0.00	Affected	3.77	5	2	3	0.0	-14.03
c.4008G>T	E1336D 2D AIThe SynGAP1 missense variant E1336D is catalogued in gnomAD (ID 6‑33451882‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign or likely benign outcome. Only two tools—SIFT and AlphaMissense‑Default—predict pathogenicity. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also reports it as likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign classification, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750				6-33451882-G-T			-3.344	Likely Benign	0.596	Likely Pathogenic	Likely Benign	0.065	Likely Benign	0.1995	0.5101											-1.92	Neutral	0.001	Benign	0.003	Benign	3.30	Benign	0.00	Affected	3.77	5	2	3	0.0	-14.03
c.3833C>A	P1278H 2D AIThe SynGAP1 missense variant P1278H is reported in gnomAD (variant ID 6‑33447881‑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 predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. High‑accuracy assessments confirm the benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the same set of benign predictions) is benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.806955	Binding	0.532	0.722	0.750				6-33447881-C-A	7	4.51e-6	-5.691	Likely Benign	0.142	Likely Benign	Likely Benign	0.087	Likely Benign	0.1997	0.3155											-1.69	Neutral	0.938	Possibly Damaging	0.477	Possibly Damaging	2.67	Benign	0.01	Affected	3.77	5	-2	0	-1.6	40.02
c.934T>A	F312I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312I is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000							-12.000	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.872	Likely Pathogenic	0.1997	0.2842		2.09	Destabilizing	0.3	3.10	Destabilizing	2.60	Destabilizing	1.72	Destabilizing	-5.52	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.23	Pathogenic	0.01	Affected			1	0	1.7	-34.02
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	0.474	Likely Benign	0.1998	0.4000		0.67	Ambiguous	0.3	0.48	Likely Benign	0.58	Ambiguous	0.13	Likely Benign	-2.79	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.15	Tolerated			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	0.474	Likely Benign	0.1998	0.4000		0.67	Ambiguous	0.3	0.48	Likely Benign	0.58	Ambiguous	0.13	Likely Benign	-2.79	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	-1.27	Pathogenic	0.15	Tolerated			3	2	0.0	-14.03
c.2191C>A	Q731K 2D AIThe SynGAP1 missense variant Q731K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The 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, did not provide a result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools 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		0.750527	Disordered	0.415202	Uncertain	0.507	0.654	0.750							-6.686	Likely Benign	0.349	Ambiguous	Likely Benign	0.066	Likely Benign	0.1998	0.3932											-1.58	Neutral	0.490	Possibly Damaging	0.149	Benign	2.67	Benign	0.20	Tolerated			1	1	-0.4	0.04
c.2282G>C	R761P 2D AIThe SynGAP1 missense variant R761P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441747‑G‑C). 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 the 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, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions point to a benign impact, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. 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	Uncertain		3	6-33441747-G-C	1	6.20e-7	-5.091	Likely Benign	0.640	Likely Pathogenic	Likely Benign	0.201	Likely Benign	0.1998	0.4449											-1.89	Neutral	0.999	Probably Damaging	0.968	Probably Damaging	2.69	Benign	0.38	Tolerated	3.99	5	0	-2	2.9	-59.07
c.3656A>T	Y1219F 2D AIThe SynGAP1 missense variant Y1219F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, while AlphaMissense‑Optimized remains uncertain. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a pathogenic effect for Y1219F, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375							-7.202	In-Between	0.837	Likely Pathogenic	Ambiguous	0.272	Likely Benign	0.1998	0.2583											-2.79	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.23	Pathogenic	0.00	Affected			7	3	4.1	-16.00
c.3755A>C	Q1252P 2D AIThe SynGAP1 missense variant Q1252P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875							-14.386	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.352	Likely Benign	0.1998	0.3742											-4.75	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.95	Pathogenic	0.00	Affected			0	-1	1.9	-31.01
c.385T>C	S129P 2D AIThe SynGAP1 missense variant S129P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, 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		0.517562	Disordered	0.713635	Binding	0.311	0.880	0.625							-2.469	Likely Benign	0.237	Likely Benign	Likely Benign	0.220	Likely Benign	0.1998	0.4989											-0.09	Neutral	0.454	Possibly Damaging	0.133	Benign	4.11	Benign	0.32	Tolerated			1	-1	-0.8	10.04
c.934T>G	F312V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312V is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the change as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000							-12.206	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.877	Likely Pathogenic	0.1998	0.2810		2.13	Destabilizing	0.1	3.46	Destabilizing	2.80	Destabilizing	1.80	Destabilizing	-6.43	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.25	Pathogenic	0.00	Affected			-1	-1	1.4	-48.04
c.173T>C	M58T 2D AIThe SynGAP1 missense variant M58T is listed in gnomAD (ID 6‑33423582‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000				6-33423582-T-C	1	6.20e-7	-4.308	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic	0.159	Likely Benign	0.1999	0.2357											-1.58	Neutral	0.018	Benign	0.184	Benign	4.09	Benign	0.00	Affected	4.32	1	-1	-1	-2.6	-30.09
c.1892A>C	Q631P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q631P is not reported in ClinVar and has no entry in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining eleven tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the change as pathogenic. The high‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also indicates pathogenic. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.038963	Uncertain	0.948	0.230	0.000							-16.914	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.641	Likely Pathogenic	0.1999	0.2982		4.98	Destabilizing	0.3	11.18	Destabilizing	8.08	Destabilizing	0.56	Ambiguous	-5.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.75	Benign	0.00	Affected			0	-1	1.9	-31.01
c.41C>A	P14H 2D AIThe SynGAP1 missense variant P14H is listed in gnomAD (ID 6‑33420305‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its status is unavailable. Overall, the majority of predictions—including the high‑accuracy tools—indicate that P14H 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		0.433034	Structured	0.471596	Uncertain	0.399	0.909	0.375				6-33420305-C-A			-3.747	Likely Benign	0.231	Likely Benign	Likely Benign	0.171	Likely Benign	0.1999	0.5176											-0.27	Neutral	0.742	Possibly Damaging	0.091	Benign	4.15	Benign	0.00	Affected	4.32	1	-2	0	-1.6	40.02
c.1039A>C	T347P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T347P variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and FATHMM. Three tools (FoldX, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. 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.		C2	0.268042	Structured	0.349915	Uncertain	0.951	0.434	0.000							-9.323	Likely Pathogenic	0.417	Ambiguous	Likely Benign	0.236	Likely Benign	0.2000	0.5350		0.55	Ambiguous	0.0	0.28	Likely Benign	0.42	Likely Benign	0.65	Ambiguous	-2.41	Neutral	0.627	Possibly Damaging	0.139	Benign	1.63	Pathogenic	0.12	Tolerated			0	-1	-0.9	-3.99
c.273G>C	E91D 2D AIThe SynGAP1 missense variant E91D is reported in gnomAD (variant ID 6‑33425881‑G‑C) 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 reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, 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		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500				6-33425881-G-C	1	6.20e-7	-3.160	Likely Benign	0.293	Likely Benign	Likely Benign	0.095	Likely Benign	0.2000	0.5219											-0.84	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	2	3	0.0	-14.03
c.273G>T	E91D 2D AIThe SynGAP1 missense variant E91D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to 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.	Likely Benign		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500							-3.160	Likely Benign	0.293	Likely Benign	Likely Benign	0.095	Likely Benign	0.2000	0.5219											-0.84	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.98	Benign	0.00	Affected	4.32	1	2	3	0.0	-14.03
c.2171C>G	A724G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250							-8.908	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	0.286	Likely Benign	0.2001	0.3609		1.45	Ambiguous	0.1	1.73	Ambiguous	1.59	Ambiguous	0.56	Ambiguous	-3.10	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.07	Pathogenic	0.08	Tolerated			1	0	-2.2	-14.03
c.2750C>T	P917L 2D AIThe SynGAP1 missense variant P917L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.863949	Binding	0.314	0.862	0.375							-3.369	Likely Benign	0.172	Likely Benign	Likely Benign	0.075	Likely Benign	0.2001	0.6351											-2.35	Neutral	0.425	Benign	0.233	Benign	2.75	Benign	0.00	Affected			-3	-3	5.4	16.04
c.3400A>C	T1134P 2D AIThe SynGAP1 missense variant T1134P is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.813034	Binding	0.335	0.885	0.875							-2.993	Likely Benign	0.098	Likely Benign	Likely Benign	0.164	Likely Benign	0.2001	0.5165											-0.57	Neutral	0.013	Benign	0.022	Benign	5.41	Benign	0.07	Tolerated			0	-1	-0.9	-3.99
c.1289T>C	M430T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M430T is reported in gnomAD (6‑33438194‑T‑C) and has no ClinVar entry. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, FoldX (uncertain), Rosetta, Foldetta (uncertain), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as benign or likely benign. No tool predicts pathogenicity. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign, the SGM Consensus is likely benign, and Foldetta is uncertain. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Thus, the variant is most likely benign, and this is not contradictory to ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.385298	Uncertain	0.952	0.306	0.000				6-33438194-T-C	1	6.19e-7	-3.430	Likely Benign	0.107	Likely Benign	Likely Benign	0.103	Likely Benign	0.2002	0.3184		1.89	Ambiguous	0.1	0.01	Likely Benign	0.95	Ambiguous	0.43	Likely Benign	-1.48	Neutral	0.016	Benign	0.010	Benign	3.48	Benign	0.40	Tolerated	3.37	29	-1	-1	-2.6	-30.09
c.2181C>A	N727K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N727K is catalogued in gnomAD (ID 6‑33441646‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, SIFT, and the protein‑folding stability method Foldetta; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the consensus score SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM Consensus indicates likely pathogenic, and Foldetta reports benign stability. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625				6-33441646-C-A	1	6.19e-7	-10.601	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.148	Likely Benign	0.2002	0.5590		-0.12	Likely Benign	0.2	-0.44	Likely Benign	-0.28	Likely Benign	0.86	Ambiguous	-3.82	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.12	Tolerated	3.59	7	0	1	-0.4	14.07
c.2181C>G	N727K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727K is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence (seven pathogenic vs. five benign, with two uncertain) points to a pathogenic impact. This conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625							-10.601	Likely Pathogenic	0.884	Likely Pathogenic	Ambiguous	0.148	Likely Benign	0.2002	0.5590		-0.12	Likely Benign	0.2	-0.44	Likely Benign	-0.28	Likely Benign	0.86	Ambiguous	-3.82	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.12	Tolerated	3.59	7	0	1	-0.4	14.07
c.3662G>C	R1221P 2D AIThe SynGAP1 missense variant R1221P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and the high‑accuracy tools points to a pathogenic effect for R1221P. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375							-14.148	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.170	Likely Benign	0.2002	0.3095											-3.50	Deleterious	0.999	Probably Damaging	0.968	Probably Damaging	2.52	Benign	0.05	Affected			0	-2	2.9	-59.07
c.1348G>T	A450S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A450S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining methods—FoldX, Rosetta, Foldetta, and premPS—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus unavailable; Foldetta is uncertain. Overall, the balance of evidence (five benign versus four pathogenic predictions, with three uncertain) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.321458	Structured	0.306281	Uncertain	0.963	0.234	0.000							-9.257	Likely Pathogenic	0.274	Likely Benign	Likely Benign	0.268	Likely Benign	0.2003	0.4322		0.81	Ambiguous	0.0	1.35	Ambiguous	1.08	Ambiguous	0.69	Ambiguous	-2.70	Deleterious	0.965	Probably Damaging	0.972	Probably Damaging	3.47	Benign	0.10	Tolerated			1	1	-2.6	16.00
c.292C>A	H98N 2D AIThe SynGAP1 missense variant H98N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: 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 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		0.733139	Disordered	0.631713	Binding	0.348	0.872	0.625							-3.855	Likely Benign	0.070	Likely Benign	Likely Benign	0.103	Likely Benign	0.2003	0.3759											-0.35	Neutral	0.115	Benign	0.012	Benign	4.24	Benign	0.00	Affected			2	1	-0.3	-23.04
c.3041G>A	G1014D 2D AIThe SynGAP1 missense variant G1014D is catalogued in gnomAD (6‑33443593‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign impact for G1014D, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.914808	Binding	0.293	0.835	0.625				6-33443593-G-A			-4.462	Likely Benign	0.543	Ambiguous	Likely Benign	0.029	Likely Benign	0.2003	0.2942											-1.39	Neutral	0.818	Possibly Damaging	0.381	Benign	2.74	Benign	0.77	Tolerated	3.77	5	-1	1	-3.1	58.04
c.3757G>T	A1253S 2D AIThe SynGAP1 missense variant A1253S is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta results are unavailable. Based on the consensus of all available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.661982	Disordered	0.391377	Uncertain	0.881	0.550	0.750							-3.639	Likely Benign	0.090	Likely Benign	Likely Benign	0.041	Likely Benign	0.2003	0.4159											0.05	Neutral	0.081	Benign	0.111	Benign	2.81	Benign	0.33	Tolerated			1	1	-2.6	16.00
c.2800A>C	M934L 2D AIThe SynGAP1 missense variant M934L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions points to a benign impact, and this is consistent with the lack of a ClinVar classification—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625							-2.482	Likely Benign	0.079	Likely Benign	Likely Benign	0.093	Likely Benign	0.2004	0.4051											-0.73	Neutral	0.002	Benign	0.002	Benign	3.03	Benign	0.68	Tolerated			4	2	1.9	-18.03
c.2800A>T	M934L 2D AIThe SynGAP1 missense variant M934L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Consequently, the variant is most likely benign based on the collective predictions, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.984677	Binding	0.290	0.867	0.625							-2.482	Likely Benign	0.079	Likely Benign	Likely Benign	0.093	Likely Benign	0.2004	0.4051											-0.73	Neutral	0.002	Benign	0.002	Benign	3.03	Benign	0.68	Tolerated			4	2	1.9	-18.03
c.503A>C	H168P 2D AIThe SynGAP1 missense variant H168P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Taken together, the preponderance of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.502450	Binding	0.402	0.678	0.125							-7.686	In-Between	0.124	Likely Benign	Likely Benign	0.279	Likely Benign	0.2004	0.3960											-1.66	Neutral	0.072	Benign	0.043	Benign	4.19	Benign	0.02	Affected			0	-2	1.6	-40.02
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	0.2005	0.3539											-1.36	Neutral	0.992	Probably Damaging	0.921	Probably Damaging	2.66	Benign	0.02	Affected			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	0.2005	0.3539											-1.36	Neutral	0.992	Probably Damaging	0.921	Probably Damaging	2.66	Benign	0.02	Affected			1	0	-0.4	14.07
c.3584T>G	V1195G 2D AIThe SynGAP1 missense variant V1195G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Tools that agree on a benign effect are ESM1b and FATHMM. AlphaMissense‑Optimized is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, six of the eight evaluated tools predict pathogenicity while only two predict benign, and no high‑accuracy consensus or folding‑stability evidence contradicts this. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not conflict with the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250							-5.463	Likely Benign	0.881	Likely Pathogenic	Ambiguous	0.586	Likely Pathogenic	0.2005	0.2100											-2.81	Deleterious	0.998	Probably Damaging	1.000	Probably Damaging	5.55	Benign	0.01	Affected			-1	-3	-4.6	-42.08
c.1709C>A	A570D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570D is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000							-14.117	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.805	Likely Pathogenic	0.2006	0.2206		2.47	Destabilizing	1.2	2.33	Destabilizing	2.40	Destabilizing	1.36	Destabilizing	-5.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.28	Pathogenic	0.03	Affected			0	-2	-5.3	44.01
c.1411T>C	S471P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S471P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only polyPhen‑2 HumVar, whereas the remaining evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are 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 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	0.305330	Structured	0.355411	Uncertain	0.888	0.261	0.000							-12.379	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.530	Likely Pathogenic	0.2007	0.4769		3.65	Destabilizing	0.2	9.24	Destabilizing	6.45	Destabilizing	0.84	Ambiguous	-4.03	Deleterious	0.552	Possibly Damaging	0.141	Benign	-1.31	Pathogenic	0.05	Affected			1	-1	-0.8	10.04
c.2284G>C	D762H 2D AIThe SynGAP1 D762H missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125							-4.643	Likely Benign	0.909	Likely Pathogenic	Ambiguous	0.212	Likely Benign	0.2007	0.9102											-2.73	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.08	Pathogenic	0.02	Affected			1	-1	0.3	22.05
c.1615C>G	H539D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H539D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the only inconclusive result is FoldX, which is listed as uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000							-16.450	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.889	Likely Pathogenic	0.2008	0.0708		1.22	Ambiguous	0.2	3.27	Destabilizing	2.25	Destabilizing	1.08	Destabilizing	-8.05	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.25	Pathogenic	0.02	Affected			1	-1	-0.3	-22.05
c.1789T>A	F597I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F597I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010926	Structured	0.142961	Uncertain	0.944	0.151	0.000							-13.674	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.951	Likely Pathogenic	0.2008	0.1815		3.62	Destabilizing	0.9	2.15	Destabilizing	2.89	Destabilizing	1.45	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-2.18	Pathogenic	0.01	Affected			1	0	1.7	-34.02
c.2620C>A	Q874K 2D AIThe SynGAP1 missense variant Q874K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant. 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		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250							-6.379	Likely Benign	0.604	Likely Pathogenic	Likely Benign	0.169	Likely Benign	0.2008	0.4893											-2.35	Neutral	0.963	Probably Damaging	0.973	Probably Damaging	2.73	Benign	0.00	Affected			1	1	-0.4	0.04
c.3244C>A	Q1082K 2D AIThe SynGAP1 missense variant Q1082K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score benign, and AlphaMissense‑Optimized also predicts benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. No tools predict pathogenicity, and AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, while Foldetta results are unavailable. 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		0.819762	Disordered	0.979325	Binding	0.347	0.896	0.875							-4.488	Likely Benign	0.460	Ambiguous	Likely Benign	0.087	Likely Benign	0.2008	0.4972											-1.13	Neutral	0.224	Benign	0.058	Benign	4.19	Benign	0.12	Tolerated			1	1	-0.4	0.04
c.849G>C	E283D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E283D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and SIFT, whereas pathogenic predictions are made by AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and FoldX. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic. The Foldetta stability analysis is inconclusive and therefore treated as unavailable. Overall, the majority of evidence points to a pathogenic effect for E283D, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000							-10.190	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.280	Likely Benign	0.2008	0.3480		2.25	Destabilizing	0.2	0.94	Ambiguous	1.60	Ambiguous	0.60	Ambiguous	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.63	Pathogenic	0.06	Tolerated			3	2	0.0	-14.03
c.849G>T	E283D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and FoldX. Predictions that remain inconclusive are Foldetta, Rosetta, and premPS. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta’s stability analysis is uncertain. Overall, the preponderance of evidence indicates that E283D is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.358602	Uncertain	0.950	0.249	0.000							-10.190	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.280	Likely Benign	0.2008	0.3480		2.25	Destabilizing	0.2	0.94	Ambiguous	1.60	Ambiguous	0.60	Ambiguous	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.63	Pathogenic	0.06	Tolerated			3	2	0.0	-14.03
c.133A>C	N45H 2D AIThe SynGAP1 missense variant N45H 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 returns Benign, and the SGM‑Consensus (majority vote of 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 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		0.401658	Structured	0.431853	Uncertain	0.498	0.741	0.375							-2.620	Likely Benign	0.285	Likely Benign	Likely Benign	0.089	Likely Benign	0.2009	0.8046											-0.62	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.05	Benign	0.00	Affected			2	1	0.3	23.04
c.162C>A	N54K 2D AIThe SynGAP1 missense variant N54K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign) and is treated as unavailable. High‑accuracy methods show AlphaMissense‑Optimized as benign; Foldetta results are not provided, so its stability prediction is unavailable. Overall, the balance of evidence (five pathogenic vs. four benign predictions) suggests the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000							-8.252	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	0.084	Likely Benign	0.2010	0.5987											-0.82	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	4.23	Benign	0.00	Affected			1	0	-0.4	14.07
c.162C>G	N54K 2D AIThe SynGAP1 missense variant N54K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign) and is treated as unavailable. High‑accuracy methods show AlphaMissense‑Optimized as benign; Foldetta results are not provided, so its stability prediction is unavailable. Overall, the balance of evidence (five pathogenic vs. four benign predictions) suggests the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000							-8.252	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	0.084	Likely Benign	0.2010	0.5987											-0.82	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	4.23	Benign	0.00	Affected			1	0	-0.4	14.07
c.353T>A	M118K 2D AIThe SynGAP1 missense variant M118K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among 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 evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for M118K. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500							-3.979	Likely Benign	0.767	Likely Pathogenic	Likely Benign	0.276	Likely Benign	0.2010	0.1131											-2.98	Deleterious	0.396	Benign	0.099	Benign	3.84	Benign	0.01	Affected			0	-1	-5.8	-3.02
c.2885A>C	H962P 2D AIThe SynGAP1 missense variant H962P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.984483	Binding	0.369	0.886	0.750							-8.419	Likely Pathogenic	0.066	Likely Benign	Likely Benign	0.197	Likely Benign	0.2011	0.4352											-0.94	Neutral	0.748	Possibly Damaging	0.170	Benign	4.16	Benign	0.07	Tolerated			0	-2	1.6	-40.02
c.439C>A	Q147K 2D AIThe SynGAP1 missense variant Q147K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of available predictions lean toward a benign impact, and there is no ClinVar annotation to contradict this assessment. 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.			0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625							-12.562	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.084	Likely Benign	0.2012	0.3351											-2.12	Neutral	0.018	Benign	0.025	Benign	3.94	Benign	0.03	Affected			1	1	-0.4	0.04
c.695C>G	A232G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A232G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the change as benign include REVEL, FoldX, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Those that predict pathogenicity are polyPhen‑2 HumDiv and AlphaMissense‑Default. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, 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 Uncertain, SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.254060	Structured	0.307228	Uncertain	0.878	0.305	0.000							-4.924	Likely Benign	0.835	Likely Pathogenic	Ambiguous	0.453	Likely Benign	0.2012	0.4724		0.43	Likely Benign	0.1	1.43	Ambiguous	0.93	Ambiguous	0.53	Ambiguous	-1.39	Neutral	0.608	Possibly Damaging	0.172	Benign	5.81	Benign	0.11	Tolerated			1	0	-2.2	-14.03
c.1007A>C	K336T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336T 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 polyPhen‑2 HumVar. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy assessment shows AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for K336T, 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	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500							-13.468	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.212	Likely Benign	0.2014	0.4048		0.33	Likely Benign	0.1	-0.08	Likely Benign	0.13	Likely Benign	0.15	Likely Benign	-4.94	Deleterious	0.891	Possibly Damaging	0.315	Benign	1.58	Pathogenic	0.01	Affected			0	-1	3.2	-27.07
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	0.2014	0.5933											-0.21	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	2.64	Benign	0.04	Affected			1	-1	-0.8	10.04
c.2081C>G	A694G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000							-3.420	Likely Benign	0.144	Likely Benign	Likely Benign	0.093	Likely Benign	0.2015	0.3387		0.86	Ambiguous	0.0	1.16	Ambiguous	1.01	Ambiguous	0.86	Ambiguous	-1.90	Neutral	0.866	Possibly Damaging	0.171	Benign	3.50	Benign	0.05	Affected			1	0	-2.2	-14.03
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	0.2015	0.3738											-2.02	Neutral	0.989	Probably Damaging	0.874	Possibly Damaging	2.77	Benign	0.28	Tolerated			0	-2	1.6	-40.02
c.3488A>C	H1163P 2D AIThe SynGAP1 missense variant H1163P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are SIFT, ESM1b, and FATHMM, while those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, more tools predict pathogenicity than benignity (5 vs. 3), and there is no ClinVar record to contradict this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375							-2.023	Likely Benign	0.815	Likely Pathogenic	Ambiguous	0.578	Likely Pathogenic	0.2015	0.3900											-3.19	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.39	Benign	0.10	Tolerated			0	-2	1.6	-40.02
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	0.2015	0.3709											-3.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.81	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.2783A>C	Q928P 2D AIThe SynGAP1 missense variant Q928P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Based on the preponderance of pathogenic predictions and the SGM‑Consensus designation, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250							-6.275	Likely Benign	0.832	Likely Pathogenic	Ambiguous	0.441	Likely Benign	0.2016	0.5768											-4.28	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	1.54	Pathogenic	0.00	Affected			0	-1	1.9	-31.01
c.3961C>A	P1321T 2D AIThe SynGAP1 missense variant P1321T is catalogued in gnomAD (ID 6‑33451835‑C‑A) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.933505	Binding	0.463	0.828	0.875				6-33451835-C-A			-4.946	Likely Benign	0.074	Likely Benign	Likely Benign	0.058	Likely Benign	0.2016	0.5901											1.07	Neutral	0.115	Benign	0.012	Benign	4.25	Benign	1.00	Tolerated	3.77	5	-1	0	0.9	3.99
c.388C>A	Q130K 2D AIThe SynGAP1 missense variant Q130K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around benign: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate a benign effect, 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. High‑accuracy predictors—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign classification, whereas the pathogenic predictions come from polyPhen‑2 alone. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.718853	Binding	0.306	0.885	0.375							-4.656	Likely Benign	0.540	Ambiguous	Likely Benign	0.058	Likely Benign	0.2017	0.4473											-0.41	Neutral	0.924	Possibly Damaging	0.857	Possibly Damaging	4.20	Benign	0.07	Tolerated			1	1	-0.4	0.04
c.128G>A	G43D 2D AIThe SynGAP1 missense variant G43D is not 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 consistent with the lack of any ClinVar pathogenic classification. 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							-5.867	Likely Benign	0.204	Likely Benign	Likely Benign	0.082	Likely Benign	0.2018	0.2339											-0.84	Neutral	0.870	Possibly Damaging	0.500	Possibly Damaging	4.21	Benign	0.00	Affected			1	-1	-3.1	58.04
c.2102C>T	P701L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P701L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and ESM1b. The remaining tools (FoldX, Rosetta, AlphaMissense‑Default) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (7 benign vs. 3 pathogenic) and the two high‑accuracy benign calls suggest that the variant is most likely benign. This conclusion does not contradict any ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000							-10.185	Likely Pathogenic	0.515	Ambiguous	Likely Benign	0.116	Likely Benign	0.2018	0.5546		1.15	Ambiguous	0.0	-0.68	Ambiguous	0.24	Likely Benign	0.12	Likely Benign	-3.04	Deleterious	0.642	Possibly Damaging	0.087	Benign	3.50	Benign	0.09	Tolerated			-3	-3	5.4	16.04
c.3107A>C	Q1036P 2D AIThe SynGAP1 missense variant Q1036P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a damaging or pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and the consensus score indicates that the variant is most likely benign, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.987955	Binding	0.275	0.765	0.625							-2.491	Likely Benign	0.135	Likely Benign	Likely Benign	0.104	Likely Benign	0.2018	0.5564											-2.00	Neutral	0.802	Possibly Damaging	0.238	Benign	2.57	Benign	0.01	Affected			0	-1	1.9	-31.01
c.3916A>G	N1306D 2D AIThe SynGAP1 missense variant N1306D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.902190	Binding	0.367	0.888	0.875							-2.089	Likely Benign	0.207	Likely Benign	Likely Benign	0.143	Likely Benign	0.2018	0.4992											-3.43	Deleterious	0.001	Benign	0.010	Benign	2.58	Benign	0.00	Affected			2	1	0.0	0.98
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	0.631	Likely Pathogenic	0.2019	0.4291		-0.69	Ambiguous	0.1	0.14	Likely Benign	-0.28	Likely Benign	-0.13	Likely Benign	-3.81	Deleterious	0.994	Probably Damaging	0.994	Probably Damaging	-1.09	Pathogenic	0.23	Tolerated			0	1	-0.4	-0.94
c.2429G>T	R810L 2D AIThe SynGAP1 R810L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, while the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic outcome. Uncertain calls come from ESM1b and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in‑silico predictors points to a pathogenic impact for R810L. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375							-7.172	In-Between	0.834	Likely Pathogenic	Ambiguous	0.338	Likely Benign	0.2019	0.5271											-4.57	Deleterious	0.996	Probably Damaging	0.925	Probably Damaging	2.35	Pathogenic	0.01	Affected			-3	-2	8.3	-43.03
c.86T>A	M29K 2D AIThe SynGAP1 missense variant M29K is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency or clinical annotation. Prediction tools that converge on a benign outcome include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective predictions point to a benign effect, and this conclusion does not contradict the absence of a ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250							-2.514	Likely Benign	0.287	Likely Benign	Likely Benign	0.197	Likely Benign	0.2019	0.1312											-0.88	Neutral	0.018	Benign	0.184	Benign	4.27	Benign	0.00	Affected			0	-1	-5.8	-3.02
c.722A>C	K241T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Benign predictions are reported by Rosetta and FATHMM. Two tools (Foldetta and premPS) give uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenic; Foldetta remains uncertain. Overall, the consensus of the majority of evidence points to a pathogenic effect for K241T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000							-10.911	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.853	Likely Pathogenic	0.2021	0.3951		2.00	Destabilizing	0.4	0.06	Likely Benign	1.03	Ambiguous	0.60	Ambiguous	-5.14	Deleterious	0.995	Probably Damaging	0.747	Possibly Damaging	5.74	Benign	0.03	Affected			0	-1	3.2	-27.07
c.838T>C	Y280H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280H is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Among the available in‑silico predictors, none indicate a benign effect; all 14 tools that produced a classification predict pathogenicity: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive or missing. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125							-9.970	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.588	Likely Pathogenic	0.2021	0.0212		3.01	Destabilizing	0.3	2.58	Destabilizing	2.80	Destabilizing	1.95	Destabilizing	-4.60	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.94	Pathogenic	0.01	Affected			0	2	-1.9	-26.03
c.2883C>A	H961Q 2D AIThe SynGAP1 missense variant H961Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT and ESM1b predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is 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		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750							-8.368	Likely Pathogenic	0.118	Likely Benign	Likely Benign	0.088	Likely Benign	0.2022	0.3743											-0.49	Neutral	0.255	Benign	0.105	Benign	4.17	Benign	0.02	Affected			3	0	-0.3	-9.01
c.2883C>G	H961Q 2D AIThe SynGAP1 missense variant H961Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT and ESM1b predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority‑benign vote and is reported as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is 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 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		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750							-8.368	Likely Pathogenic	0.118	Likely Benign	Likely Benign	0.088	Likely Benign	0.2022	0.3743											-0.49	Neutral	0.255	Benign	0.105	Benign	4.17	Benign	0.02	Affected			3	0	-0.3	-9.01
c.3062A>C	Q1021P 2D AIThe SynGAP1 missense variant Q1021P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q1021P, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500							-3.522	Likely Benign	0.267	Likely Benign	Likely Benign	0.235	Likely Benign	0.2022	0.4789											-2.11	Neutral	0.996	Probably Damaging	0.992	Probably Damaging	2.56	Benign	0.02	Affected			0	-1	1.9	-31.01
c.1985A>G	Q662R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess sequence conservation, structural impact, or functional effect all converge on a benign outcome: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, FATHMM, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, FoldX, and Rosetta all predict benign. No tool in the dataset indicates pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Thus, based on the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000							-6.678	Likely Benign	0.300	Likely Benign	Likely Benign	0.159	Likely Benign	0.2023	0.1391		-0.41	Likely Benign	0.0	0.10	Likely Benign	-0.16	Likely Benign	-0.42	Likely Benign	0.49	Neutral	0.428	Benign	0.095	Benign	3.48	Benign	1.00	Tolerated			1	1	-1.0	28.06
c.382C>A	P128T 2D AIThe SynGAP1 missense variant P128T is listed in ClinVar with an “Uncertain” status (ClinVar ID 2801315.0) and is present in gnomAD (ID 6‑33432247‑C‑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, 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 (majority vote) 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 “Uncertain” classification. 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	Uncertain		1	6-33432247-C-A	1	6.20e-7	-4.217	Likely Benign	0.267	Likely Benign	Likely Benign	0.075	Likely Benign	0.2023	0.4053											-0.96	Neutral	0.952	Possibly Damaging	0.500	Possibly Damaging	4.19	Benign	0.35	Tolerated	3.74	4	-1	0	0.9	3.99
c.1319A>G	N440S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N440S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or likely benign. Only FoldX and premPS returned uncertain results, which are treated as unavailable. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. Consequently, 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	GAP	0.191378	Structured	0.267204	Uncertain	0.929	0.245	0.000							-1.753	Likely Benign	0.058	Likely Benign	Likely Benign	0.104	Likely Benign	0.2024	0.3556		0.52	Ambiguous	0.1	0.08	Likely Benign	0.30	Likely Benign	-0.50	Ambiguous	1.15	Neutral	0.001	Benign	0.000	Benign	3.53	Benign	0.92	Tolerated			1	1	2.7	-27.03
c.1471A>C	T491P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T491P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while premPS remains uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.325158	Uncertain	0.929	0.188	0.125							-13.603	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	0.882	Likely Pathogenic	0.2024	0.3759		3.19	Destabilizing	0.6	4.32	Destabilizing	3.76	Destabilizing	0.96	Ambiguous	-5.89	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.49	Pathogenic	0.00	Affected			0	-1	-0.9	-3.99
c.1631G>C	R544P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R544P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Across the available in‑silico predictors, none indicate a benign effect; all 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized 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. Consequently, the variant is most likely pathogenic based on current predictions, which contradicts the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038858	Structured	0.016004	Uncertain	0.967	0.333	0.000	Uncertain		2				-16.905	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.762	Likely Pathogenic	0.2024	0.3038		4.70	Destabilizing	0.1	4.19	Destabilizing	4.45	Destabilizing	1.14	Destabilizing	-4.88	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.48	Pathogenic	0.05	Affected	3.37	35	0	-2	2.9	-59.07	192.0	123.8	0.1	0.0	-0.3	0.0	X	X						Potentially Pathogenic	Arg544 is located in the middle of an α-helix (res. Ala533-Val560). In the WT simulations, the guanidinium side chain of Arg544 forms a salt bridge with the carboxylate groups of Glu548 on the same α-helix, and with Glu651 and Glu656 on an opposing α-helix (res. Glu666-Asp644). In the variant simulations, the pyrrolidine side chain of Pro544 cannot form any of the salt bridges that Arg544 does in the WT, potentially weakening the tertiary structure assembly. Additionally, Pro544 lacks the amide group, and thus, unlike Arg544 in the WT, is unable to form a hydrogen bond with the carbonyl of Gln540. This disruption breaks the continuity of the secondary structure element, causing the α-helix to bend slightly in the variant simulations. These negative structural effects could be more pronounced during protein folding and are likely to be undermined in the MD simulations.
c.1668C>A	N556K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556K is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, premPS, and SIFT, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions support a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000							-10.017	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.510	Likely Pathogenic	0.2024	0.2240		0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			1	0	-0.4	14.07
c.1668C>G	N556K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N556K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from FoldX, Rosetta, premPS, and SIFT; pathogenic predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is consistent with the absence of ClinVar annotation (i.e., no conflicting benign classification). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015078	Structured	0.008655	Uncertain	0.925	0.225	0.000							-10.017	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.510	Likely Pathogenic	0.2024	0.2240		0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			1	0	-0.4	14.07
c.628C>G	H210D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H210D is not 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. In contrast, the majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain, and Rosetta alone is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for H210D, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.144935	Structured	0.390904	Uncertain	0.872	0.298	0.125							-16.440	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.489	Likely Benign	0.2025	0.1255		0.13	Likely Benign	0.4	1.23	Ambiguous	0.68	Ambiguous	1.23	Destabilizing	-7.73	Deleterious	0.895	Possibly Damaging	0.533	Possibly Damaging	3.18	Benign	0.00	Affected			1	-1	-0.3	-22.05
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	0.227	Likely Benign	0.2026	0.3721		0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			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	0.227	Likely Benign	0.2026	0.3721		0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			3	2	0.0	-14.03
c.225G>C	E75D 2D AIThe SynGAP1 missense variant E75D is reported in gnomAD (6‑33425833‑G‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” No Foldetta stability prediction is available. Overall, the preponderance of evidence indicates that E75D is most likely benign, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.443881	Uncertain	0.303	0.822	0.500				6-33425833-G-C	1	6.20e-7	-3.710	Likely Benign	0.073	Likely Benign	Likely Benign	0.058	Likely Benign	0.2026	0.3833											-0.27	Neutral	0.001	Benign	0.000	Benign	4.25	Benign	0.00	Affected	4.32	1	2	3	0.0	-14.03
c.225G>T	E75D 2D AIThe SynGAP1 missense variant E75D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.443881	Uncertain	0.303	0.822	0.500							-3.710	Likely Benign	0.073	Likely Benign	Likely Benign	0.058	Likely Benign	0.2026	0.3833											-0.27	Neutral	0.001	Benign	0.000	Benign	4.25	Benign	0.00	Affected	4.32	1	2	3	0.0	-14.03
c.2632A>C	T878P 2D AIThe SynGAP1 missense variant T878P 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 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 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		0.622677	Disordered	0.628767	Binding	0.288	0.878	0.250							-3.130	Likely Benign	0.077	Likely Benign	Likely Benign	0.136	Likely Benign	0.2026	0.5538											-1.41	Neutral	0.761	Possibly Damaging	0.478	Possibly Damaging	2.96	Benign	0.01	Affected			0	-1	-0.9	-3.99
c.4022C>G	A1341G 2D AIThe SynGAP1 missense variant A1341G is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools overwhelmingly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), 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. Only the SIFT algorithm predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Taken together, the preponderance of evidence points to a benign effect for A1341G, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar record, which contains no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.980111	Binding	0.383	0.696	1.000							-3.334	Likely Benign	0.092	Likely Benign	Likely Benign	0.049	Likely Benign	0.2026	0.4541											-0.84	Neutral	0.006	Benign	0.011	Benign	4.12	Benign	0.05	Affected			1	0	-2.2	-14.03
c.353T>G	M118R 2D AIThe SynGAP1 missense variant M118R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, 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 balance of evidence leans toward a benign impact for M118R. This conclusion does not contradict any ClinVar annotation, as no ClinVar status is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500							-3.318	Likely Benign	0.698	Likely Pathogenic	Likely Benign	0.286	Likely Benign	0.2027	0.0913											-3.17	Deleterious	0.697	Possibly Damaging	0.202	Benign	3.83	Benign	0.00	Affected			0	-1	-6.4	24.99
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	0.794	Likely Pathogenic	0.2027	0.6475		0.93	Ambiguous	0.0	1.56	Ambiguous	1.25	Ambiguous	0.47	Likely Benign	-9.19	Deleterious	0.991	Probably Damaging	0.781	Possibly Damaging	5.81	Benign	0.00	Affected			-3	-3	5.4	16.04
c.896G>T	R299L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R299L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of consensus predictions favor a pathogenic effect, and the high‑accuracy tools do not overturn this trend. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for R299L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500							-5.171	Likely Benign	0.645	Likely Pathogenic	Likely Benign	0.356	Likely Benign	0.2027	0.5202		1.37	Ambiguous	0.6	0.77	Ambiguous	1.07	Ambiguous	0.59	Ambiguous	-4.03	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.02	Affected			-3	-2	8.3	-43.03
c.3317A>C	Q1106P 2D AIThe SynGAP1 missense variant Q1106P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence (5 benign vs 4 pathogenic predictions, with a benign high‑accuracy score and no contradictory ClinVar annotation) indicates that the variant is most likely benign. This conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.885302	Disordered	0.952043	Binding	0.382	0.870	0.875							-3.807	Likely Benign	0.077	Likely Benign	Likely Benign	0.162	Likely Benign	0.2029	0.5781											-3.14	Deleterious	0.996	Probably Damaging	0.988	Probably Damaging	1.75	Pathogenic	0.31	Tolerated			0	-1	1.9	-31.01
c.2702C>G	A901G 2D AIThe SynGAP1 missense variant A901G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of available predictions points to a benign impact, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.489838	Uncertain	0.306	0.917	0.375							-3.928	Likely Benign	0.127	Likely Benign	Likely Benign	0.047	Likely Benign	0.2030	0.5188											-1.52	Neutral	0.622	Possibly Damaging	0.165	Benign	2.61	Benign	0.37	Tolerated			1	0	-2.2	-14.03
c.1570T>C	C524R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C524R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Across the evaluated in‑silico tools, all pathogenic‑predicating algorithms—REVEL, SGM‑Consensus, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return a pathogenic or likely pathogenic verdict. The only tool with an inconclusive result is FoldX, which is treated as unavailable. High‑accuracy predictors reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.024729	Uncertain	0.916	0.385	0.125							-14.337	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.917	Likely Pathogenic	0.2031	0.1463		-0.53	Ambiguous	0.5	9.04	Destabilizing	4.26	Destabilizing	1.62	Destabilizing	-11.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.40	Pathogenic	0.00	Affected			-4	-3	-7.0	53.05
c.3314G>C	R1105P 2D AIThe SynGAP1 missense variant R1105P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN 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, PROVEAN) leans pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of predictions (six benign vs. two pathogenic) suggest a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.901269	Disordered	0.954396	Binding	0.330	0.863	0.875							-3.325	Likely Benign	0.425	Ambiguous	Likely Benign	0.149	Likely Benign	0.2031	0.5101											-3.22	Deleterious	0.007	Benign	0.006	Benign	2.44	Pathogenic	0.08	Tolerated			0	-2	2.9	-59.07
c.3334G>C	E1112Q 2D AIThe SynGAP1 missense variant E1112Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools points to a benign impact for E1112Q, 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		0.894241	Disordered	0.909381	Binding	0.335	0.902	0.875							-1.975	Likely Benign	0.364	Ambiguous	Likely Benign	0.102	Likely Benign	0.2031	0.7430											-0.48	Neutral	0.611	Possibly Damaging	0.305	Benign	2.71	Benign	0.42	Tolerated			2	2	0.0	-0.98
c.497C>A	A166D 2D AIThe SynGAP1 missense variant A166D is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus method SGM (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive, yielding a 2‑to‑2 split. AlphaMissense‑Optimized rates the variant as uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this change. Overall, the majority of tools predict a pathogenic impact, and there is no ClinVar annotation to contradict 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.			0.425610	Structured	0.505037	Binding	0.384	0.658	0.125							-12.171	Likely Pathogenic	0.900	Likely Pathogenic	Ambiguous	0.144	Likely Benign	0.2031	0.2694											-2.21	Neutral	0.877	Possibly Damaging	0.580	Possibly Damaging	4.02	Benign	0.01	Affected			0	-2	-5.3	44.01
c.2212A>G	S738G 2D AIThe SynGAP1 missense variant S738G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.441162	Uncertain	0.284	0.827	0.875							-3.863	Likely Benign	0.053	Likely Benign	Likely Benign	0.055	Likely Benign	0.2032	0.3385											-1.53	Neutral	0.002	Benign	0.003	Benign	2.66	Benign	0.01	Affected			1	0	0.4	-30.03
c.2714G>C	R905P 2D AIThe SynGAP1 missense variant R905P is 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. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.618085	Binding	0.291	0.920	0.250							-3.713	Likely Benign	0.701	Likely Pathogenic	Likely Benign	0.265	Likely Benign	0.2032	0.4616											-0.86	Neutral	1.000	Probably Damaging	0.977	Probably Damaging	2.64	Benign	0.07	Tolerated			0	-2	2.9	-59.07
c.3737A>C	K1246T 2D AIThe SynGAP1 missense variant K1246T 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 show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus of multiple independent predictors and the high‑accuracy tools—supports a benign classification for K1246T, 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	Coiled-coil	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625							-1.970	Likely Benign	0.263	Likely Benign	Likely Benign	0.101	Likely Benign	0.2032	0.2065											-2.19	Neutral	0.980	Probably Damaging	0.782	Possibly Damaging	2.65	Benign	0.02	Affected			0	-1	3.2	-27.07
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	0.2032	0.5249											-3.85	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.83	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.2765G>T	R922L 2D AIThe SynGAP1 missense variant R922L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy methods that are available—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign interpretation. Therefore, the variant is most likely benign according to the consensus of predictive tools, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.955308	Binding	0.277	0.845	0.375							-3.714	Likely Benign	0.546	Ambiguous	Likely Benign	0.150	Likely Benign	0.2033	0.5022											0.84	Neutral	0.983	Probably Damaging	0.828	Possibly Damaging	3.04	Benign	1.00	Tolerated			-3	-2	8.3	-43.03
c.3515A>C	H1172P 2D AIThe SynGAP1 missense variant H1172P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.673805	Binding	0.465	0.758	0.625							-2.871	Likely Benign	0.653	Likely Pathogenic	Likely Benign	0.403	Likely Benign	0.2033	0.4128											-2.09	Neutral	0.925	Possibly Damaging	0.529	Possibly Damaging	5.42	Benign	0.02	Affected			0	-2	1.6	-40.02
c.3288G>C	E1096D 2D AIThe SynGAP1 missense variant E1096D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign interpretation, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.976475	Binding	0.308	0.858	1.000							-3.818	Likely Benign	0.192	Likely Benign	Likely Benign	0.116	Likely Benign	0.2034	0.4994											-0.40	Neutral	0.115	Benign	0.052	Benign	2.71	Benign	0.38	Tolerated			3	2	0.0	-14.03
c.3288G>T	E1096D 2D AIThe SynGAP1 missense variant E1096D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion is not contradicted by any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.976475	Binding	0.308	0.858	1.000							-3.818	Likely Benign	0.192	Likely Benign	Likely Benign	0.116	Likely Benign	0.2034	0.4994											-0.40	Neutral	0.115	Benign	0.052	Benign	2.71	Benign	0.38	Tolerated			3	2	0.0	-14.03
c.425A>C	K142T 2D AIThe SynGAP1 missense variant K142T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500							-12.013	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.251	Likely Benign	0.2034	0.2708											-3.77	Deleterious	0.247	Benign	0.166	Benign	3.47	Benign	0.00	Affected			0	-1	3.2	-27.07
c.3137C>T	P1046L 2D AIThe SynGAP1 missense variant P1046L is reported in gnomAD (ID 6‑33443689‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, SIFT and FATHMM 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.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple independent predictors and the consensus analysis points to a benign classification. This conclusion is consistent with the absence of a ClinVar pathogenic report, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.970265	Disordered	0.942366	Binding	0.364	0.898	0.750				6-33443689-C-T	1	6.20e-7	-5.022	Likely Benign	0.116	Likely Benign	Likely Benign	0.100	Likely Benign	0.2036	0.6442											-2.11	Neutral	0.001	Benign	0.005	Benign	2.35	Pathogenic	0.05	Affected	3.77	5	-3	-3	5.4	16.04
c.3800T>C	M1267T 2D AIThe SynGAP1 missense variant M1267T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) likewise indicates likely pathogenicity. No Foldetta stability prediction is available for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-5.315	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic	0.270	Likely Benign	0.2036	0.1934											-5.00	Deleterious	0.982	Probably Damaging	0.672	Possibly Damaging	2.32	Pathogenic	0.00	Affected			-1	-1	-2.6	-30.09
c.2334C>A	N778K 2D AIThe SynGAP1 missense variant N778K is catalogued in gnomAD (ID 6‑33442492‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM; pathogenic predictions from PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome, reflecting the majority of benign calls. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, and Foldetta data are not available. Overall, the majority of evidence points toward a benign effect, and this is consistent with the lack of a ClinVar pathogenic classification. 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		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500				6-33442492-C-A			-6.768	Likely Benign	0.798	Likely Pathogenic	Ambiguous	0.113	Likely Benign	0.2037	0.5883											-1.57	Neutral	0.925	Possibly Damaging	0.932	Probably Damaging	4.27	Benign	0.18	Tolerated	3.64	6	0	1	-0.4	14.07
c.2334C>G	N778K 2D AIThe SynGAP1 missense variant N778K has no ClinVar record and is not listed in gnomAD. 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. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the preponderance of evidence points to a benign effect. 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 Benign		0.494003	Structured	0.853922	Binding	0.288	0.887	0.500							-6.768	Likely Benign	0.798	Likely Pathogenic	Ambiguous	0.114	Likely Benign	0.2037	0.5883											-1.57	Neutral	0.925	Possibly Damaging	0.932	Probably Damaging	4.27	Benign	0.18	Tolerated	3.64	6	0	1	-0.4	14.07
c.2753C>A	A918D 2D AIThe SynGAP1 missense variant A918D is not 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. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradictory ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.891459	Binding	0.317	0.860	0.250							-4.281	Likely Benign	0.445	Ambiguous	Likely Benign	0.102	Likely Benign	0.2037	0.2412											-0.99	Neutral	0.961	Probably Damaging	0.721	Possibly Damaging	2.64	Benign	0.01	Affected			0	-2	-5.3	44.01
c.3719G>C	R1240P 2D AIThe SynGAP1 missense variant R1240P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375							-16.120	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.473	Likely Benign	0.2037	0.3768											-5.45	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.66	Pathogenic	0.00	Affected			0	-2	2.9	-59.07
c.803T>G	I268S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a destabilizing, pathogenic effect. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000							-13.032	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.841	Likely Pathogenic	0.2037	0.0530		4.93	Destabilizing	0.1	4.54	Destabilizing	4.74	Destabilizing	2.10	Destabilizing	-5.34	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.53	Pathogenic	0.00	Affected			-1	-2	-5.3	-26.08
c.1258T>G	F420V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. In contrast, the majority of tools predict a pathogenic outcome: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic; the SGM‑Consensus itself is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts Pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy tool consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000							-11.849	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.402	Likely Benign	0.2038	0.2022		3.42	Destabilizing	0.1	3.35	Destabilizing	3.39	Destabilizing	1.58	Destabilizing	-6.41	Deleterious	0.495	Possibly Damaging	0.191	Benign	3.16	Benign	0.01	Affected			-1	-1	1.4	-48.04
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	0.168	Likely Benign	0.2038	0.3762		0.20	Likely Benign	0.1	0.07	Likely Benign	0.14	Likely Benign	0.02	Likely Benign	-1.83	Neutral	0.994	Probably Damaging	0.994	Probably Damaging	3.31	Benign	0.33	Tolerated			0	1	-0.4	-0.94
c.2020A>C	T674P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T674P missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The high‑accuracy AlphaMissense‑Optimized predicts benign, while Foldetta predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. No other high‑accuracy tool provides a definitive call. Consequently, the evidence is evenly split between benign and pathogenic, leaving the variant’s clinical significance uncertain. This uncertainty does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000							-8.661	Likely Pathogenic	0.109	Likely Benign	Likely Benign	0.143	Likely Benign	0.2039	0.6103		0.91	Ambiguous	0.6	4.12	Destabilizing	2.52	Destabilizing	0.12	Likely Benign	-2.69	Deleterious	0.995	Probably Damaging	0.891	Possibly Damaging	3.50	Benign	0.16	Tolerated			0	-1	-0.9	-3.99
c.2393C>T	P798L 2D AIThe SynGAP1 missense variant P798L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442945‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (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 (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; a Foldetta stability prediction is not available. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875	Uncertain		2	6-33442945-C-T	6	3.72e-6	-5.640	Likely Benign	0.074	Likely Benign	Likely Benign	0.042	Likely Benign	0.2039	0.5555											-0.86	Neutral	0.981	Probably Damaging	0.631	Possibly Damaging	4.21	Benign	0.00	Affected	4.32	1	-3	-3	5.4	16.04
c.1929G>C	E643D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E643D is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, FATHMM, and polyPhen2_HumVar. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen2_HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of predictions (8 benign vs. 5 pathogenic) support 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	0.033407	Structured	0.215915	Uncertain	0.871	0.315	0.000							-8.083	Likely Pathogenic	0.223	Likely Benign	Likely Benign	0.292	Likely Benign	0.2040	0.4276		0.46	Likely Benign	0.2	-0.34	Likely Benign	0.06	Likely Benign	1.09	Destabilizing	-2.96	Deleterious	0.694	Possibly Damaging	0.064	Benign	2.98	Benign	0.01	Affected			3	2	0.0	-14.03
c.1929G>T	E643D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E643D is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, FATHMM, and polyPhen2_HumVar. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen2_HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of predictions (8 benign vs. 5 pathogenic) support 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	0.033407	Structured	0.215915	Uncertain	0.871	0.315	0.000							-8.083	Likely Pathogenic	0.223	Likely Benign	Likely Benign	0.292	Likely Benign	0.2040	0.4276		0.46	Likely Benign	0.2	-0.34	Likely Benign	0.06	Likely Benign	1.09	Destabilizing	-2.96	Deleterious	0.694	Possibly Damaging	0.064	Benign	2.98	Benign	0.01	Affected			3	2	0.0	-14.03
c.1936C>A	L646M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome. Predictions that are inconclusive are FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, while Foldetta’s stability analysis remains uncertain. Overall, the evidence overwhelmingly supports a benign classification for this variant, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000							-1.911	Likely Benign	0.152	Likely Benign	Likely Benign	0.106	Likely Benign	0.2041	0.3427		0.70	Ambiguous	0.1	1.66	Ambiguous	1.18	Ambiguous	-1.10	Stabilizing	1.86	Neutral	0.211	Benign	0.055	Benign	3.57	Benign	1.00	Tolerated			4	2	-1.9	18.03
c.2758C>A	Q920K 2D AIThe SynGAP1 missense variant Q920K is not 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 Q920K, 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		0.699094	Disordered	0.927260	Binding	0.306	0.845	0.250							-4.234	Likely Benign	0.380	Ambiguous	Likely Benign	0.145	Likely Benign	0.2041	0.4331											-1.72	Neutral	0.771	Possibly Damaging	0.412	Benign	2.67	Benign	0.00	Affected			1	1	-0.4	0.04
c.3233T>G	V1078G 2D AIThe SynGAP1 missense variant V1078G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign (3 benign vs 1 pathogenic). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence indicates a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750							-3.270	Likely Benign	0.699	Likely Pathogenic	Likely Benign	0.168	Likely Benign	0.2041	0.2693											-0.54	Neutral	0.157	Benign	0.292	Benign	3.85	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.108T>A	H36Q 2D AIThe SynGAP1 missense variant H36Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: 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 effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375							-3.642	Likely Benign	0.135	Likely Benign	Likely Benign	0.044	Likely Benign	0.2042	0.4572											-0.16	Neutral	0.182	Benign	0.046	Benign	4.34	Benign	0.00	Affected			3	0	-0.3	-9.01
c.108T>G	H36Q 2D AIThe SynGAP1 missense variant H36Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: 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 effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375							-3.642	Likely Benign	0.135	Likely Benign	Likely Benign	0.044	Likely Benign	0.2042	0.4572											-0.16	Neutral	0.182	Benign	0.046	Benign	4.34	Benign	0.00	Affected			3	0	-0.3	-9.01
c.2948G>C	S983T 2D AIThe SynGAP1 missense variant S983T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Overall, the balance of evidence leans toward pathogenicity, with five tools supporting a deleterious effect versus four supporting benign. This prediction does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625							-4.493	Likely Benign	0.588	Likely Pathogenic	Likely Benign	0.172	Likely Benign	0.2042	0.5517											-1.65	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.08	Pathogenic	0.00	Affected			1	1	0.1	14.03
c.3124C>G	Q1042E 2D AIThe SynGAP1 missense variant Q1042E is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.959333	Binding	0.310	0.846	0.625							-4.231	Likely Benign	0.262	Likely Benign	Likely Benign	0.267	Likely Benign	0.2042	0.3276											-1.12	Neutral	0.224	Benign	0.077	Benign	5.44	Benign	0.15	Tolerated			2	2	0.0	0.98
c.794A>C	K265T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265T missense variant is reported in gnomAD (ID 6‑33437699‑A‑C) but has no ClinVar entry. Prediction tools that classify the variant as benign include REVEL, SIFT, and Rosetta. Those that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Four tools give uncertain results: FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. 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	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000				6-33437699-A-C	1	6.20e-7	-9.425	Likely Pathogenic	0.839	Likely Pathogenic	Ambiguous	0.441	Likely Benign	0.2042	0.3178		0.99	Ambiguous	0.1	0.37	Likely Benign	0.68	Ambiguous	0.83	Ambiguous	-3.75	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.07	Tolerated	3.38	18	-1	0	3.2	-27.07
c.10T>C	S4P 2D AIThe SynGAP1 missense variant S4P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools largely support a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, 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, two tools—polyPhen‑2 HumDiv and SIFT—predict a pathogenic impact. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.547364	Binding	0.390	0.924	0.750							-4.131	Likely Benign	0.114	Likely Benign	Likely Benign	0.153	Likely Benign	0.2043	0.6112											-0.33	Neutral	0.676	Possibly Damaging	0.307	Benign	4.12	Benign	0.00	Affected			1	-1	-0.8	10.04
c.2806G>C	A936P 2D AIThe SynGAP1 missense variant A936P is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all classify the change as benign or likely benign. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. No Foldetta stability prediction is available. Overall, the computational evidence overwhelmingly 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 any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.973218	Binding	0.319	0.874	0.625							-2.782	Likely Benign	0.191	Likely Benign	Likely Benign	0.014	Likely Benign	0.2043	0.6109											-1.28	Neutral	0.012	Benign	0.011	Benign	2.46	Pathogenic	0.06	Tolerated			1	-1	-3.4	26.04
c.3392C>T	P1131L 2D AIThe SynGAP1 missense variant P1131L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy AlphaMissense‑Optimized tool classifies the variant as benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also 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 preponderance of evidence points to a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.855155	Binding	0.360	0.899	0.750							-5.267	Likely Benign	0.420	Ambiguous	Likely Benign	0.293	Likely Benign	0.2043	0.6998											-3.62	Deleterious	0.002	Benign	0.005	Benign	5.26	Benign	0.00	Affected			-3	-3	5.4	16.04
c.3458G>C	R1153P 2D AIThe SynGAP1 missense variant R1153P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that R1153P is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625							-2.431	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic	0.384	Likely Benign	0.2043	0.4315											-5.01	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.47	Pathogenic	0.00	Affected			0	-2	2.9	-59.07
c.3418A>C	T1140P 2D AIThe SynGAP1 missense variant T1140P 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 further support a benign interpretation: 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 T1140P, and this conclusion 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		0.926919	Disordered	0.708094	Binding	0.293	0.854	1.000							-1.921	Likely Benign	0.126	Likely Benign	Likely Benign	0.058	Likely Benign	0.2044	0.3837											-1.49	Neutral	0.761	Possibly Damaging	0.478	Possibly Damaging	2.61	Benign	0.32	Tolerated			0	-1	-0.9	-3.99
c.2880C>A	H960Q 2D AIThe SynGAP1 missense variant H960Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.987911	Disordered	0.983385	Binding	0.380	0.901	0.750							-8.551	Likely Pathogenic	0.124	Likely Benign	Likely Benign	0.109	Likely Benign	0.2045	0.3993											-0.79	Neutral	0.748	Possibly Damaging	0.170	Benign	4.20	Benign	0.21	Tolerated			3	0	-0.3	-9.01
c.2880C>G	H960Q 2D AIThe SynGAP1 missense variant H960Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.987911	Disordered	0.983385	Binding	0.380	0.901	0.750							-8.551	Likely Pathogenic	0.124	Likely Benign	Likely Benign	0.109	Likely Benign	0.2045	0.3993											-0.79	Neutral	0.748	Possibly Damaging	0.170	Benign	4.20	Benign	0.21	Tolerated			3	0	-0.3	-9.01
c.3305C>A	A1102D 2D AIThe SynGAP1 missense variant A1102D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and 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 preponderance of evidence indicates that the variant is most likely benign, 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.			0.915074	Disordered	0.962659	Binding	0.388	0.859	0.875							-4.647	Likely Benign	0.388	Ambiguous	Likely Benign	0.081	Likely Benign	0.2045	0.2984											-1.38	Neutral	0.033	Benign	0.028	Benign	2.27	Pathogenic	0.12	Tolerated			0	-2	-5.3	44.01
c.3410A>C	H1137P 2D AIThe SynGAP1 missense variant H1137P is listed in ClinVar as a benign alteration (ClinVar ID 3685596.0) and is present in the gnomAD database (gnomAD ID 6‑33444445‑A‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (derived from the same four high‑accuracy predictors) also indicates benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions, including the most reliable tools, support a benign classification, which is consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.756488	Binding	0.314	0.879	0.875	Benign		1	6-33444445-A-C	12	7.44e-6	-2.098	Likely Benign	0.054	Likely Benign	Likely Benign	0.419	Likely Benign	0.2045	0.4501											-1.93	Neutral	0.925	Possibly Damaging	0.703	Possibly Damaging	5.29	Benign	0.00	Affected	4.32	4	-2	0	1.6	-40.02
c.74G>T	R25L 2D AIThe SynGAP1 missense variant R25L is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict a pathogenic impact. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy tools specifically highlight a benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta data are missing. Taken together, the majority of robust predictors and the consensus analysis support a benign classification for R25L. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375							-3.443	Likely Benign	0.484	Ambiguous	Likely Benign	0.121	Likely Benign	0.2045	0.4792											-1.59	Neutral	0.686	Possibly Damaging	0.630	Possibly Damaging	3.97	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.2912C>T	P971L 2D AIThe SynGAP1 missense variant P971L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625							-4.892	Likely Benign	0.070	Likely Benign	Likely Benign	0.030	Likely Benign	0.2046	0.5985											-1.57	Neutral	0.144	Benign	0.026	Benign	3.93	Benign	0.00	Affected			-3	-3	5.4	16.04
c.3221A>C	Q1074P 2D AIThe SynGAP1 missense variant Q1074P is listed in gnomAD (ID 6‑33443773‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single outlier. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.987006	Binding	0.339	0.897	0.750				6-33443773-A-C	1	6.23e-7	-4.259	Likely Benign	0.083	Likely Benign	Likely Benign	0.188	Likely Benign	0.2046	0.5784											0.52	Neutral	0.925	Possibly Damaging	0.432	Benign	2.66	Benign	0.13	Tolerated	3.77	5	-1	0	1.9	-31.01
c.3302C>A	P1101H 2D AIThe SynGAP1 missense variant P1101H 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 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 majority of evidence points to a benign effect for P1101H, 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		0.874069	Disordered	0.968967	Binding	0.457	0.861	0.875							-5.370	Likely Benign	0.149	Likely Benign	Likely Benign	0.167	Likely Benign	0.2046	0.4597											-1.87	Neutral	0.996	Probably Damaging	0.864	Possibly Damaging	4.18	Benign	0.02	Affected			0	-2	-1.6	40.02
c.163C>A	Q55K 2D AIThe SynGAP1 missense variant Q55K is listed in ClinVar (ID 520688.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33423572‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000	Uncertain		2	6-33423572-C-A	24	1.49e-5	-5.840	Likely Benign	0.612	Likely Pathogenic	Likely Benign	0.085	Likely Benign	0.2047	0.4129											-1.21	Neutral	0.140	Benign	0.184	Benign	3.91	Benign	0.00	Affected	4.32	1	1	1	-0.4	0.04
c.269T>G	V90G 2D AIThe SynGAP1 missense variant V90G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign verdict. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500							-2.617	Likely Benign	0.358	Ambiguous	Likely Benign	0.094	Likely Benign	0.2047	0.2936											-0.55	Neutral	0.024	Benign	0.208	Benign	4.00	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.2923A>C	T975P 2D AIThe SynGAP1 missense variant T975P has no ClinVar entry and is not reported in gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.969331	Binding	0.332	0.890	0.625							-2.181	Likely Benign	0.071	Likely Benign	Likely Benign	0.286	Likely Benign	0.2047	0.4758											-1.21	Neutral	0.000	Benign	0.002	Benign	4.14	Benign	0.06	Tolerated			0	-1	-0.9	-3.99
c.3200C>T	P1067L 2D AIThe SynGAP1 missense variant P1067L is not 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, 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. Overall, the majority of predictions and the consensus analysis indicate a benign impact. This conclusion is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.966441	Disordered	0.975099	Binding	0.459	0.907	0.875							-4.461	Likely Benign	0.107	Likely Benign	Likely Benign	0.157	Likely Benign	0.2047	0.6198											-3.01	Deleterious	0.951	Possibly Damaging	0.619	Possibly Damaging	2.76	Benign	0.01	Affected			-3	-3	5.4	16.04
c.3866A>C	K1289T 2D AIThe SynGAP1 missense variant K1289T is not reported in ClinVar and is absent from gnomAD. Consensus prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized 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. No Foldetta stability prediction is available for this residue. Overall, the majority of computational evidence points to a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625							-3.618	Likely Benign	0.250	Likely Benign	Likely Benign	0.094	Likely Benign	0.2047	0.2447											-2.18	Neutral	0.369	Benign	0.120	Benign	2.58	Benign	0.02	Affected			0	-1	3.2	-27.07
c.3263G>C	S1088T 2D AIThe SynGAP1 missense variant S1088T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to 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		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000							-4.569	Likely Benign	0.295	Likely Benign	Likely Benign	0.175	Likely Benign	0.2048	0.6514											-1.32	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	2.71	Benign	0.04	Affected			1	1	0.1	14.03
c.140G>C	R47P 2D AIThe SynGAP1 missense variant R47P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant and is likewise unavailable. High‑accuracy tools specifically indicate a benign prediction from AlphaMissense‑Optimized, while the other high‑accuracy methods (SGM Consensus, Foldetta) provide no definitive assessment. Overall, the balance of evidence (five pathogenic vs. four benign predictions) suggests the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125							-10.316	Likely Pathogenic	0.746	Likely Pathogenic	Likely Benign	0.195	Likely Benign	0.2050	0.4956											-1.63	Neutral	0.841	Possibly Damaging	0.809	Possibly Damaging	4.02	Benign	0.00	Affected			0	-2	2.9	-59.07
c.3049T>A	F1017I 2D AIThe SynGAP1 missense variant F1017I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of conventional tools (5 pathogenic vs 4 benign) lean toward pathogenicity, but the single high‑accuracy benign prediction introduces uncertainty. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.889439	Disordered	0.954171	Binding	0.322	0.801	0.625							-3.244	Likely Benign	0.584	Likely Pathogenic	Likely Benign	0.113	Likely Benign	0.2050	0.1969											-2.55	Deleterious	0.951	Possibly Damaging	0.710	Possibly Damaging	2.50	Benign	0.05	Affected			1	0	1.7	-34.02
c.1427T>G	F476C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476C is catalogued in gnomAD (ID 6‑33438459‑T‑G) but has no ClinVar entry. Functional prediction tools split in two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, seven tools predict pathogenicity versus six predicting benign, with no ClinVar evidence to contradict this assessment. Thus, the variant is most likely pathogenic based on the current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000				6-33438459-T-G			-9.270	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	0.280	Likely Benign	0.2051	0.1251		2.05	Destabilizing	0.1	2.62	Destabilizing	2.34	Destabilizing	-0.30	Likely Benign	2.69	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	3.46	Benign	0.83	Tolerated	3.40	22	-2	-4	-0.3	-44.04
c.1469C>G	A490G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Pathogenic). Predictions that are uncertain or inconclusive 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 evidence points to a pathogenic impact for A490G. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125							-9.767	Likely Pathogenic	0.384	Ambiguous	Likely Benign	0.744	Likely Pathogenic	0.2051	0.2228		1.24	Ambiguous	0.0	2.00	Destabilizing	1.62	Ambiguous	1.13	Destabilizing	-3.44	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.46	Pathogenic	0.01	Affected			1	0	-2.2	-14.03
c.3628C>G	H1210D 2D AIThe SynGAP1 missense variant H1210D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. 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 balance of evidence leans toward a benign impact, with no conflict with ClinVar status (which has no entry for this variant). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.599170	Disordered	0.587579	Binding	0.900	0.567	0.375							-7.092	In-Between	0.530	Ambiguous	Likely Benign	0.126	Likely Benign	0.2051	0.1646											-2.98	Deleterious	0.680	Possibly Damaging	0.206	Benign	2.70	Benign	0.02	Affected			1	-1	-0.3	-22.05
c.776G>C	R259P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R259P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods further support this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic based on the collective computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.338208	Uncertain	0.885	0.255	0.250							-14.876	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.902	Likely Pathogenic	0.2051	0.5249		6.34	Destabilizing	1.6	3.78	Destabilizing	5.06	Destabilizing	1.16	Destabilizing	-6.43	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	5.84	Benign	0.00	Affected			0	-2	2.9	-59.07
c.1069C>A	H357N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357N 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, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Taken together, the overwhelming majority of evidence points to a benign impact. There is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250							-7.617	In-Between	0.103	Likely Benign	Likely Benign	0.126	Likely Benign	0.2052	0.3266		0.14	Likely Benign	0.2	0.31	Likely Benign	0.23	Likely Benign	0.31	Likely Benign	-1.47	Neutral	0.495	Possibly Damaging	0.169	Benign	4.25	Benign	0.15	Tolerated			2	1	-0.3	-23.04
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	0.275	Likely Benign	0.2052	0.4120		0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			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	0.273	Likely Benign	0.2052	0.4120		0.22	Likely Benign	0.1	1.02	Ambiguous	0.62	Ambiguous	0.39	Likely Benign	-2.72	Deleterious	0.985	Probably Damaging	0.426	Benign	3.41	Benign	0.06	Tolerated			3	2	0.0	-14.03
c.2752G>C	A918P 2D AIThe SynGAP1 missense variant A918P 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		0.632174	Disordered	0.891459	Binding	0.317	0.860	0.250							-2.087	Likely Benign	0.087	Likely Benign	Likely Benign	0.136	Likely Benign	0.2052	0.4985											-0.60	Neutral	0.998	Probably Damaging	0.924	Probably Damaging	2.59	Benign	0.04	Affected			1	-1	-3.4	26.04
c.404G>C	R135P 2D AIThe SynGAP1 missense variant R135P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors that classify the variant as benign include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy tools give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.676514	Binding	0.380	0.898	0.250							-9.512	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.139	Likely Benign	0.2052	0.4535											-3.19	Deleterious	0.609	Possibly Damaging	0.308	Benign	3.68	Benign	0.01	Affected			0	-2	2.9	-59.07
c.940T>A	F314I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a pathogenic effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict deleterious or pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Tools with uncertain or inconclusive results include Rosetta, Foldetta, and ESM1b. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, while Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation (i.e., no benign classification). Therefore, the variant is most likely pathogenic, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125							-7.059	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.534	Likely Pathogenic	0.2052	0.2308		2.23	Destabilizing	0.4	1.08	Ambiguous	1.66	Ambiguous	1.31	Destabilizing	-4.98	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.26	Pathogenic	0.01	Affected			1	0	1.7	-34.02
c.1258T>C	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise the SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated predictors (six pathogenic vs. five benign) indicate that F420L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000							-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.262	Likely Benign	0.2053	0.3016		1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1260T>A	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise the SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated predictors (six pathogenic vs. five benign) indicate that F420L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000							-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.146	Likely Benign	0.2053	0.3016		1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1260T>G	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is listed in ClinVar (ID 1397885.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Those that predict a pathogenic effect comprise premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, Foldetta) yield inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus also as pathogenic, while Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar “Uncertain” status but suggests the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000	Uncertain		1				-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.146	Likely Benign	0.2053	0.3016		1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.43G>A	A15T 2D AIThe SynGAP1 missense variant A15T is listed in ClinVar (ID 1925632.0) with an “Uncertain” clinical significance and is present in gnomAD (6‑33420307‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.466055	Uncertain	0.330	0.912	0.375	Uncertain		1	6-33420307-G-A	4	2.60e-6	-3.720	Likely Benign	0.125	Likely Benign	Likely Benign	0.086	Likely Benign	0.2053	0.7423											-0.08	Neutral	0.602	Possibly Damaging	0.017	Benign	4.16	Benign	0.00	Affected	4.32	1	1	0	-2.5	30.03
c.1705T>G	F569V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F569V is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000							-14.248	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.874	Likely Pathogenic	0.2054	0.1422		4.74	Destabilizing	0.2	5.40	Destabilizing	5.07	Destabilizing	1.73	Destabilizing	-6.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.29	Pathogenic	0.00	Affected			-1	-1	1.4	-48.04
c.2861C>A	P954H 2D AIThe SynGAP1 missense variant P954H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar or gnomAD entries—there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984159	Disordered	0.932268	Binding	0.465	0.926	0.750							-3.670	Likely Benign	0.082	Likely Benign	Likely Benign	0.098	Likely Benign	0.2054	0.4756											-0.50	Neutral	0.041	Benign	0.067	Benign	2.75	Benign	0.04	Affected			0	-2	-1.6	40.02
c.940T>G	F314V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F314V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). All available in silico predictors classify the variant as pathogenic: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta—each return a pathogenic prediction. No predictions or stability results are missing or inconclusive. Based on the unanimous pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.374049	Uncertain	0.900	0.271	0.125							-8.907	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.594	Likely Pathogenic	0.2054	0.2075		3.31	Destabilizing	0.4	2.54	Destabilizing	2.93	Destabilizing	1.44	Destabilizing	-5.90	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.26	Pathogenic	0.00	Affected			-1	-1	1.4	-48.04
c.1536A>C	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E512D is not reported in ClinVar or gnomAD. Across a broad panel of in silico predictors, the majority indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Only the ESM1b model assigns a pathogenic label, while Rosetta and Foldetta provide uncertain results. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta remains inconclusive. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000							-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.259	Likely Benign	0.2055	0.3089		0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			3	2	0.0	-14.03
c.1536A>T	E512D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E512D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Across the broad panel of in‑silico predictors, the majority (REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as benign, whereas only ESM1b predicts it as pathogenic. The high‑accuracy tools give a consistent benign signal: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Overall, the evidence strongly supports a benign effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000							-8.354	Likely Pathogenic	0.198	Likely Benign	Likely Benign	0.259	Likely Benign	0.2055	0.3089		0.12	Likely Benign	0.3	1.05	Ambiguous	0.59	Ambiguous	0.00	Likely Benign	-2.10	Neutral	0.016	Benign	0.012	Benign	3.34	Benign	0.23	Tolerated			3	2	0.0	-14.03
c.3158G>C	S1053T 2D AIThe SynGAP1 missense variant S1053T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign impact for S1053T, 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		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875							-6.209	Likely Benign	0.076	Likely Benign	Likely Benign	0.223	Likely Benign	0.2055	0.5976											-0.25	Neutral	0.625	Possibly Damaging	0.249	Benign	5.32	Benign	0.70	Tolerated			1	1	0.1	14.03
c.3257C>T	P1086L 2D AIThe SynGAP1 missense variant P1086L is not reported in ClinVar (ClinVar status: not present) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, 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 lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which simply indicates the variant has not yet been reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000							-4.694	Likely Benign	0.607	Likely Pathogenic	Likely Benign	0.166	Likely Benign	0.2055	0.6326											-3.57	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.73	Benign	0.00	Affected			-3	-3	5.4	16.04
c.3641G>C	R1214P 2D AIThe SynGAP1 missense variant R1214P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for R1214P. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.506868	Binding	0.903	0.566	0.375							-16.520	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.161	Likely Benign	0.2055	0.3077											-4.09	Deleterious	0.998	Probably Damaging	0.939	Probably Damaging	2.47	Pathogenic	0.01	Affected			0	-2	2.9	-59.07
c.1238C>T	P413L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P413L 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, and FATHMM. Those that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000							-12.735	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.461	Likely Benign	0.2056	0.5614		2.61	Destabilizing	0.4	1.34	Ambiguous	1.98	Ambiguous	0.30	Likely Benign	-9.21	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.19	Benign	0.00	Affected			-3	-3	5.4	16.04
c.3010C>A	H1004N 2D AIThe SynGAP1 missense variant H1004N is 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		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750							-4.265	Likely Benign	0.601	Likely Pathogenic	Likely Benign	0.072	Likely Benign	0.2056	0.3580											-1.18	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.88	Benign	0.35	Tolerated			2	1	-0.3	-23.04
c.2987C>T	P996L 2D AIThe SynGAP1 missense variant P996L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.775545	Disordered	0.942262	Binding	0.312	0.900	0.750							-5.302	Likely Benign	0.083	Likely Benign	Likely Benign	0.045	Likely Benign	0.2057	0.6631											-1.65	Neutral	0.000	Benign	0.001	Benign	4.25	Benign	0.02	Affected			-3	-3	5.4	16.04
c.815G>C	R272P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R272P 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, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the single uncertain call (premPS) does not alter the overall consensus. 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, and PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.071867	Structured	0.425620	Uncertain	0.925	0.215	0.125							-11.812	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.561	Likely Pathogenic	0.2057	0.4102		5.64	Destabilizing	0.2	3.99	Destabilizing	4.82	Destabilizing	0.80	Ambiguous	-3.95	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.74	Pathogenic	0.01	Affected			0	-2	2.9	-59.07
c.2898C>A	H966Q 2D AIThe SynGAP1 missense variant H966Q is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts 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 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 H966Q 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		0.976962	Disordered	0.974672	Binding	0.378	0.879	0.750							-5.662	Likely Benign	0.100	Likely Benign	Likely Benign	0.113	Likely Benign	0.2058	0.3914											-0.66	Neutral	0.748	Possibly Damaging	0.232	Benign	4.06	Benign	0.45	Tolerated			3	0	-0.3	-9.01
c.2898C>G	H966Q 2D AIThe SynGAP1 missense variant H966Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates 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 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 any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.976962	Disordered	0.974672	Binding	0.378	0.879	0.750							-5.662	Likely Benign	0.100	Likely Benign	Likely Benign	0.113	Likely Benign	0.2058	0.3914											-0.66	Neutral	0.748	Possibly Damaging	0.232	Benign	4.06	Benign	0.45	Tolerated			3	0	-0.3	-9.01
c.1454G>C	R485P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R485P is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return pathogenic or likely pathogenic scores. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.188120	Structured	0.377409	Uncertain	0.805	0.246	0.125							-16.356	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.692	Likely Pathogenic	0.2059	0.3941		5.26	Destabilizing	0.3	6.86	Destabilizing	6.06	Destabilizing	0.56	Ambiguous	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.94	Pathogenic	0.00	Affected			0	-2	2.9	-59.07
c.184G>C	D62H 2D AIThe SynGAP1 missense variant D62H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates 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 predictions, D62H 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		0.425610	Structured	0.476010	Uncertain	0.575	0.720	0.125							-5.253	Likely Benign	0.511	Ambiguous	Likely Benign	0.070	Likely Benign	0.2059	0.6579											-1.53	Neutral	0.172	Benign	0.248	Benign	4.05	Benign	0.00	Affected			1	-1	0.3	22.05
c.3278A>C	Q1093P 2D AIThe SynGAP1 missense variant Q1093P is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors classifies it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic effect. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized scores benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely benign, while Foldetta stability analysis is unavailable. Overall, the evidence points to a benign effect for Q1093P, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983312	Binding	0.351	0.886	1.000							-2.613	Likely Benign	0.080	Likely Benign	Likely Benign	0.137	Likely Benign	0.2059	0.5956											-0.96	Neutral	0.001	Benign	0.001	Benign	2.69	Benign	0.05	Affected			0	-1	1.9	-31.01
c.2473T>C	S825P 2D AIThe SynGAP1 missense variant S825P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S825P is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750							-3.227	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic	0.285	Likely Benign	0.2060	0.5998											-3.12	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.94	Pathogenic	0.02	Affected			1	-1	-0.8	10.04
c.482C>A	P161H 2D AIThe SynGAP1 missense variant P161H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that P161H 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		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375							-12.103	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.291	Likely Benign	0.2060	0.4039											-4.22	Deleterious	0.964	Probably Damaging	0.650	Possibly Damaging	3.89	Benign	0.00	Affected			0	-2	-1.6	40.02
c.1280A>C	H427P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Two tools are uncertain: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate a pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification for H427P, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000							-11.098	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.324	Likely Benign	0.2061	0.3442		4.74	Destabilizing	0.1	7.61	Destabilizing	6.18	Destabilizing	0.68	Ambiguous	-4.22	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.51	Benign	0.01	Affected			0	-2	1.6	-40.02
c.1673A>C	H558P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H558P is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are SIFT and AlphaMissense‑Optimized; those that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Overall, the majority of tools, including the high‑accuracy ones, indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.033407	Structured	0.011039	Uncertain	0.897	0.200	0.000							-13.706	Likely Pathogenic	0.675	Likely Pathogenic	Likely Benign	0.782	Likely Pathogenic	0.2061	0.2405		0.63	Ambiguous	0.2	6.93	Destabilizing	3.78	Destabilizing	0.94	Ambiguous	-6.28	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	-1.25	Pathogenic	0.09	Tolerated			0	-2	1.6	-40.02
c.2882A>C	H961P 2D AIThe SynGAP1 missense variant H961P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while only SIFT and ESM1b predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Consequently, the collective evidence indicates that H961P is most likely benign, and this conclusion is not in conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750							-8.434	Likely Pathogenic	0.071	Likely Benign	Likely Benign	0.210	Likely Benign	0.2061	0.4701											-0.58	Neutral	0.000	Benign	0.000	Benign	4.15	Benign	0.02	Affected			0	-2	1.6	-40.02
c.1001A>C	K334T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334T 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, Rosetta, and premPS. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain. Overall, the majority of evidence points to 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.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500							-8.313	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.320	Likely Benign	0.2062	0.2978		0.78	Ambiguous	0.3	0.21	Likely Benign	0.50	Ambiguous	0.17	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.02	Affected			0	-1	3.2	-27.07
c.2803G>C	A935P 2D AIThe SynGAP1 missense variant A935P is not 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, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, 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.			0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625							-3.239	Likely Benign	0.371	Ambiguous	Likely Benign	0.269	Likely Benign	0.2062	0.5466											-2.08	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.29	Pathogenic	0.00	Affected			1	-1	-3.4	26.04
c.293A>C	H98P 2D AIThe SynGAP1 missense variant H98P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.631713	Binding	0.348	0.872	0.625							-1.460	Likely Benign	0.069	Likely Benign	Likely Benign	0.275	Likely Benign	0.2062	0.4669											-0.83	Neutral	0.659	Possibly Damaging	0.024	Benign	4.20	Benign	0.00	Affected			0	-2	1.6	-40.02
c.2276T>C	M759T 2D AIThe SynGAP1 missense variant M759T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the SGM consensus and AlphaMissense‑Optimized—supports a benign classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375							-4.202	Likely Benign	0.380	Ambiguous	Likely Benign	0.197	Likely Benign	0.2063	0.1534											-1.90	Neutral	0.891	Possibly Damaging	0.315	Benign	2.58	Benign	0.08	Tolerated			-1	-1	-2.6	-30.09
c.3443T>C	M1148T 2D AIThe SynGAP1 missense variant M1148T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.774279	Binding	0.343	0.835	0.875							-0.972	Likely Benign	0.159	Likely Benign	Likely Benign	0.151	Likely Benign	0.2063	0.2214											-1.50	Neutral	0.001	Benign	0.002	Benign	2.56	Benign	0.00	Affected			-1	-1	-2.6	-30.09
c.3781A>G	S1261G 2D AIThe SynGAP1 missense variant S1261G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for S1261G, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250							-5.042	Likely Benign	0.087	Likely Benign	Likely Benign	0.063	Likely Benign	0.2063	0.3477											-0.46	Neutral	0.005	Benign	0.013	Benign	2.32	Pathogenic	0.65	Tolerated			1	0	0.4	-30.03
c.407G>C	R136P 2D AIThe SynGAP1 missense variant R136P is listed in ClinVar (ID 579340.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.433034	Structured	0.657394	Binding	0.351	0.894	0.250	Uncertain		1				-11.952	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.277	Likely Benign	0.2063	0.4426											-3.72	Deleterious	0.910	Possibly Damaging	0.578	Possibly Damaging	3.47	Benign	0.00	Affected	3.61	5	0	-2	2.9	-59.07
c.428G>C	R143P 2D AIThe SynGAP1 missense variant R143P is listed in gnomAD (ID 6‑33432725‑G‑C) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls come from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic.” Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not return a result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.575842	Disordered	0.538584	Binding	0.338	0.838	0.625				6-33432725-G-C	2	1.35e-6	-14.564	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.292	Likely Benign	0.2063	0.4457											-3.74	Deleterious	0.001	Benign	0.000	Benign	3.49	Benign	0.00	Affected	3.61	5	-2	0	2.9	-59.07
c.964G>C	A322P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A322P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, and SIFT, while pathogenic calls are made by SGM‑Consensus, Rosetta, Foldetta, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: FoldX and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Thus, the variant is most likely pathogenic, with no ClinVar evidence to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.175930	Structured	0.425745	Uncertain	0.938	0.334	0.000							-10.558	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous	0.343	Likely Benign	0.2064	0.5400		1.26	Ambiguous	1.3	5.43	Destabilizing	3.35	Destabilizing	0.40	Likely Benign	-1.72	Neutral	0.784	Possibly Damaging	0.390	Benign	1.90	Pathogenic	0.18	Tolerated			1	-1	-3.4	26.04
c.2116G>A	E706K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E706K is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM all classify the change as benign. In contrast, ESM1b and AlphaMissense‑Default predict a pathogenic impact. Tools that return uncertain results—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—do not provide decisive evidence. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign calls). High‑accuracy assessments are likewise ambiguous: AlphaMissense‑Optimized is uncertain, Foldetta is uncertain, and the SGM Consensus remains inconclusive. Overall, the preponderance of evidence points to a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000	Uncertain		1				-10.519	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	0.080	Likely Benign	0.2065	0.4511		1.17	Ambiguous	0.1	0.51	Ambiguous	0.84	Ambiguous	0.08	Likely Benign	-1.51	Neutral	0.345	Benign	0.028	Benign	4.15	Benign	0.52	Tolerated	3.47	10	0	1	-0.4	-0.94	187.1	49.2	0.0	0.0	0.4	0.1						X		Uncertain	The carboxylate side chain of Glu706, located at the end and outer surface of an α-helix (res. Thr704-Gly712), forms a salt bridge with Lys710 and a hydrogen bond with its own backbone amino group at the helix end in the WT simulations. Although Lys706 is unable to make these transient interactions in the variant simulations, there is no apparent negative effect on the protein structure due to the residue swap. However, because the model ends abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2568C>A	N856K 2D AIThe SynGAP1 missense variant N856K 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 majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for N856K, and this conclusion is not in conflict with any ClinVar annotation, as none exists. 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							-3.511	Likely Benign	0.429	Ambiguous	Likely Benign	0.079	Likely Benign	0.2065	0.6252											-1.51	Neutral	0.965	Probably Damaging	0.721	Possibly Damaging	4.19	Benign	0.26	Tolerated			1	0	-0.4	14.07
c.2568C>G	N856K 2D AIThe SynGAP1 missense variant N856K 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 majority of high‑accuracy predictors—AlphaMissense‑Optimized and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for N856K, and 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		0.637480	Disordered	0.477615	Uncertain	0.263	0.827	0.500							-3.511	Likely Benign	0.429	Ambiguous	Likely Benign	0.079	Likely Benign	0.2065	0.6252											-1.51	Neutral	0.965	Probably Damaging	0.721	Possibly Damaging	4.19	Benign	0.26	Tolerated			1	0	-0.4	14.07
c.3948T>A	N1316K 2D AIThe SynGAP1 missense variant N1316K is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451822‑T‑A). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750				6-33451822-T-A			-3.815	Likely Benign	0.699	Likely Pathogenic	Likely Benign	0.044	Likely Benign	0.2065	0.5500											-3.27	Deleterious	0.414	Benign	0.063	Benign	4.00	Benign	0.00	Affected	3.77	5	0	1	-0.4	14.07
c.3948T>G	N1316K 2D AIThe SynGAP1 missense variant N1316K is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451822‑T‑G). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign + 2 pathogenic), 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 is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750				6-33451822-T-G			-3.815	Likely Benign	0.699	Likely Pathogenic	Likely Benign	0.044	Likely Benign	0.2065	0.5500											-3.27	Deleterious	0.414	Benign	0.063	Benign	4.00	Benign	0.00	Affected	3.77	5	0	1	-0.4	14.07
c.4013G>C	R1338P 2D AISynGAP1 missense variant R1338P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the available predictions are evenly split between benign and pathogenic, with no high‑accuracy tool providing definitive support. Therefore, the variant is most likely pathogenic based on the balance of evidence, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000							-3.678	Likely Benign	0.954	Likely Pathogenic	Ambiguous	0.191	Likely Benign	0.2065	0.5095											-3.43	Deleterious	0.931	Possibly Damaging	0.410	Benign	3.75	Benign	0.01	Affected			0	-2	2.9	-59.07
c.1432G>A	E478K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478K is not reported in ClinVar (ClinVar ID: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus (Likely Pathogenic), PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as benign. Overall, the majority of evidence (eight benign versus five pathogenic predictions) points to a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000							-12.654	Likely Pathogenic	0.899	Likely Pathogenic	Ambiguous	0.309	Likely Benign	0.2066	0.6192		0.23	Likely Benign	0.0	0.12	Likely Benign	0.18	Likely Benign	-0.02	Likely Benign	-3.45	Deleterious	0.320	Benign	0.117	Benign	3.49	Benign	0.05	Affected			0	1	-0.4	-0.94
c.3353G>C	S1118T 2D AIThe SynGAP1 missense variant S1118T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts 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 Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750							-6.063	Likely Benign	0.067	Likely Benign	Likely Benign	0.196	Likely Benign	0.2066	0.5587											-0.67	Neutral	0.790	Possibly Damaging	0.433	Benign	5.18	Benign	0.10	Tolerated			1	1	0.1	14.03
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	0.2066	0.2614											-4.84	Deleterious	0.991	Probably Damaging	0.982	Probably Damaging	2.09	Pathogenic	0.00	Affected			0	-1	3.2	-27.07
c.4013G>T	R1338L 2D AIThe SynGAP1 missense variant R1338L is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451887‑G‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.977425	Binding	0.393	0.697	1.000				6-33451887-G-T			-3.359	Likely Benign	0.587	Likely Pathogenic	Likely Benign	0.232	Likely Benign	0.2066	0.5307											-3.65	Deleterious	0.001	Benign	0.001	Benign	3.78	Benign	0.01	Affected	3.77	5	-2	-3	8.3	-43.03
c.651G>C	E217D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E217D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign. The only inconclusive result comes from AlphaMissense‑Default, which is listed as uncertain. High‑accuracy assessments corroborate this benign profile: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a benign outcome. No pathogenic predictions are present. Therefore, based on the available computational evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.278302	Structured	0.404912	Uncertain	0.823	0.284	0.000							-2.268	Likely Benign	0.453	Ambiguous	Likely Benign	0.276	Likely Benign	0.2066	0.5976		0.24	Likely Benign	0.3	-0.07	Likely Benign	0.09	Likely Benign	-0.34	Likely Benign	0.66	Neutral	0.014	Benign	0.007	Benign	5.85	Benign	0.85	Tolerated	3.41	13	2	3	0.0	-14.03
c.651G>T	E217D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E217D is present in gnomAD (6‑33435293‑G‑T) but has no ClinVar entry. Functional prediction tools uniformly classify it as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and Foldetta all report benign or benign‑like outcomes. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized indicates 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, also reports benign. AlphaMissense‑Default remains uncertain and is treated as unavailable. Overall, the evidence strongly supports a benign effect for E217D, 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	PH	0.278302	Structured	0.404912	Uncertain	0.823	0.284	0.000				6-33435293-G-T	1	6.20e-7	-2.268	Likely Benign	0.453	Ambiguous	Likely Benign	0.276	Likely Benign	0.2066	0.5976		0.24	Likely Benign	0.3	-0.07	Likely Benign	0.09	Likely Benign	-0.34	Likely Benign	0.66	Neutral	0.014	Benign	0.007	Benign	5.85	Benign	0.85	Tolerated	3.41	13	2	3	0.0	-14.03
c.695C>A	A232D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A232D 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, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Uncertain or inconclusive results are reported for Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as pathogenic, while Foldetta remains uncertain. Overall, the majority of available predictions support a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.307228	Uncertain	0.878	0.305	0.000							-13.956	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.725	Likely Pathogenic	0.2066	0.2896		0.14	Likely Benign	0.2	1.55	Ambiguous	0.85	Ambiguous	0.77	Ambiguous	-2.50	Deleterious	0.845	Possibly Damaging	0.348	Benign	5.78	Benign	0.02	Affected			0	-2	-5.3	44.01
c.466T>C	F156L 2D AIThe SynGAP1 missense variant F156L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus is ambiguous. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500							-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic	0.180	Likely Benign	0.2067	0.3109											-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			2	0	1.0	-34.02
c.468T>A	F156L 2D AIThe SynGAP1 missense variant F156L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus is ambiguous. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500							-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic	0.164	Likely Benign	0.2067	0.3109											-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			2	0	1.0	-34.02
c.468T>G	F156L 2D AISynGAP1 missense variant F156L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (benign)—leans toward benign. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of conventional tools indicates a pathogenic effect, and the high‑accuracy predictions are mixed; no ClinVar entry exists to contradict the assessment. Therefore, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500							-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic	0.163	Likely Benign	0.2067	0.3109											-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			2	0	1.0	-34.02
c.1112G>A	S371N 2D AIThe SynGAP1 missense variant S371N is not reported in ClinVar and is absent from gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments are consistent: AlphaMissense‑Optimized classifies the variant as benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375							-5.950	Likely Benign	0.160	Likely Benign	Likely Benign	0.208	Likely Benign	0.2068	0.5100		0.21	Likely Benign	0.8	-0.59	Ambiguous	-0.19	Likely Benign	0.25	Likely Benign	-0.31	Neutral	0.666	Possibly Damaging	0.067	Benign	4.64	Benign	0.27	Tolerated			1	1	-2.7	27.03
c.364C>A	P122T 2D AIThe SynGAP1 missense variant P122T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that P122T 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		0.618285	Disordered	0.672358	Binding	0.400	0.887	0.750							-3.954	Likely Benign	0.088	Likely Benign	Likely Benign	0.186	Likely Benign	0.2068	0.5270											-1.43	Neutral	0.580	Possibly Damaging	0.185	Benign	4.19	Benign	0.13	Tolerated			0	-1	0.9	3.99
c.3242C>A	A1081D 2D AIThe SynGAP1 missense variant A1081D is not 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 the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is Uncertain, and the Foldetta protein‑folding stability assessment is unavailable. 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		0.874069	Disordered	0.979759	Binding	0.288	0.895	0.750							-4.603	Likely Benign	0.892	Likely Pathogenic	Ambiguous	0.095	Likely Benign	0.2069	0.2600											-1.84	Neutral	0.611	Possibly Damaging	0.404	Benign	3.97	Benign	0.04	Affected			0	-2	-5.3	44.01
c.3856G>A	E1286K 2D AIThe SynGAP1 missense variant E1286K is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33447904‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, 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 predicts benign. Foldetta results are unavailable. Overall, the majority of evidence (5 benign vs. 3 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet classified there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.817022	Binding	0.544	0.765	0.750				6-33447904-G-A			-3.784	Likely Benign	0.395	Ambiguous	Likely Benign	0.195	Likely Benign	0.2069	0.5117											-2.36	Neutral	0.770	Possibly Damaging	0.242	Benign	2.47	Pathogenic	0.02	Affected	3.77	5	1	0	-0.4	-0.94
c.824C>A	P275H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P275H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which classify the change as pathogenic. Tools that are inconclusive or uncertain are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Taken together, the majority of evidence points to a pathogenic impact, and this conclusion is consistent with the lack of ClinVar annotation (no contradiction). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.059222	Structured	0.353469	Uncertain	0.811	0.208	0.250							-13.157	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous	0.585	Likely Pathogenic	0.2069	0.3074		2.34	Destabilizing	0.8	0.87	Ambiguous	1.61	Ambiguous	0.88	Ambiguous	-6.54	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.73	Pathogenic	0.01	Affected			0	-2	-1.6	40.02
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	0.545	Likely Pathogenic	0.2070	0.1755		4.32	Destabilizing	0.3	0.47	Likely Benign	2.40	Destabilizing	1.44	Destabilizing	-5.98	Deleterious	0.994	Probably Damaging	0.659	Possibly Damaging	3.08	Benign	0.01	Affected			1	0	1.7	-34.02
c.368C>G	A123G 2D AIThe SynGAP1 missense variant A123G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, 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		0.521092	Disordered	0.689505	Binding	0.324	0.886	0.750							-2.799	Likely Benign	0.121	Likely Benign	Likely Benign	0.065	Likely Benign	0.2070	0.5039											-1.34	Neutral	0.421	Benign	0.074	Benign	4.13	Benign	0.03	Affected			1	0	-2.2	-14.03
c.3923G>C	R1308P 2D AIThe SynGAP1 missense variant R1308P is not reported in ClinVar but is present in gnomAD (ID 6‑33451797‑G‑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 a 2‑vs‑2 split and therefore inconclusive. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Because the available predictions are evenly divided between benign and pathogenic, the overall computational assessment is inconclusive; the variant is neither clearly benign nor clearly pathogenic. This lack of consensus does not contradict ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.741537	Disordered	0.930652	Binding	0.378	0.904	0.750				6-33451797-G-C			-1.320	Likely Benign	0.216	Likely Benign	Likely Benign	0.158	Likely Benign	0.2070	0.5020											-4.62	Deleterious	0.995	Probably Damaging	0.992	Probably Damaging	2.32	Pathogenic	0.00	Affected	3.77	5	-2	0	2.9	-59.07
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	0.439	Likely Benign	0.2071	0.2235		2.06	Destabilizing	0.5	2.15	Destabilizing	2.11	Destabilizing	0.53	Ambiguous	-0.93	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.04	Affected	4.32	2	-1	1	-3.1	58.04
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	0.203	Likely Benign	0.2071	0.4650		-0.40	Likely Benign	0.2	0.35	Likely Benign	-0.03	Likely Benign	0.47	Likely Benign	-3.81	Deleterious	0.993	Probably Damaging	0.993	Probably Damaging	3.32	Benign	0.05	Affected	3.37	35	-1	1	-0.8	10.04
c.896G>C	R299P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R299P is not reported in ClinVar or gnomAD, indicating no publicly available frequency data. Prediction tools cluster into benign and pathogenic groups: benign predictions include REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, SIFT, FATHMM, and AlphaMissense‑Default; ESM1b is uncertain. The SGM‑Consensus label is Likely Pathogenic. High‑accuracy tools give a clear signal: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta also predicts pathogenic. Overall, the predictions strongly favor a pathogenic interpretation, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.262979	Uncertain	0.819	0.295	0.500							-7.662	In-Between	0.722	Likely Pathogenic	Likely Benign	0.295	Likely Benign	0.2072	0.5379		4.10	Destabilizing	0.2	3.01	Destabilizing	3.56	Destabilizing	1.19	Destabilizing	-4.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.68	Pathogenic	0.02	Affected			0	-2	2.9	-59.07
c.1490A>T	Y497F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497F is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, ESM1b, and FATHMM; premPS 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 predictions lean toward a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on the current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.393608	Uncertain	0.950	0.181	0.000							-8.566	Likely Pathogenic	0.199	Likely Benign	Likely Benign	0.578	Likely Pathogenic	0.2074	0.2242		-0.27	Likely Benign	0.1	0.47	Likely Benign	0.10	Likely Benign	0.61	Ambiguous	-3.75	Deleterious	0.367	Benign	0.131	Benign	-1.15	Pathogenic	0.19	Tolerated			7	3	4.1	-16.00
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	0.560	Likely Pathogenic	0.2074	0.1583		4.17	Destabilizing	0.1	1.18	Ambiguous	2.68	Destabilizing	1.47	Destabilizing	-6.97	Deleterious	0.992	Probably Damaging	0.756	Possibly Damaging	3.08	Benign	0.02	Affected			-1	-1	1.4	-48.04
c.2798A>G	H933R 2D AIThe SynGAP1 missense variant H933R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and AlphaMissense‑Optimized, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625							-4.410	Likely Benign	0.650	Likely Pathogenic	Likely Benign	0.393	Likely Benign	0.2074	0.2922											-3.84	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.43	Pathogenic	0.06	Tolerated			2	0	-1.3	19.05
c.27T>A	H9Q 2D AIThe SynGAP1 missense variant H9Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750							-3.477	Likely Benign	0.117	Likely Benign	Likely Benign	0.069	Likely Benign	0.2074	0.4297											-0.05	Neutral	0.000	Benign	0.000	Benign	4.24	Benign	0.00	Affected			3	0	-0.3	-9.01
c.27T>G	H9Q 2D AIThe SynGAP1 missense variant H9Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750							-3.477	Likely Benign	0.117	Likely Benign	Likely Benign	0.071	Likely Benign	0.2074	0.4297											-0.05	Neutral	0.000	Benign	0.000	Benign	4.24	Benign	0.00	Affected			3	0	-0.3	-9.01
c.2881C>A	H961N 2D AIThe SynGAP1 missense variant H961N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that H961N 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		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750							-8.561	Likely Pathogenic	0.096	Likely Benign	Likely Benign	0.084	Likely Benign	0.2074	0.3695											-0.32	Neutral	0.069	Benign	0.036	Benign	4.17	Benign	0.81	Tolerated			2	1	-0.3	-23.04
c.524A>C	Q175P 2D AIThe SynGAP1 missense variant Q175P is reported in gnomAD (ID 6‑33435166‑A‑C) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the substitution as benign. The consensus from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely benign. High‑accuracy predictors corroborate this assessment: AlphaMissense‑Optimized predicts a benign outcome, and the SGM‑Consensus (majority vote) confirms a likely benign status. No high‑accuracy folding‑stability analysis (Foldetta) is available for this residue, so stability effects remain unassessed. Overall, the collective evidence points to a benign impact for Q175P, and this conclusion is consistent with the absence of a pathogenic ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375				6-33435166-A-C	1	6.20e-7	-6.995	Likely Benign	0.432	Ambiguous	Likely Benign	0.211	Likely Benign	0.2075	0.4584											1.55	Neutral	0.396	Benign	0.188	Benign	4.20	Benign	1.00	Tolerated	3.61	5	-1	0	1.9	-31.01
c.1508A>C	Q503P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q503P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; the remaining tools (FoldX, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenic. Because the majority of evidence points to a deleterious effect, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.322935	Uncertain	0.848	0.168	0.000							-10.915	Likely Pathogenic	0.414	Ambiguous	Likely Benign	0.860	Likely Pathogenic	0.2076	0.3610		1.06	Ambiguous	0.7	5.94	Destabilizing	3.50	Destabilizing	0.75	Ambiguous	-5.20	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	-1.53	Pathogenic	0.03	Affected			0	-1	1.9	-31.01
c.3011A>C	H1004P 2D AIThe SynGAP1 missense variant H1004P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and the high‑accuracy AlphaMissense‑Optimized model. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign majority vote. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction between the predictions and ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750							-3.686	Likely Benign	0.460	Ambiguous	Likely Benign	0.236	Likely Benign	0.2076	0.4643											-2.69	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.72	Benign	0.18	Tolerated			0	-2	1.6	-40.02
c.3022G>A	D1008N 2D AIThe SynGAP1 missense variant D1008N is listed in ClinVar (ID 1213097.0) as benign and is present in gnomAD (variant ID 6‑33443574‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, a majority‑vote model of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of evidence indicates a benign effect, consistent with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625	Likely Benign		1	6-33443574-G-A	3	1.86e-6	-4.045	Likely Benign	0.714	Likely Pathogenic	Likely Benign	0.128	Likely Benign	0.2076	0.7013											-2.15	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.75	Benign	0.01	Affected	3.77	5	2	1	0.0	-0.98
c.86T>G	M29R 2D AIThe SynGAP1 missense variant M29R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, 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		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250							-1.708	Likely Benign	0.241	Likely Benign	Likely Benign	0.211	Likely Benign	0.2076	0.1293											-0.92	Neutral	0.042	Benign	0.184	Benign	4.23	Benign	0.00	Affected			0	-1	-6.4	24.99
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	0.528	Likely Pathogenic	0.2077	0.1645		3.30	Destabilizing	1.4	-1.00	Ambiguous	1.15	Ambiguous	0.57	Ambiguous	-2.60	Deleterious	0.991	Probably Damaging	0.831	Possibly Damaging	1.32	Pathogenic	0.19	Tolerated			1	-1	-3.1	58.04
c.3027G>C	E1009D 2D AIThe SynGAP1 missense variant E1009D is reported in gnomAD (ID 6‑33443579‑G‑C) but has no ClinVar entry. All in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized indicates benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign effect, 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		0.728858	Disordered	0.914552	Binding	0.325	0.885	0.500				6-33443579-G-C	1	6.20e-7	-2.958	Likely Benign	0.104	Likely Benign	Likely Benign	0.054	Likely Benign	0.2077	0.4817											-0.37	Neutral	0.011	Benign	0.017	Benign	2.50	Benign	0.30	Tolerated	3.77	5	2	3	0.0	-14.03
c.3027G>T	E1009D 2D AIThe SynGAP1 missense variant E1009D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.914552	Binding	0.325	0.885	0.500							-2.958	Likely Benign	0.104	Likely Benign	Likely Benign	0.054	Likely Benign	0.2077	0.4817											-0.37	Neutral	0.011	Benign	0.017	Benign	2.50	Benign	0.30	Tolerated	3.77	5	2	3	0.0	-14.03
c.3059G>C	R1020P 2D AIThe SynGAP1 missense variant R1020P is listed in ClinVar (ID 3700393.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Pathogenic” (3 pathogenic vs. 1 benign votes). High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500	Uncertain		1				-3.491	Likely Benign	0.902	Likely Pathogenic	Ambiguous	0.205	Likely Benign	0.2077	0.5109											-3.50	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.46	Pathogenic	0.00	Affected			0	-2	2.9	-59.07
c.2396C>T	P799L 2D AIThe SynGAP1 missense variant P799L is not 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 P799L, 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	0.537892	Binding	0.400	0.894	0.750							-5.296	Likely Benign	0.090	Likely Benign	Likely Benign	0.043	Likely Benign	0.2078	0.6285											-0.93	Neutral	0.905	Possibly Damaging	0.670	Possibly Damaging	4.27	Benign	0.00	Affected			-3	-3	5.4	16.04
c.3704T>C	M1235T 2D AIThe SynGAP1 missense variant M1235T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign impact. This prediction does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125							-5.381	Likely Benign	0.149	Likely Benign	Likely Benign	0.060	Likely Benign	0.2079	0.1814											-2.39	Neutral	0.425	Benign	0.158	Benign	2.66	Benign	0.01	Affected			-1	-1	-2.6	-30.09
c.1724G>C	R575P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R575P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only SIFT, whereas all other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Based on the overwhelming consensus of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for R575P. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000							-16.008	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.774	Likely Pathogenic	0.2080	0.2670		3.50	Destabilizing	0.1	4.97	Destabilizing	4.24	Destabilizing	1.13	Destabilizing	-3.69	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.33	Pathogenic	0.10	Tolerated			0	-2	2.9	-59.07
c.2078A>C	H693P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, which classifies the variant as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000							-16.281	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.600	Likely Pathogenic	0.2080	0.3210		5.54	Destabilizing	0.2	6.09	Destabilizing	5.82	Destabilizing	1.06	Destabilizing	-9.97	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.09	Benign	0.01	Affected			0	-2	1.6	-40.02
c.3424T>C	S1142P 2D AIThe SynGAP1 missense variant S1142P is listed in ClinVar (ID 2747352.0) as Benign and is present in gnomAD (variant ID 6‑33444459‑T‑C). 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, 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 not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.719935	Binding	0.276	0.844	1.000	Likely Benign		1	6-33444459-T-C	1	6.20e-7	-2.713	Likely Benign	0.222	Likely Benign	Likely Benign	0.107	Likely Benign	0.2080	0.5618											-2.19	Neutral	0.918	Possibly Damaging	0.761	Possibly Damaging	2.64	Benign	0.00	Affected	4.32	4	-1	1	-0.8	10.04
c.2209C>A	Q737K 2D AIThe SynGAP1 missense variant Q737K is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign 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. Taken together, the majority of evidence points to a benign effect for Q737K, and this conclusion is not in conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.425743	Uncertain	0.323	0.803	0.875							-5.841	Likely Benign	0.190	Likely Benign	Likely Benign	0.053	Likely Benign	0.2081	0.4009											-1.16	Neutral	0.906	Possibly Damaging	0.551	Possibly Damaging	2.77	Benign	0.07	Tolerated			1	1	-0.4	0.04
c.2958G>C	E986D 2D AIThe SynGAP1 missense variant E986D is not 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, FATHMM, 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 (two pathogenic vs two benign votes) and Foldetta results are unavailable. Overall, the majority of conventional tools lean toward pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus leave the variant’s impact uncertain. There is no contradiction 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.			0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750							-4.001	Likely Benign	0.628	Likely Pathogenic	Likely Benign	0.129	Likely Benign	0.2081	0.5364											-1.22	Neutral	0.974	Probably Damaging	0.715	Possibly Damaging	2.32	Pathogenic	0.00	Affected			3	2	0.0	-14.03
c.2958G>T	E986D 2D AIThe SynGAP1 missense variant E986D is not 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, FATHMM, 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 (two pathogenic vs two benign votes) and Foldetta results are unavailable. Overall, the majority of conventional tools lean toward pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus leave the variant’s impact uncertain. There is no contradiction 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.			0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750							-4.001	Likely Benign	0.628	Likely Pathogenic	Likely Benign	0.129	Likely Benign	0.2081	0.5364											-1.22	Neutral	0.974	Probably Damaging	0.715	Possibly Damaging	2.32	Pathogenic	0.00	Affected			3	2	0.0	-14.03
c.3394T>C	S1132P 2D AIThe SynGAP1 missense variant S1132P is listed in ClinVar with an uncertain significance (ClinVar ID 1341927.0) and is present in the gnomAD database (gnomAD ID 6‑33443946‑T‑C). All available in‑silico predictors uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or likely benign outcomes. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports a benign effect, which is consistent with the ClinVar uncertain classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.845506	Binding	0.289	0.894	0.750	Conflicting		3	6-33443946-T-C	1	6.74e-7	-1.423	Likely Benign	0.144	Likely Benign	Likely Benign	0.301	Likely Benign	0.2081	0.5700											0.38	Neutral	0.003	Benign	0.006	Benign	5.40	Benign	0.28	Tolerated	4.32	4	1	-1	-0.8	10.04
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	0.2081	0.2857											-3.00	Deleterious	0.989	Probably Damaging	0.621	Possibly Damaging	3.91	Benign	0.02	Affected			1	0	-2.2	-14.03
c.71T>G	V24G 2D AIThe SynGAP1 missense variant V24G is not reported in ClinVar (ClinVar status: not present) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.438970	Uncertain	0.382	0.890	0.500							-2.673	Likely Benign	0.256	Likely Benign	Likely Benign	0.178	Likely Benign	0.2081	0.3105											-1.67	Neutral	0.026	Benign	0.049	Benign	3.77	Benign	0.00	Affected			-1	-3	-4.6	-42.08
c.2737A>C	T913P 2D AIThe SynGAP1 missense variant T913P 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. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. 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 points to a benign impact for T913P, 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		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375							-2.029	Likely Benign	0.117	Likely Benign	Likely Benign	0.176	Likely Benign	0.2082	0.5786											-1.43	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.26	Tolerated			0	-1	-0.9	-3.99
c.3433A>G	N1145D 2D AIThe SynGAP1 missense variant N1145D 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 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 status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.722723	Binding	0.284	0.850	1.000							-3.053	Likely Benign	0.682	Likely Pathogenic	Likely Benign	0.332	Likely Benign	0.2082	0.3956											-2.04	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.57	Benign	0.08	Tolerated			2	1	0.0	0.98
c.233G>C	R78P 2D AIThe SynGAP1 missense variant R78P is 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, REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for R78P, 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 Benign		0.505461	Disordered	0.448183	Uncertain	0.304	0.866	0.500							-4.049	Likely Benign	0.611	Likely Pathogenic	Likely Benign	0.115	Likely Benign	0.2083	0.3750											-1.72	Neutral	0.817	Possibly Damaging	0.123	Benign	3.82	Benign	0.00	Affected			0	-2	2.9	-59.07
c.3004C>A	H1002N 2D AIThe SynGAP1 missense variant H1002N 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. High‑accuracy methods reinforce the benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no Foldetta data to contradict. Overall, the preponderance of evidence points to a benign effect for H1002N, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500							-5.622	Likely Benign	0.466	Ambiguous	Likely Benign	0.076	Likely Benign	0.2084	0.3057											-1.41	Neutral	0.801	Possibly Damaging	0.596	Possibly Damaging	2.76	Benign	1.00	Tolerated			2	1	-0.3	-23.04
c.2081C>A	A694D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A694D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, FATHMM, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are premPS, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the variant’s functional impact remains ambiguous. The predictions do not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000							-9.542	Likely Pathogenic	0.841	Likely Pathogenic	Ambiguous	0.163	Likely Benign	0.2085	0.2216		0.35	Likely Benign	0.1	1.04	Ambiguous	0.70	Ambiguous	1.01	Destabilizing	-2.47	Neutral	0.918	Possibly Damaging	0.375	Benign	3.48	Benign	0.05	Affected			0	-2	-5.3	44.01
c.2834A>T	H945L 2D AIThe SynGAP1 missense variant H945L is reported in gnomAD (ID 6‑33443386‑A‑T) 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, and the SGM‑Consensus (majority vote of 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 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 is consistent with the absence of a pathogenic ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.982235	Disordered	0.849210	Binding	0.386	0.923	0.750				6-33443386-A-T	2	1.24e-6	-4.741	Likely Benign	0.088	Likely Benign	Likely Benign	0.399	Likely Benign	0.2085	0.4526											0.16	Neutral	0.948	Possibly Damaging	0.863	Possibly Damaging	5.05	Benign	1.00	Tolerated	4.32	4	-3	-2	7.0	-23.98
c.2338T>C	S780P 2D AIThe SynGAP1 missense variant S780P is reported in gnomAD (ID 6‑33442890‑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. 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, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.812415	Binding	0.283	0.883	0.500				6-33442890-T-C	1	6.22e-7	-6.055	Likely Benign	0.234	Likely Benign	Likely Benign	0.088	Likely Benign	0.2086	0.6171											-1.11	Neutral	0.995	Probably Damaging	0.892	Possibly Damaging	2.64	Benign	0.30	Tolerated	3.64	6	-1	1	-0.8	10.04
c.4015A>G	N1339D 2D AIThe SynGAP1 missense variant N1339D is catalogued in gnomAD (ID 6‑33451889‑A‑G) but has no ClinVar submission. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. When aggregated into a consensus, the four contributing scores (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) split evenly, leaving the SGM Consensus inconclusive. High‑accuracy assessments further indicate a benign outcome from AlphaMissense‑Optimized; the SGM Consensus and Foldetta predictions are unavailable. Overall, the majority of individual tools predict pathogenicity, and the high‑accuracy benign prediction does not overturn this trend. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.771762	Disordered	0.977585	Binding	0.396	0.687	1.000				6-33451889-A-G			-2.533	Likely Benign	0.634	Likely Pathogenic	Likely Benign	0.186	Likely Benign	0.2087	0.4721											-3.04	Deleterious	0.980	Probably Damaging	0.956	Probably Damaging	2.92	Benign	0.00	Affected	3.77	5	1	2	0.0	0.98
c.769A>G	S257G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S257G is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD status: None). Prediction tools that agree on a benign effect include SIFT, FATHMM, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates a benign change, whereas the SGM‑Consensus (majority vote) indicates likely pathogenic. The Foldetta stability prediction is unavailable and therefore does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the lack of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.258293	Uncertain	0.847	0.272	0.250							-11.206	Likely Pathogenic	0.624	Likely Pathogenic	Likely Benign	0.703	Likely Pathogenic	0.2087	0.3589		0.61	Ambiguous	0.3	0.60	Ambiguous	0.61	Ambiguous	0.62	Ambiguous	-2.95	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	5.79	Benign	0.11	Tolerated			1	0	0.4	-30.03
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	0.183	Likely Benign	0.2088	0.1824		0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			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	0.182	Likely Benign	0.2088	0.1824		0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			3	2	0.0	-14.03
c.1900G>C	A634P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a deleterious effect: benign predictions are limited to 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 reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding 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, as none is available. 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							-15.372	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.745	Likely Pathogenic	0.2090	0.3429		4.17	Destabilizing	0.2	7.72	Destabilizing	5.95	Destabilizing	1.39	Destabilizing	-4.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.50	Benign	0.01	Affected			1	-1	-3.4	26.04
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	0.462	Likely Benign	0.2090	0.1963		3.23	Destabilizing	0.1	3.04	Destabilizing	3.14	Destabilizing	2.12	Destabilizing	-2.78	Deleterious	0.994	Probably Damaging	0.790	Possibly Damaging	3.17	Benign	0.00	Affected			-2	-2	-7.3	14.97
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	0.2090	0.0545											-1.14	Neutral	0.990	Probably Damaging	0.900	Possibly Damaging	3.88	Benign	0.00	Affected			-2	-2	-2.2	-49.07
c.1708G>T	A570S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570S is not 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. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The remaining tools (FoldX, Rosetta, Foldetta, premPS, and ESM1b) yield 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, and PROVEAN) also favors benign, while Foldetta remains uncertain. Overall, the majority of reliable predictions indicate 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	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000							-7.893	In-Between	0.194	Likely Benign	Likely Benign	0.399	Likely Benign	0.2091	0.3256		0.77	Ambiguous	0.1	1.68	Ambiguous	1.23	Ambiguous	0.51	Ambiguous	-2.26	Neutral	0.983	Probably Damaging	0.993	Probably Damaging	-1.19	Pathogenic	0.17	Tolerated			1	1	-2.6	16.00
c.1991T>C	L664S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664S is listed in ClinVar as Benign (ClinVar ID 2429773.0) and is present in gnomAD (ID 6‑33441250‑T‑C). Prediction tools that report a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Based on the overwhelming majority of pathogenic predictions—including the high‑accuracy tools—the variant is most likely pathogenic, which contradicts its ClinVar benign classification. 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	Likely Benign		1	6-33441250-T-C	1	6.20e-7	-16.498	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.543	Likely Pathogenic	0.2091	0.0896		3.75	Destabilizing	0.2	3.63	Destabilizing	3.69	Destabilizing	2.77	Destabilizing	-5.99	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.85	Benign	0.00	Affected	3.38	28	-3	-2	-4.6	-26.08	215.5	50.1	0.0	0.0	-0.2	0.2						X		Potentially Benign	The iso-butyl side chain of L664, located on an α-helix (res. Ser641-Glu666), hydrophobically interacts with residues in the inter-helix space between three helices (res. Glu617-Asn635, res. Glu582-Met603, and res. Ser641-Glu666), such as Ile589, Phe663, and Met660. In the variant simulations, the hydroxyl group of Ser664 forms hydrogen bonds with the backbone carbonyl oxygen of another helix residue, such as Met660 or Gln661. This interaction is known to destabilize hydrogen bonding in the α-helix, but this effect was not observed in the simulations. Additionally, Ser664 occasionally forms hydrogen bonds with the carboxylate group of Asp586 on another α-helix (res. Glu582-Met603), which could minimally influence the tertiary structure assembly. Despite these interactions, no major negative effects on the protein structure were observed during the simulations.
c.2604C>A	D868E 2D AIThe SynGAP1 missense variant D868E 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 of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic claim. Thus, 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		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250							-3.792	Likely Benign	0.270	Likely Benign	Likely Benign	0.064	Likely Benign	0.2092	0.6392											-1.47	Neutral	0.966	Probably Damaging	0.848	Possibly Damaging	2.68	Benign	0.36	Tolerated			3	2	0.0	14.03
c.2604C>G	D868E 2D AIThe SynGAP1 missense variant D868E 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 assessments 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 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		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250							-3.792	Likely Benign	0.270	Likely Benign	Likely Benign	0.063	Likely Benign	0.2092	0.6392											-1.47	Neutral	0.966	Probably Damaging	0.848	Possibly Damaging	2.68	Benign	0.36	Tolerated			3	2	0.0	14.03
c.109T>A	S37T 2D AIThe SynGAP1 missense variant S37T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumVar and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500							-3.854	Likely Benign	0.134	Likely Benign	Likely Benign	0.062	Likely Benign	0.2093	0.5974											-0.60	Neutral	0.140	Benign	0.481	Possibly Damaging	3.95	Benign	0.00	Affected			1	1	0.1	14.03
c.16G>C	A6P 2D AIThe SynGAP1 missense variant A6P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.566480	Disordered	0.549054	Binding	0.377	0.920	0.875							-3.440	Likely Benign	0.090	Likely Benign	Likely Benign	0.148	Likely Benign	0.2093	0.5007											-0.12	Neutral	0.000	Benign	0.000	Benign	4.06	Benign	0.00	Affected			1	-1	-3.4	26.04
c.3592T>A	Y1198N 2D AIThe SynGAP1 missense variant Y1198N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is “Likely Pathogenic,” and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250							-13.134	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.282	Likely Benign	0.2093	0.0373											-5.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.44	Pathogenic	0.26	Tolerated			-2	-2	-2.2	-49.07
c.3662G>A	R1221Q 2D AIThe SynGAP1 missense variant R1221Q is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33446654‑G‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, SGM Consensus is likely benign, while 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, 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	Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375	Conflicting		2	6-33446654-G-A	4	2.48e-6	-5.491	Likely Benign	0.115	Likely Benign	Likely Benign	0.078	Likely Benign	0.2093	0.1736											-1.46	Neutral	0.836	Possibly Damaging	0.153	Benign	2.56	Benign	0.12	Tolerated	3.77	5	1	1	1.0	-28.06
c.392G>A	G131D 2D AIThe SynGAP1 missense variant G131D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Two tools (ESM1b and AlphaMissense‑Optimized) return uncertain results. 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 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 (four pathogenic, three benign, two uncertain) leans toward pathogenicity. This prediction does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.724779	Binding	0.302	0.891	0.250							-7.477	In-Between	0.950	Likely Pathogenic	Ambiguous	0.180	Likely Benign	0.2093	0.2550											-3.29	Deleterious	0.888	Possibly Damaging	0.435	Benign	3.92	Benign	0.02	Affected			1	-1	-3.1	58.04
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	0.801	Likely Pathogenic	0.2094	0.1950		3.47	Destabilizing	0.1	3.10	Destabilizing	3.29	Destabilizing	1.84	Destabilizing	-3.85	Deleterious	0.994	Probably Damaging	0.985	Probably Damaging	-1.31	Pathogenic	0.01	Affected	3.37	31	-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.1676G>A	C559Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C559Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Because the evidence is split evenly between benign and pathogenic predictions and the high‑accuracy tools disagree, the variant is best classified as of uncertain significance. This assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.016021	Structured	0.010460	Uncertain	0.842	0.204	0.000							-11.767	Likely Pathogenic	0.868	Likely Pathogenic	Ambiguous	0.561	Likely Pathogenic	0.2094	0.2135		-0.37	Likely Benign	0.0	-0.19	Likely Benign	-0.28	Likely Benign	0.36	Likely Benign	-8.39	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.45	Benign	0.10	Tolerated			0	-2	-3.8	60.04
c.2825C>T	P942L 2D AIThe SynGAP1 missense variant P942L is listed in ClinVar (ID 2851884.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443377‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” 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 is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.878102	Binding	0.365	0.915	0.625	Uncertain		1	6-33443377-C-T	4	2.48e-6	-5.063	Likely Benign	0.086	Likely Benign	Likely Benign	0.048	Likely Benign	0.2094	0.5507											-2.00	Neutral	0.411	Benign	0.239	Benign	2.37	Pathogenic	0.00	Affected	4.32	4	-3	-3	5.4	16.04
c.2887C>A	H963N 2D AIThe SynGAP1 missense variant H963N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only ESM1b predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta 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, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.983973	Binding	0.325	0.886	0.750							-8.274	Likely Pathogenic	0.099	Likely Benign	Likely Benign	0.089	Likely Benign	0.2094	0.3596											-0.21	Neutral	0.369	Benign	0.120	Benign	4.18	Benign	0.16	Tolerated			2	1	-0.3	-23.04
c.1385A>C	K462T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K462T missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125							-11.586	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.414	Likely Benign	0.2095	0.3257		0.55	Ambiguous	0.0	1.08	Ambiguous	0.82	Ambiguous	0.30	Likely Benign	-5.82	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.47	Benign	0.08	Tolerated			0	-1	3.2	-27.07
c.3946A>G	N1316D 2D AIThe SynGAP1 missense variant N1316D is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451820‑A‑G). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also leans toward benign, with two benign and one pathogenic prediction among the four considered. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.971970	Binding	0.380	0.885	0.750				6-33451820-A-G			-2.717	Likely Benign	0.364	Ambiguous	Likely Benign	0.057	Likely Benign	0.2095	0.3745											-2.80	Deleterious	0.225	Benign	0.084	Benign	3.96	Benign	0.00	Affected	3.77	5	1	2	0.0	0.98
c.2376A>C	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875							-3.746	Likely Benign	0.089	Likely Benign	Likely Benign	0.091	Likely Benign	0.2096	0.5376											-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			3	2	0.0	-14.03
c.2376A>T	E792D 2D AIThe SynGAP1 missense variant E792D is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise predicts likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.974374	Disordered	0.452261	Uncertain	0.352	0.896	0.875							-3.746	Likely Benign	0.089	Likely Benign	Likely Benign	0.091	Likely Benign	0.2096	0.5376											-1.06	Neutral	0.000	Benign	0.001	Benign	3.97	Benign	0.26	Tolerated			3	2	0.0	-14.03
c.3106C>A	Q1036K 2D AIThe SynGAP1 missense variant Q1036K is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.987955	Binding	0.275	0.765	0.625							-3.757	Likely Benign	0.646	Likely Pathogenic	Likely Benign	0.079	Likely Benign	0.2096	0.5220											-1.72	Neutral	0.011	Benign	0.005	Benign	2.58	Benign	0.05	Affected			1	1	-0.4	0.04
c.107A>C	H36P 2D AIThe SynGAP1 missense variant H36P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375							-2.285	Likely Benign	0.066	Likely Benign	Likely Benign	0.171	Likely Benign	0.2097	0.4723											-1.23	Neutral	0.182	Benign	0.046	Benign	4.16	Benign	0.00	Affected			0	-2	1.6	-40.02
c.3011A>G	H1004R 2D AIThe SynGAP1 missense variant H1004R is not 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 the variant as Likely Benign. 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, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750							-3.316	Likely Benign	0.813	Likely Pathogenic	Ambiguous	0.198	Likely Benign	0.2097	0.3132											-1.88	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.77	Benign	0.50	Tolerated			2	0	-1.3	19.05
c.1372A>C	T458P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T458P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b, and the SGM‑Consensus) all predict a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000							-13.547	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.557	Likely Pathogenic	0.2098	0.5395		3.05	Destabilizing	0.2	5.36	Destabilizing	4.21	Destabilizing	0.78	Ambiguous	-5.33	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.06	Tolerated			0	-1	-0.9	-3.99
c.2787C>A	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375							-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.182	Likely Benign	0.2098	0.6046											-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			1	0	-0.4	14.07
c.2787C>G	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375							-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.182	Likely Benign	0.2098	0.6046											-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			1	0	-0.4	14.07
c.3308G>T	R1103L 2D AIThe SynGAP1 missense variant R1103L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443860‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.945666	Disordered	0.957363	Binding	0.328	0.862	0.875	Uncertain		1	6-33443860-G-T			-2.330	Likely Benign	0.205	Likely Benign	Likely Benign	0.173	Likely Benign	0.2098	0.5181											-2.35	Neutral	0.002	Benign	0.005	Benign	2.44	Pathogenic	0.02	Affected	3.77	5	-3	-2	8.3	-43.03
c.2888A>C	H963P 2D AIThe SynGAP1 missense variant H963P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only ESM1b predicts a pathogenic outcome, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports benign, and the SGM Consensus also indicates Likely Benign; Foldetta data are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not in conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.983973	Binding	0.325	0.886	0.750							-8.158	Likely Pathogenic	0.074	Likely Benign	Likely Benign	0.223	Likely Benign	0.2101	0.4487											-1.10	Neutral	0.000	Benign	0.001	Benign	4.10	Benign	0.14	Tolerated			0	-2	1.6	-40.02
c.874G>C	A292P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292P is not reported in ClinVar and is absent from gnomAD. Prediction tools largely converge on a deleterious effect: only REVEL classifies it as benign, whereas FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a destabilizing, pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000							-16.897	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.471	Likely Benign	0.2101	0.5988		4.37	Destabilizing	0.3	9.80	Destabilizing	7.09	Destabilizing	1.23	Destabilizing	-4.60	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.67	Pathogenic	0.01	Affected			1	-1	-3.4	26.04
c.2833C>T	H945Y 2D AIThe SynGAP1 missense variant H945Y 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 result is available. Overall, the majority of evidence points to a benign effect for H945Y, 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		0.982235	Disordered	0.849210	Binding	0.386	0.923	0.750							-6.036	Likely Benign	0.112	Likely Benign	Likely Benign	0.335	Likely Benign	0.2102	0.3912											-0.07	Neutral	0.982	Probably Damaging	0.903	Possibly Damaging	5.27	Benign	0.05	Affected			0	2	1.9	26.03
c.1631G>A	R544Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R544Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438874‑G‑A). Prediction tools that classify the change as benign include FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are REVEL, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta and Rosetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is not contradictory to the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038858	Structured	0.016004	Uncertain	0.967	0.333	0.000	Uncertain		1	6-33438874-G-A	1	6.20e-7	-10.281	Likely Pathogenic	0.596	Likely Pathogenic	Likely Benign	0.542	Likely Pathogenic	0.2103	0.1959		0.19	Likely Benign	0.2	0.87	Ambiguous	0.53	Ambiguous	1.40	Destabilizing	-2.41	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.09	Tolerated	3.37	35	1	1	1.0	-28.06
c.3974C>A	P1325H 2D AIThe SynGAP1 missense variant P1325H is reported in gnomAD (variant ID 6‑33451848‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No result is available from the Foldetta stability analysis. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.893621	Binding	0.439	0.791	0.875				6-33451848-C-A			-6.970	Likely Benign	0.136	Likely Benign	Likely Benign	0.056	Likely Benign	0.2103	0.4364											0.10	Neutral	0.704	Possibly Damaging	0.187	Benign	4.04	Benign	0.00	Affected	4.32	1	-2	0	-1.6	40.02
c.215G>T	R72L 2D AIThe SynGAP1 missense variant R72L is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Pathogenicity is suggested only by polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for R72L, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.455349	Uncertain	0.355	0.819	0.375							-3.102	Likely Benign	0.476	Ambiguous	Likely Benign	0.108	Likely Benign	0.2104	0.4352											-1.49	Neutral	0.686	Possibly Damaging	0.250	Benign	4.12	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.1271T>C	V424A 2D 3DClick to see structure in 3D Viewer AISynGAP1 V424A is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on benign impact are REVEL and FATHMM, whereas the remaining tools—SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as unavailable, SGM‑Consensus as likely pathogenic, and Foldetta as pathogenic. Based on the collective evidence, the variant is most likely pathogenic; this conclusion is not contradicted by the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000							-9.665	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.245	Likely Benign	0.2105	0.1355		2.31	Destabilizing	0.1	2.54	Destabilizing	2.43	Destabilizing	2.10	Destabilizing	-3.45	Deleterious	0.997	Probably Damaging	0.961	Probably Damaging	3.39	Benign	0.01	Affected			0	0	-2.4	-28.05