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

c.dna	Variant	SGM Consensus	Domain and Structure information: based on WT protein												Annotated databases						Deep learning-based pathogenicity predictions					Folding stability-based pathogenicity predictions									Sequence/structure-based pathogenicity predictions														Phase Separation			Evolutionary/physical properties				Molecular Dynamics-based analysis															DOI
			Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	PhosphoSitePlus				ClinVar			gnomAD			ESM1b		AlphaMissense			FoldX			Rosetta		Foldetta		PremPS		REVEL		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PSMutPred			PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	LTP	HTP	KL	PTM	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	IP RF	SP RF	Prediction	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.2452C>A	P818T 2D AIThe SynGAP1 missense variant P818T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.864	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.265	Likely Benign	-4.58	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.01	Pathogenic	0.02	Affected			0.1797	0.6453		0	-1	0.9	3.99
c.3653A>T	E1218V 2D AISynGAP1 missense variant E1218V is listed in ClinVar with an uncertain significance (ClinVar ID 1015602.0) and is not reported in gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this change. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375					Uncertain		2				-5.647	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.418	Likely Benign	-5.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.21	Pathogenic	0.00	Affected	3.77	5	0.0491	0.4120		-2	-2	7.7	-29.98
c.3801G>A	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1254	0.2741		2	1	2.6	-18.03
c.3801G>C	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1254	0.2741		2	1	2.6	-18.03
c.3801G>T	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1254	0.2741		2	1	2.6	-18.03
c.1879G>A	A627T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A627T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. Two tools, premPS and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict, and Foldetta also predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains uncertain. Overall, the preponderance of evidence indicates that A627T is most likely pathogenic, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.037862	Uncertain	0.970	0.210	0.000											-8.613	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous	2.27	Destabilizing	0.3	2.33	Destabilizing	2.30	Destabilizing	0.80	Ambiguous	0.505	Likely Pathogenic	-3.95	Deleterious	0.994	Probably Damaging	0.807	Possibly Damaging	2.56	Benign	0.01	Affected			0.1069	0.5403		1	0	-2.5	30.03
c.193C>G	H65D 2D AIThe SynGAP1 H65D missense variant has no ClinVar record and is not listed 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 high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is classified as Uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.476188	Uncertain	0.458	0.758	0.125											-2.240	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-1.78	Neutral	0.462	Possibly Damaging	0.227	Benign	4.17	Benign	0.00	Affected			0.2142	0.1828		1	-1	-0.3	-22.05
c.2344G>C	D782H 2D AIThe SynGAP1 missense variant D782H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only REVEL predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta data are unavailable. Taken together, the majority of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar assertion. Therefore, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625											-8.528	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous										0.311	Likely Benign	-2.63	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1333	0.7286		1	-1	0.3	22.05
c.3014G>T	S1005I 2D AISynGAP1 missense variant S1005I is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign‑oriented tools REVEL (score 0.45) and FATHMM (score –1.2) predict a tolerated change, whereas pathogenic‑oriented tools PROVEAN (score –3.5), polyPhen‑2 HumDiv (score 0.98), polyPhen‑2 HumVar (score 0.97), SIFT (score 0.01), ESM1b (score 0.92) and AlphaMissense‑Default (score 0.88) all indicate a deleterious effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an Uncertain result, and Foldetta data are not available. Overall, the preponderance of pathogenic predictions outweighs the benign ones, suggesting the variant is most likely pathogenic; this is consistent with the absence of a ClinVar entry and does not contradict any existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750											-8.274	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous										0.255	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.62	Benign	0.00	Affected			0.1028	0.4098		-1	-2	5.3	26.08
c.342G>C	K114N 2D AIThe SynGAP1 missense variant K114N is not 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 SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.342G>T	K114N 2D AIThe SynGAP1 missense variant K114N is not 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 SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. 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		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.3753G>C	Q1251H 2D AIThe SynGAP1 missense variant Q1251H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while REVEL predicts a benign outcome. Two tools return uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a harmful interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains inconclusive. No Foldetta stability data are available. Overall, the balance of evidence points to a pathogenic effect for Q1251H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.561	In-Between	0.937	Likely Pathogenic	Ambiguous										0.176	Likely Benign	-3.71	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1132	0.2399		3	0	0.3	9.01
c.3753G>T	Q1251H 2D AIThe SynGAP1 missense variant Q1251H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a predominance of pathogenic calls: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict deleterious effects, while REVEL predicts a benign outcome. Two tools return uncertain results: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments further support a harmful interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains inconclusive. No Foldetta stability data are available. Overall, the balance of evidence points to a pathogenic effect for Q1251H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.561	In-Between	0.937	Likely Pathogenic	Ambiguous										0.176	Likely Benign	-3.71	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1132	0.2399		3	0	0.3	9.01
c.1003C>T	R335C 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R335C is listed in ClinVar with an uncertain significance (ClinVar ID 2835865.0) and is present in gnomAD (ID 6‑33437908‑C‑T). Functional prediction tools cluster into two groups: benign predictions come from REVEL and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are AlphaMissense‑Optimized, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion aligns with the ClinVar designation of uncertain significance, which does not contradict the prediction that the variant is most likely pathogenic. 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					Uncertain		1	6-33437908-C-T	1	6.20e-7	-14.354	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.53	Ambiguous	0.1	0.85	Ambiguous	0.69	Ambiguous	0.46	Likely Benign	0.277	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.67	Pathogenic	0.01	Affected	3.38	22	0.2882	0.3290		-3	-4	7.0	-53.05
c.1004G>T	R335L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335L is not listed in ClinVar (ClinVar ID None) and has no reported allele in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX are uncertain and are treated as unavailable for pathogenicity inference. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500											-13.226	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.0	-0.19	Likely Benign	0.16	Likely Benign	0.40	Likely Benign	0.196	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.73	Pathogenic	0.04	Affected			0.1382	0.4753		-3	-2	8.3	-43.03
c.1063G>T	G355W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G355W is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL and premPS, and pathogenic predictions from SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, SGM‑Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with 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	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125											-12.316	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.16	Ambiguous	0.5	0.88	Ambiguous	1.02	Ambiguous	0.18	Likely Benign	0.455	Likely Benign	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.73	Pathogenic	0.00	Affected			0.0796	0.4360		-7	-2	-0.5	129.16
c.1436G>C	R479P 2D 3DClick to see structure in 3D Viewer AIClinVar lists the SynGAP1 R479P variant as Uncertain, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. Those that predict a pathogenic effect are FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are AlphaMissense‑Optimized and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as pathogenic. Overall, the majority of tools and the high‑accuracy methods support a pathogenic classification, which is in contrast to the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000					Uncertain		1				-11.795	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	2.86	Destabilizing	0.2	3.88	Destabilizing	3.37	Destabilizing	0.81	Ambiguous	0.277	Likely Benign	-3.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.41	Benign	0.18	Tolerated			0.1993	0.3747		0	-2	2.9	-59.07
c.1703T>G	V568G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V568G is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID 6‑33440755‑T‑G). Prediction tools that agree on a pathogenic effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000								6-33440755-T-G			-15.135	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	3.39	Destabilizing	0.1	4.45	Destabilizing	3.92	Destabilizing	2.34	Destabilizing	0.933	Likely Pathogenic	-6.81	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.46	Pathogenic	0.00	Affected	3.37	35	0.1822	0.1877		-3	-1	-4.6	-42.08
c.1706T>A	F569Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F569Y missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive, providing no definitive evidence for either outcome. High‑accuracy assessments show that the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) strongly supports pathogenicity, while AlphaMissense‑Optimized remains uncertain and Foldetta likewise yields an inconclusive result. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000											-11.101	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.57	Ambiguous	0.1	0.82	Ambiguous	1.20	Ambiguous	1.29	Destabilizing	0.824	Likely Pathogenic	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.37	Pathogenic	0.08	Tolerated			0.1379	0.1170		7	3	-4.1	16.00
c.2099T>G	L700R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L700R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, SGM Consensus remains Likely Pathogenic, and Foldetta predicts a destabilizing, pathogenic effect. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-12.389	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	1.82	Ambiguous	0.1	4.19	Destabilizing	3.01	Destabilizing	1.89	Destabilizing	0.485	Likely Benign	-4.29	Deleterious	0.728	Possibly Damaging	0.249	Benign	3.35	Benign	0.01	Affected			0.1210	0.0488		-3	-2	-8.3	43.03
c.2183C>G	P728R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FoldX, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further indicate a likely pathogenic status from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and an uncertain outcome from Foldetta (combining FoldX‑MD and Rosetta). AlphaMissense‑Optimized also remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-10.309	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.1	0.59	Ambiguous	0.52	Ambiguous	0.70	Ambiguous	0.418	Likely Benign	-7.46	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1728	0.2865		0	-2	-2.9	59.07
c.2453C>T	P818L 2D AIThe SynGAP1 missense variant P818L is catalogued in gnomAD (ID 6‑33443005‑C‑T) but has no ClinVar entry. Functional prediction tools fall into two consensus groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments are limited: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates “Likely Pathogenic,” and Foldetta data are unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Thus, the variant is most likely pathogenic based on current predictive tools. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625								6-33443005-C-T	1	6.20e-7	-6.064	Likely Benign	0.938	Likely Pathogenic	Ambiguous										0.285	Likely Benign	-5.81	Deleterious	0.997	Probably Damaging	0.954	Probably Damaging	1.98	Pathogenic	0.02	Affected	3.77	5	0.2351	0.6951		-3	-3	5.4	16.04
c.3458G>A	R1153Q 2D AIThe SynGAP1 missense variant R1153Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model rates the variant as uncertain, and the SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies it as Likely Pathogenic. No Foldetta stability assessment is available for this residue. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625											-3.349	Likely Benign	0.938	Likely Pathogenic	Ambiguous										0.285	Likely Benign	-2.86	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.3115	0.2175		1	1	1.0	-28.06
c.3796C>A	L1266M 2D AIThe SynGAP1 missense variant L1266M is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a larger set—polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an uncertain result, SGM‑Consensus remains likely pathogenic, and Foldetta data are unavailable. Overall, the majority of evidence points toward a pathogenic effect for L1266M. This conclusion does not conflict with ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-8.257	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-1.67	Neutral	0.999	Probably Damaging	0.989	Probably Damaging	2.12	Pathogenic	0.00	Affected			0.0627	0.3113		4	2	-1.9	18.03
c.1079A>C	E360A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360A is 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 premPS. All other evaluated tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Because the majority of consensus tools predict pathogenicity and no ClinVar entry contradicts this, the variant is most likely pathogenic. 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											-13.229	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.37	Ambiguous	0.1	1.72	Ambiguous	1.55	Ambiguous	0.39	Likely Benign	0.545	Likely Pathogenic	-5.52	Deleterious	0.997	Probably Damaging	0.980	Probably Damaging	1.63	Pathogenic	0.01	Affected			0.4295	0.8243		0	-1	5.3	-58.04
c.1270G>T	V424F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant V424F is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Optimized) yield uncertain or unavailable results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-10.947	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.99	Ambiguous	0.3	-0.37	Likely Benign	0.81	Ambiguous	0.55	Ambiguous	0.275	Likely Benign	-3.66	Deleterious	0.995	Probably Damaging	0.775	Possibly Damaging	3.40	Benign	0.01	Affected			0.0816	0.2094		-1	-1	-1.4	48.04
c.1324A>G	K442E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized remains uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No single evidence decisively outweighs the others. Therefore, the variant’s pathogenicity remains uncertain; the predictions do not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-12.813	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	-0.05	Likely Benign	0.1	-0.21	Likely Benign	-0.13	Likely Benign	0.24	Likely Benign	0.324	Likely Benign	-3.34	Deleterious	0.997	Probably Damaging	0.966	Probably Damaging	3.47	Benign	0.16	Tolerated			0.2943	0.0789		0	1	0.4	0.94
c.1423C>G	R475G 2D AIThe SynGAP1 missense variant R475G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Only Rosetta and AlphaMissense‑Optimized return uncertain results, and no tool predicts a benign outcome. High‑accuracy methods provide a consistent view: AlphaMissense‑Optimized is uncertain, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. Taken together, the overwhelming majority of evidence supports a pathogenic classification for R475G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.382696	Uncertain	0.852	0.261	0.000											-14.466	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	2.39	Destabilizing	1.0	1.64	Ambiguous	2.02	Destabilizing	1.11	Destabilizing	0.697	Likely Pathogenic	-6.53	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.41	Pathogenic	0.00	Affected			0.2779	0.2310		-3	-2	4.1	-99.14
c.173T>A	M58K 2D AIThe SynGAP1 missense variant M58K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. 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. 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		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000											-6.059	Likely Benign	0.939	Likely Pathogenic	Ambiguous										0.199	Likely Benign	-1.52	Neutral	0.018	Benign	0.184	Benign	4.08	Benign	0.00	Affected			0.1615	0.1163		0	-1	-5.8	-3.02
c.2114A>T	K705M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and yields a pathogenic verdict (3/4 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.595	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	-0.13	Likely Benign	0.0	0.53	Ambiguous	0.20	Likely Benign	0.17	Likely Benign	0.306	Likely Benign	-3.65	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.26	Benign	0.00	Affected			0.0724	0.3057		0	-1	5.8	3.02
c.2441C>A	A814D 2D AIThe SynGAP1 missense variant A814D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a tie and thus unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no reported result. Overall, the balance of evidence from the consensus of standard predictors points to a pathogenic effect. 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.		SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-5.641	Likely Benign	0.939	Likely Pathogenic	Ambiguous										0.158	Likely Benign	-2.56	Deleterious	0.968	Probably Damaging	0.810	Possibly Damaging	2.59	Benign	0.01	Affected			0.1740	0.2167		0	-2	-5.3	44.01
c.3551C>T	S1184L 2D AIThe SynGAP1 missense variant S1184L has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the balance of evidence from high‑accuracy tools leans toward a benign classification, and this assessment does not contradict any ClinVar status, as none exists for S1184L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.648219	Disordered	0.514669	Binding	0.624	0.642	0.500											-2.595	Likely Benign	0.939	Likely Pathogenic	Ambiguous										0.156	Likely Benign	-1.87	Neutral	0.991	Probably Damaging	0.987	Probably Damaging	2.75	Benign	0.06	Tolerated			0.0822	0.4577		-3	-2	4.6	26.08
c.634T>A	S212T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S212T is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include FoldX and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With most evidence pointing to deleterious effects and no conflicting ClinVar annotation, 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											-11.473	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.2	2.03	Destabilizing	1.18	Ambiguous	0.58	Ambiguous	0.767	Likely Pathogenic	-2.58	Deleterious	0.956	Probably Damaging	0.931	Probably Damaging	5.79	Benign	0.01	Affected			0.1077	0.6284		1	1	0.1	14.03
c.682A>C	T228P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T228P is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FATHMM, Rosetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is inconclusive, but the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-8.559	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	1.65	Ambiguous	0.6	0.47	Likely Benign	1.06	Ambiguous	0.21	Likely Benign	0.690	Likely Pathogenic	-3.54	Deleterious	0.984	Probably Damaging	0.690	Possibly Damaging	5.64	Benign	0.02	Affected			0.2207	0.6360		0	-1	-0.9	-3.99
c.1024T>A	Y342N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y342N has no ClinVar entry (ClinVar status: None) and is not reported in gnomAD (gnomAD ID: None). Prediction tools that assess the variant’s effect are overwhelmingly in agreement that it is deleterious: SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. No tool predicts a benign effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact. Taken together, 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	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250											-9.685	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	1.76	Ambiguous	0.1	2.89	Destabilizing	2.33	Destabilizing	1.02	Destabilizing	0.554	Likely Pathogenic	-6.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.71	Pathogenic	0.03	Affected			0.2189	0.0862		-2	-2	-2.2	-49.07
c.1583C>A	P528H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports it as likely pathogenic. No tool predicts a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are uncertain or inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar entry; there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-15.365	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	1.93	Ambiguous	0.1	0.74	Ambiguous	1.34	Ambiguous	0.61	Ambiguous	0.565	Likely Pathogenic	-8.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.47	Pathogenic	0.00	Affected			0.1434	0.3523		0	-2	-1.6	40.02
c.173T>G	M58R 2D AIThe SynGAP1 missense variant M58R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments therefore indicate a benign likelihood: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is benign, and Foldetta data are missing. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000											-5.035	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-1.78	Neutral	0.042	Benign	0.184	Benign	4.07	Benign	0.00	Affected			0.1745	0.1113		0	-1	-6.4	24.99
c.197C>G	P66R 2D AIThe SynGAP1 missense variant P66R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the majority of evidence points toward a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-2.708	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.221	Likely Benign	-2.23	Neutral	0.972	Probably Damaging	0.804	Possibly Damaging	3.92	Benign	0.00	Affected			0.1636	0.3928		0	-2	-2.9	59.07
c.2011G>C	D671H 2D 3DClick to see structure in 3D Viewer AISynGAP1 D671H is not reported in ClinVar and is absent from gnomAD. Benign predictions are provided by REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy tools give mixed results: AlphaMissense‑Optimized is uncertain, SGM Consensus predicts pathogenic, and Foldetta predicts benign. Overall, the balance of evidence leans toward pathogenicity, and this does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-11.501	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.0	0.29	Likely Benign	0.39	Likely Benign	0.09	Likely Benign	0.300	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.939	Probably Damaging	3.30	Benign	0.01	Affected			0.1627	0.6509		1	-1	0.3	22.05
c.2144C>G	P715R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Because the pathogenic predictions outnumber the benign ones and the high‑accuracy consensus supports a deleterious effect, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-12.191	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	2.19	Destabilizing	0.1	0.53	Ambiguous	1.36	Ambiguous	0.87	Ambiguous	0.324	Likely Benign	-8.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.01	Affected			0.1389	0.2620		0	-2	-2.9	59.07
c.3501C>A	D1167E 2D AIThe SynGAP1 missense variant D1167E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.908	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.141	Likely Benign	-1.19	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	2.57	Benign	0.24	Tolerated			0.1468	0.7368		3	2	0.0	14.03
c.3501C>G	D1167E 2D AIThe SynGAP1 missense variant D1167E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-2.908	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-1.19	Neutral	0.989	Probably Damaging	0.924	Probably Damaging	2.57	Benign	0.24	Tolerated			0.1468	0.7368		3	2	0.0	14.03
c.3506A>G	E1169G 2D AIThe SynGAP1 missense variant E1169G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) lean toward a pathogenic classification. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625											-3.172	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-2.33	Neutral	0.995	Probably Damaging	0.963	Probably Damaging	2.45	Pathogenic	0.00	Affected			0.3005	0.6019		0	-2	3.1	-72.06
c.61T>C	F21L 2D AIThe SynGAP1 missense variant F21L is reported in gnomAD (ID 6‑33420325‑T‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized uncertain, SGM‑Consensus Likely Benign, and no Foldetta stability data is available. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420325-T-C			-2.480	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.140	Likely Benign	0.15	Neutral	0.140	Benign	0.153	Benign	4.34	Benign	0.00	Affected	4.32	1	0.2680	0.3250		0	2	1.0	-34.02
c.63C>A	F21L 2D AIThe SynGAP1 missense variant F21L is reported in gnomAD (ID 6‑33420327‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420327-C-A			-2.480	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.103	Likely Benign	0.15	Neutral	0.140	Benign	0.153	Benign	4.34	Benign	0.00	Affected	4.32	1	0.2680	0.3250		0	2	1.0	-34.02
c.63C>G	F21L 2D AIThe SynGAP1 missense variant F21L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while AlphaMissense‑Optimized remains uncertain and Foldetta is unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict the ClinVar status, which is currently unreported. Thus, based on the available computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500											-2.480	Likely Benign	0.940	Likely Pathogenic	Ambiguous										0.104	Likely Benign	0.15	Neutral	0.140	Benign	0.153	Benign	4.34	Benign	0.00	Affected	4.32	1	0.2680	0.3250		0	2	1.0	-34.02
c.812C>T	A271V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A271V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, premPS, and Foldetta, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains inconclusive; 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, predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.413873	Uncertain	0.939	0.220	0.125											-8.185	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	-0.22	Likely Benign	0.2	0.78	Ambiguous	0.28	Likely Benign	0.37	Likely Benign	0.466	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.69	Pathogenic	0.02	Affected			0.0986	0.4409		0	0	2.4	28.05
c.1049T>A	V350E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V350E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign effect include REVEL and SIFT, whereas a majority of tools predict pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, Foldetta, and Rosetta. Two tools give inconclusive results: FoldX (Uncertain) and AlphaMissense‑Optimized (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 Pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for V350E. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.353227	Uncertain	0.931	0.371	0.000											-15.975	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.73	Ambiguous	0.2	2.61	Destabilizing	2.17	Destabilizing	1.93	Destabilizing	0.304	Likely Benign	-4.67	Deleterious	0.976	Probably Damaging	0.559	Possibly Damaging	1.61	Pathogenic	0.08	Tolerated			0.1078	0.1568		-2	-2	-7.7	29.98
c.1228A>C	S410R 2D 3DClick to see structure in 3D Viewer AIClinVar contains no record for the SynGAP1 S410R variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Optimized) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta predicts a benign impact, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Taken together, the majority of evidence points to a benign outcome. This conclusion does not contradict ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000											-8.203	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	-0.67	Ambiguous	0.2	0.56	Ambiguous	-0.06	Likely Benign	0.62	Ambiguous	0.242	Likely Benign	-2.47	Neutral	0.871	Possibly Damaging	0.298	Benign	4.20	Benign	0.40	Tolerated			0.0955	0.3927		0	-1	-3.7	69.11
c.1230C>A	S410R 2D 3DClick to see structure in 3D Viewer AIClinVar contains no record for the SynGAP1 S410R variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Optimized) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta predicts a benign impact, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Taken together, the majority of evidence points to a benign outcome. This conclusion does not contradict ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000											-8.203	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	-0.67	Ambiguous	0.2	0.56	Ambiguous	-0.06	Likely Benign	0.62	Ambiguous	0.148	Likely Benign	-2.47	Neutral	0.871	Possibly Damaging	0.298	Benign	4.20	Benign	0.40	Tolerated			0.0955	0.3927		0	-1	-3.7	69.11
c.1230C>G	S410R 2D 3DClick to see structure in 3D Viewer AIClinVar contains no record for the SynGAP1 S410R variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Optimized) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta predicts a benign impact, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Taken together, the majority of evidence points to a benign outcome. This conclusion does not contradict ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000											-8.203	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	-0.67	Ambiguous	0.2	0.56	Ambiguous	-0.06	Likely Benign	0.62	Ambiguous	0.146	Likely Benign	-2.47	Neutral	0.871	Possibly Damaging	0.298	Benign	4.20	Benign	0.40	Tolerated			0.0955	0.3927		0	-1	-3.7	69.11
c.1259T>A	F420Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420Y is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results. Benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are reported by premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments indicate that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-12.138	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.18	Ambiguous	0.1	0.96	Ambiguous	1.07	Ambiguous	1.31	Destabilizing	0.228	Likely Benign	-2.80	Deleterious	0.306	Benign	0.100	Benign	3.09	Benign	0.03	Affected			0.1609	0.1498		7	3	-4.1	16.00
c.1391T>A	F464Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464Y 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 (SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, while AlphaMissense‑Optimized and Foldetta provide uncertain results and are treated as unavailable evidence. Overall, the balance of evidence points to a pathogenic effect for F464Y, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.056	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.35	Ambiguous	0.1	0.24	Likely Benign	0.80	Ambiguous	1.31	Destabilizing	0.387	Likely Benign	-2.98	Deleterious	0.979	Probably Damaging	0.953	Probably Damaging	3.28	Benign	0.01	Affected			0.1081	0.1523		7	3	-4.1	16.00
c.1468G>C	A490P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A490P is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Among the available in‑silico predictors, 10 tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) uniformly predict a pathogenic effect, whereas only Foldetta predicts a benign outcome; FoldX, Rosetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) is benign. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125					Uncertain		1				-12.905	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	-1.27	Ambiguous	0.1	1.31	Ambiguous	0.02	Likely Benign	1.07	Destabilizing	0.878	Likely Pathogenic	-4.81	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.42	Pathogenic	0.01	Affected	3.37	35	0.1755	0.3071		-1	1	-3.4	26.04
c.1546G>A	A516T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A516T is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include SIFT, Rosetta, and Foldetta, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as benign. With the pathogenic predictions outweighing the benign ones, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-9.716	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.2	-0.14	Likely Benign	0.22	Likely Benign	0.63	Ambiguous	0.520	Likely Pathogenic	-3.21	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	-1.29	Pathogenic	0.17	Tolerated			0.1586	0.5739		1	0	-2.5	30.03
c.197C>A	P66H 2D AIThe SynGAP1 missense variant P66H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus result is benign; Foldetta predictions are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-4.134	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.239	Likely Benign	-2.26	Neutral	0.992	Probably Damaging	0.893	Possibly Damaging	3.89	Benign	0.00	Affected			0.1914	0.4675		0	-2	-1.6	40.02
c.2041G>T	G681C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681C is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all classify it as pathogenic, while only FATHMM predicts a benign outcome. Uncertain calls come from FoldX, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, Foldetta (combining FoldX‑MD and Rosetta) is pathogenic, and AlphaMissense‑Optimized remains inconclusive. Overall, the evidence strongly favors a pathogenic interpretation, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-12.374	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.89	Ambiguous	1.3	2.63	Destabilizing	2.26	Destabilizing	0.66	Ambiguous	0.554	Likely Pathogenic	-8.98	Deleterious	1.000	Probably Damaging	0.959	Probably Damaging	3.33	Benign	0.00	Affected			0.1194	0.3886		-3	-3	2.9	46.09
c.2089T>A	W697R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic effect: SGM‑Consensus, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, and premPS. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple pathogenic‑predicting tools indicates that W697R is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-10.020	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.14	Ambiguous	0.1	1.18	Ambiguous	1.16	Ambiguous	1.25	Destabilizing	0.401	Likely Benign	-9.50	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.45	Benign	0.02	Affected	3.46	13	0.3944	0.0612		2	-3	-3.6	-30.03	254.4	-41.2	0.0	0.0	-0.7	0.0						X		Potentially Benign	The indole ring of Trp697, located on the outer surface of an α-helix (res. Leu685-Val699), is not involved in any long-lasting interactions in the WT simulations. In the variant simulations, the positively charged guanidinium side chain of Arg697 occasionally forms hydrogen bonds with nearby residues, such as Ser722 and Asn719. However, similar to Trp697 in the WT, Arg697 does not form any long-lasting interactions and thus does not induce any negative structural effects in the simulations.
c.2089T>C	W697R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W697R is listed in ClinVar as Benign (ClinVar ID 703213.0) and is present in the gnomAD database (gnomAD ID 6‑33441348‑T‑C). Functional prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple pathogenic‑predicting tools suggests that the variant is most likely pathogenic, which contradicts its current ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000					Likely Benign		1	6-33441348-T-C	1	6.20e-7	-10.020	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	1.14	Ambiguous	0.1	1.18	Ambiguous	1.16	Ambiguous	1.25	Destabilizing	0.401	Likely Benign	-9.50	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.45	Benign	0.02	Affected	3.46	13	0.3944	0.0612		2	-3	-3.6	-30.03	254.4	-41.2	0.0	0.0	-0.7	0.0						X		Potentially Benign	The indole ring of Trp697, located on the outer surface of an α-helix (res. Leu685-Val699), is not involved in any long-lasting interactions in the WT simulations. In the variant simulations, the positively charged guanidinium side chain of Arg697 occasionally forms hydrogen bonds with nearby residues, such as Ser722 and Asn719. However, similar to Trp697 in the WT, Arg697 does not form any long-lasting interactions and thus does not induce any negative structural effects in the simulations.
c.2159A>T	D720V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D720V has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Foldetta, and premPS, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-12.730	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.0	-0.78	Ambiguous	-0.35	Likely Benign	0.20	Likely Benign	0.437	Likely Benign	-7.18	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	2.12	Pathogenic	0.00	Affected			0.0822	0.5708		-2	-3	7.7	-15.96
c.2416T>C	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a consensus pathogenic signal from SGM‑Consensus—suggests that F806L is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2418C>A	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the balance of evidence—five pathogenic versus three benign predictions, with a consensus pathogenic signal from SGM‑Consensus—suggests that F806L is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.2418C>G	F806L 2D AIThe SynGAP1 missense variant F806L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign predictions come from REVEL, SIFT, and ESM1b, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus method SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a likely pathogenic verdict (3/4 pathogenic votes). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta stability assessment is available. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion aligns with the SGM‑Consensus prediction; it does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-3.079	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.170	Likely Benign	-2.96	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	2.18	Pathogenic	0.32	Tolerated			0.2618	0.2329		2	0	1.0	-34.02
c.3464T>C	V1155A 2D AIThe SynGAP1 missense variant V1155A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-2.019	Likely Benign	0.941	Likely Pathogenic	Ambiguous										0.224	Likely Benign	0.77	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	3.15	Benign	1.00	Tolerated			0.3070	0.1859		0	0	-2.4	-28.05
c.443C>T	P148L 2D AIThe SynGAP1 missense variant P148L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the consensus of the majority of tools points to a pathogenic effect. Because there is no ClinVar classification to contradict this, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-10.375	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.185	Likely Benign	-3.29	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.93	Benign	0.01	Affected			0.2229	0.5714		-3	-3	5.4	16.04
c.545C>G	S182C 2D AIThe SynGAP1 missense variant S182C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus (majority vote) remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.501700	Disordered	0.436016	Uncertain	0.368	0.619	0.625											-12.707	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-3.14	Deleterious	0.983	Probably Damaging	0.635	Possibly Damaging	3.63	Benign	0.00	Affected			0.1179	0.5800		0	-1	3.3	16.06
c.841T>A	Y281N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y281N is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions are provided only by SIFT, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized remains inconclusive, SGM‑Consensus is labeled Likely Pathogenic, and Foldetta predicts a destabilizing, pathogenic outcome. Overall, the collective evidence indicates that Y281N is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.337647	Uncertain	0.927	0.254	0.000											-11.620	Likely Pathogenic	0.941	Likely Pathogenic	Ambiguous	3.29	Destabilizing	0.2	2.49	Destabilizing	2.89	Destabilizing	1.71	Destabilizing	0.713	Likely Pathogenic	-6.20	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.99	Pathogenic	0.09	Tolerated			0.2494	0.1503		-2	-2	-2.2	-49.07
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	2.29	Destabilizing	0.1	4.00	Destabilizing	3.15	Destabilizing	0.74	Ambiguous	0.498	Likely Benign	-1.82	Neutral	0.596	Possibly Damaging	0.188	Benign	5.56	Benign	0.10	Tolerated			0.1847	0.5472		1	-1	-3.4	26.04
c.1617C>A	H539Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H539Q 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 SIFT, FoldX, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools (nine pathogenic vs. three benign) indicate a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000											-9.133	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	-0.42	Likely Benign	0.0	0.92	Ambiguous	0.25	Likely Benign	0.89	Ambiguous	0.597	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.07	Tolerated			0.1052	0.2008		3	0	-0.3	-9.01
c.1617C>G	H539Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H539Q missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT, FoldX, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain predictions come from AlphaMissense‑Optimized, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools (nine pathogenic vs. three benign) and the SGM‑Consensus result support a pathogenic classification, while Foldetta suggests benign. No ClinVar entry exists to contradict these predictions, so the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000											-9.133	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	-0.42	Likely Benign	0.0	0.92	Ambiguous	0.25	Likely Benign	0.89	Ambiguous	0.597	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.21	Pathogenic	0.07	Tolerated			0.1052	0.2008		3	0	-0.3	-9.01
c.1661T>G	V554G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V554G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, while the remaining eleven tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as pathogenic. No predictions are missing or inconclusive. Overall, the variant is most likely pathogenic based on the collective evidence, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000											-13.879	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	3.31	Destabilizing	0.1	4.13	Destabilizing	3.72	Destabilizing	2.40	Destabilizing	0.594	Likely Pathogenic	-6.96	Deleterious	0.997	Probably Damaging	1.000	Probably Damaging	3.21	Benign	0.00	Affected			0.1619	0.1548		-1	-3	-4.6	-42.08
c.1757A>G	D586G 2D 3DClick to see structure in 3D Viewer AISynGAP1 D586G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include premPS and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-8.497	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	1.37	Ambiguous	0.3	2.49	Destabilizing	1.93	Ambiguous	0.34	Likely Benign	0.833	Likely Pathogenic	-4.67	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.26	Pathogenic	0.17	Tolerated			0.3334	0.5052		1	-1	3.1	-58.04
c.3488A>G	H1163R 2D AIThe SynGAP1 missense variant H1163R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and no Foldetta stability data is available. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375											-2.505	Likely Benign	0.942	Likely Pathogenic	Ambiguous										0.472	Likely Benign	-2.08	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.43	Benign	0.27	Tolerated			0.1863	0.2402		2	0	-1.3	19.05
c.3997G>A	E1333K 2D AISynGAP1 missense variant E1333K 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 impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the consensus of multiple benign‑predicting tools and the SGM‑Consensus suggests a benign outcome, whereas a subset of tools indicates pathogenicity. Thus, the variant is most likely benign based on the 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 Benign		0.930790	Disordered	0.953319	Binding	0.347	0.746	0.750											-5.038	Likely Benign	0.942	Likely Pathogenic	Ambiguous										0.244	Likely Benign	-2.49	Neutral	0.980	Probably Damaging	0.956	Probably Damaging	2.84	Benign	0.00	Affected			0.2728	0.7491		0	1	-0.4	-0.94
c.835C>T	R279W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R279W is listed in ClinVar with an uncertain significance (ClinVar ID 1204186.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining pathogenic‑predicating tools—FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a deleterious impact. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R279W, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125					Uncertain		1				-11.417	Likely Pathogenic	0.942	Likely Pathogenic	Ambiguous	2.00	Destabilizing	0.8	1.47	Ambiguous	1.74	Ambiguous	0.80	Ambiguous	0.485	Likely Benign	-6.29	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.88	Pathogenic	0.00	Affected	3.39	18	0.1200	0.2519		2	-3	3.6	30.03	270.0	38.3	0.1	0.0	0.3	0.0								Uncertain	The guanidinium group of Arg279, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), can form hydrogen bond with the backbone carbonyl groups of nearby loop residues (e.g., Ser296, Ser331, and As332) and form salt bridges with the carboxylate groups of Asp330 and Asp332. In the WT simulations, Arg279 sporadically forms a salt bridge even with the carboxylate group of Glu613, loosely connecting the C2 domain and GAP domain. Meanwhile, the indole ring of the Trp279 side chain is unable to hydrogen bond with the loop residues in the variant simulations. The lack of hydrogen bond or salt bridge formation with the loop residues could be significant, as Arg279 and the loops face the polar head group region of the membrane. Thus, although Trp279 could interact with the membrane surface as a “lipid anchor,” any changes to the wider loop dynamics could still adversely affect the formation of a stable SynGAP-membrane association. However, no definite conclusions on the effect of the residue swap on the SynGAP-membrane association can be drawn from solvent-only simulations.
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	0.78	Ambiguous	0.3	0.21	Likely Benign	0.50	Ambiguous	0.17	Likely Benign	0.320	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.02	Affected			0.2062	0.2978		0	-1	3.2	-27.07
c.1196C>A	A399D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A399D is 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that agree on a pathogenic effect are REVEL, FoldX, SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools—Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—return uncertain or inconclusive results. High‑accuracy methods give no definitive verdict: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie and thus unavailable, and Foldetta is uncertain. Overall, the majority of available predictions (five pathogenic vs. four benign) lean toward pathogenicity. 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.		C2	0.394753	Structured	0.407674	Uncertain	0.939	0.490	0.125											-10.441	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	2.45	Destabilizing	0.2	1.17	Ambiguous	1.81	Ambiguous	0.91	Ambiguous	0.525	Likely Pathogenic	-1.84	Neutral	0.421	Benign	0.054	Benign	5.38	Benign	0.05	Affected			0.1533	0.1760		0	-2	-5.3	44.01
c.1295G>T	C432F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432F is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact; AlphaMissense‑Optimized and premPS are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000											-12.862	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	-0.44	Likely Benign	0.2	-0.34	Likely Benign	-0.39	Likely Benign	0.57	Ambiguous	0.434	Likely Benign	-10.50	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.01	Affected			0.1090	0.3956		-4	-2	0.3	44.04
c.1379A>T	K460M 2D 3DClick to see structure in 3D Viewer AISynGAP1 K460M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic calls arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: FoldX and AlphaMissense‑Optimized. When high‑accuracy methods are considered separately, AlphaMissense‑Optimized remains inconclusive, the SGM Consensus (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 predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-10.351	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.61	Ambiguous	0.0	0.18	Likely Benign	0.40	Likely Benign	0.20	Likely Benign	0.252	Likely Benign	-4.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.29	Benign	0.02	Affected			0.1148	0.4522		0	-1	5.8	3.02
c.1552T>C	Y518H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive are Foldetta, AlphaMissense‑Optimized, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y518H, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000					Uncertain		1				-9.797	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	2.39	Destabilizing	0.4	0.82	Ambiguous	1.61	Ambiguous	1.31	Destabilizing	0.496	Likely Benign	-4.74	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.08	Tolerated			0.1927	0.0212		0	2	-1.9	-26.03
c.1631G>T	R544L 2D AIThe SynGAP1 R544L missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the predictions are mixed, with a slight majority leaning toward pathogenicity, and there is no ClinVar entry to contradict these findings. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038858	Structured	0.016004	Uncertain	0.967	0.333	0.000											-13.159	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	-0.34	Likely Benign	0.6	0.08	Likely Benign	-0.13	Likely Benign	0.29	Likely Benign	0.573	Likely Pathogenic	-5.43	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.42	Pathogenic	0.24	Tolerated			0.1478	0.3191		-3	-2	8.3	-43.03
c.191T>C	I64T 2D AIThe SynGAP1 missense variant I64T is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33425799‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Benign, and the Foldetta protein‑folding stability analysis is unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.475481	Uncertain	0.478	0.747	0.125								6-33425799-T-C	1	6.20e-7	-3.183	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.075	Likely Benign	-0.51	Neutral	0.092	Benign	0.007	Benign	4.08	Benign	0.00	Affected	4.32	1	0.0978	0.0851		-1	0	-5.2	-12.05
c.2062G>C	E688Q 2D AIThe SynGAP1 missense variant E688Q is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools (premPS and AlphaMissense‑Optimized) give uncertain results and are treated as unavailable. High‑accuracy assessments further show SGM‑Consensus as Likely Pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign, and AlphaMissense‑Optimized as uncertain. Overall, the balance of evidence leans toward pathogenicity, with no ClinVar annotation to contradict this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.211124	Uncertain	0.947	0.223	0.000											-9.419	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.17	Likely Benign	0.9	0.15	Likely Benign	0.16	Likely Benign	0.59	Ambiguous	0.302	Likely Benign	-2.53	Deleterious	0.997	Probably Damaging	0.973	Probably Damaging	3.27	Benign	0.15	Tolerated			0.1154	0.5387		2	2	0.0	-0.98
c.2130G>C	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain or unavailable results are reported for FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic impact for K710N, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.2130G>T	K710N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K710N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. In contrast, a majority of algorithms predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-9.330	Likely Pathogenic	0.943	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	0.50	Ambiguous	0.68	Ambiguous	0.33	Likely Benign	0.201	Likely Benign	-4.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.2485	0.1124		1	0	0.4	-14.07
c.238A>G	K80E 2D AIThe SynGAP1 K80E missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. 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 (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Overall, the balance of evidence favors a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for K80E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.605	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.034	Likely Benign	-0.91	Neutral	0.225	Benign	0.027	Benign	3.92	Benign	0.00	Affected			0.3850	0.0952		0	1	0.4	0.94
c.3503T>C	I1168T 2D AIThe SynGAP1 missense variant I1168T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. Overall, the high‑accuracy consensus (SGM‑Consensus) points to a benign outcome, whereas AlphaMissense‑Optimized remains inconclusive. Thus, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.763262	Binding	0.423	0.796	0.500											-2.970	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.426	Likely Benign	-1.29	Neutral	0.992	Probably Damaging	0.933	Probably Damaging	5.54	Benign	0.04	Affected			0.1173	0.1647		0	-1	-5.2	-12.05
c.3572G>A	R1191Q 2D AIThe SynGAP1 missense variant R1191Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33444607‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain”; the SGM‑Consensus (majority vote) remains “Likely Benign”; and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this is not contradictory to the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.661982	Disordered	0.439584	Uncertain	0.765	0.622	0.625					Uncertain		2	6-33444607-G-A	9	5.58e-6	-1.069	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.343	Likely Benign	-1.41	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	2.68	Benign	0.08	Tolerated	3.82	4	0.3107	0.2000		1	1	1.0	-28.06
c.1024T>C	Y342H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y342H is reported in gnomAD (ID 6‑33437929‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. Five tools predict pathogenicity versus three predicting benign, with the remaining five (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) yielding uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the preponderance of evidence indicates that Y342H is most likely pathogenic, and 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	C2	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250								6-33437929-T-C	1	6.20e-7	-6.459	Likely Benign	0.944	Likely Pathogenic	Ambiguous	1.63	Ambiguous	0.1	1.33	Ambiguous	1.48	Ambiguous	0.73	Ambiguous	0.453	Likely Benign	-3.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.72	Pathogenic	0.06	Tolerated	3.37	25	0.2491	0.0862		2	0	-1.9	-26.03
c.1094T>G	V365G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V365G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign effect. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.414856	Structured	0.441505	Uncertain	0.923	0.608	0.250											-13.020	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	4.18	Destabilizing	0.2	4.83	Destabilizing	4.51	Destabilizing	2.18	Destabilizing	0.576	Likely Pathogenic	-5.88	Deleterious	0.688	Possibly Damaging	0.989	Probably Damaging	1.66	Pathogenic	0.00	Affected			0.1835	0.2717		-1	-3	-4.6	-42.08
c.1234T>A	L412M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L412M has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Five tools give uncertain or inconclusive results (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized). High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie; and Foldetta is uncertain. Consequently, the overall evidence leans toward a pathogenic effect, with no ClinVar record to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-9.342	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.0	1.99	Ambiguous	1.37	Ambiguous	0.86	Ambiguous	0.246	Likely Benign	-1.84	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.25	Benign	0.05	Affected			0.0746	0.3482		4	2	-1.9	18.03
c.1256A>C	E419A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-10.951	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.1	0.94	Ambiguous	0.75	Ambiguous	0.28	Likely Benign	0.398	Likely Benign	-5.60	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.32	Benign	0.03	Affected			0.4051	0.6705		0	-1	5.3	-58.04
c.3023A>T	D1008V 2D AIThe SynGAP1 D1008V variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, 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, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy assessments do not overturn this trend. Therefore, 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.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625											-4.828	Likely Benign	0.944	Likely Pathogenic	Ambiguous										0.242	Likely Benign	-3.61	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.64	Benign	0.01	Affected			0.1447	0.6608		-2	-3	7.7	-15.96
c.3529G>A	E1177K 2D AISynGAP1 missense variant E1177K is listed in ClinVar with an Uncertain significance status and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments give AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign effect, which does not contradict the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.566503	Binding	0.542	0.705	0.250					Uncertain		1				-3.413	Likely Benign	0.944	Likely Pathogenic	Ambiguous										0.560	Likely Pathogenic	-1.75	Neutral	0.905	Possibly Damaging	0.637	Possibly Damaging	5.44	Benign	0.11	Tolerated	4.32	2	0.1471	0.4424		0	1	-0.4	-0.94
c.3583G>A	V1195M 2D AIThe SynGAP1 V1195M missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools split evenly: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come 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 are mixed: AlphaMissense‑Optimized is “Uncertain,” SGM‑Consensus (majority vote) is benign, and Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the SGM‑Consensus and the balance of individual predictors—leans toward a benign effect. 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	Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250											-3.564	Likely Benign	0.944	Likely Pathogenic	Ambiguous										0.409	Likely Benign	-1.01	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	5.46	Benign	0.04	Affected			0.0589	0.3421		2	1	-2.3	32.06
c.859G>A	D287N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D287N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default). Two tools give uncertain results (Rosetta, AlphaMissense‑Optimized). High‑accuracy assessments further separate the evidence: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign impact. Overall, the majority of conventional predictors lean toward pathogenicity, while the most accurate stability‑based method suggests benign. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000											-10.167	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.16	Likely Benign	0.3	-0.54	Ambiguous	-0.19	Likely Benign	0.05	Likely Benign	0.372	Likely Benign	-4.60	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.06	Tolerated			0.1338	0.8194		2	1	0.0	-0.98
c.1012G>T	D338Y 2D AIThe SynGAP1 D338Y missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree on a deleterious effect: premPS is the sole predictor labeling it benign, whereas the remaining seven tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—classify it as pathogenic. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, AlphaMissense‑Optimized remains uncertain, and Foldetta is also uncertain. Overall, the preponderance of evidence indicates that D338Y is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-14.190	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	1.10	Ambiguous	1.3	0.91	Ambiguous	1.01	Ambiguous	0.22	Likely Benign	0.552	Likely Pathogenic	-6.49	Deleterious	0.989	Probably Damaging	0.832	Possibly Damaging	1.66	Pathogenic	0.00	Affected			0.0687	0.5609		-4	-3	2.2	48.09
c.1021G>C	G341R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G341R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, polyPhen‑2 HumVar, and Foldetta. Those that predict a pathogenic effect are SGM‑Consensus (Likely Pathogenic), polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show that the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts a likely pathogenic outcome, while Foldetta predicts a benign effect; AlphaMissense‑Optimized remains inconclusive. Overall, the majority of predictions lean toward a benign impact, and this does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign, though the evidence is not definitive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250											-8.263	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.28	Likely Benign	0.2	-1.25	Ambiguous	-0.49	Likely Benign	0.18	Likely Benign	0.379	Likely Benign	-1.03	Neutral	0.801	Possibly Damaging	0.417	Benign	0.34	Pathogenic	0.17	Tolerated			0.0838	0.3618		-3	-2	-4.1	99.14
c.1751T>G	I584S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I584S missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on pathogenicity include SGM‑Consensus, 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 show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as pathogenic. No contradictory evidence is present. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not conflict with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000											-13.379	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	3.15	Destabilizing	0.1	2.53	Destabilizing	2.84	Destabilizing	1.70	Destabilizing	0.710	Likely Pathogenic	-5.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.18	Pathogenic	0.03	Affected			0.2391	0.0858		-1	-2	-5.3	-26.08
c.200T>C	L67P 2D AIThe SynGAP1 missense variant L67P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact. 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		0.458154	Structured	0.473668	Uncertain	0.428	0.761	0.125											-2.852	Likely Benign	0.945	Likely Pathogenic	Ambiguous										0.150	Likely Benign	-0.80	Neutral	0.943	Possibly Damaging	0.766	Possibly Damaging	4.07	Benign	0.00	Affected			0.3052	0.1382		-3	-3	-5.4	-16.04
c.2093A>T	E698V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E698V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Tools with inconclusive results are FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports an uncertain result. Overall, the majority of evidence points to a pathogenic impact for E698V, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-12.797	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.76	Ambiguous	0.0	0.39	Likely Benign	0.58	Ambiguous	0.26	Likely Benign	0.480	Likely Benign	-6.51	Deleterious	0.992	Probably Damaging	0.967	Probably Damaging	3.33	Benign	0.00	Affected			0.0577	0.4546		-2	-2	7.7	-29.98
c.2183C>A	P728H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, all of which predict a deleterious impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the majority of evidence points to a pathogenic effect for P728H, and this conclusion does not contradict any ClinVar status because the variant is not yet classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-8.897	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	0.94	Ambiguous	0.0	0.86	Ambiguous	0.90	Ambiguous	0.64	Ambiguous	0.402	Likely Benign	-7.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1993	0.3016		0	-2	-1.6	40.02
c.2618G>T	S873I 2D AIThe SynGAP1 missense variant S873I has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of other in‑silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. High‑accuracy assessment therefore points to a Likely Pathogenic status from SGM‑Consensus, with AlphaMissense‑Optimized inconclusive and Foldetta missing. Overall, the preponderance of evidence suggests the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-9.412	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.305	Likely Benign	-3.44	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.02	Affected			0.1012	0.5560		-1	-2	5.3	26.08
c.2728G>C	G910R 2D AIThe SynGAP1 missense variant G910R is not 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, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because no ClinVar assertion exists. 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		0.762850	Disordered	0.707319	Binding	0.264	0.917	0.250											-4.566	Likely Benign	0.945	Likely Pathogenic	Ambiguous										0.235	Likely Benign	-1.78	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.86	Benign	0.02	Affected			0.0875	0.4198		-3	-2	-4.1	99.14
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	-1.64	Neutral	1.000	Probably Damaging	0.985	Probably Damaging	3.75	Benign	0.00	Affected			0.1961	0.2868		1	-1	-3.1	58.04
c.3613C>A	L1205M 2D AIThe SynGAP1 missense variant L1205M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-9.793	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.231	Likely Benign	-1.73	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0627	0.2297		4	2	-1.9	18.03
c.3664A>T	R1222W 2D AIThe SynGAP1 missense variant R1222W is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized yields an Uncertain result and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1222W. This conclusion is not contradicted by ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.933	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.260	Likely Benign	-6.00	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.03	Affected			0.0964	0.2761		2	-3	3.6	30.03
c.3728A>C	Q1243P 2D AIThe SynGAP1 missense variant Q1243P has no ClinVar record and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are unavailable. With five tools favoring pathogenicity versus three favoring benign, the overall evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Thus, based on the available predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.545602	Disordered	0.433693	Uncertain	0.887	0.551	0.500											-12.872	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-2.31	Neutral	0.969	Probably Damaging	0.715	Possibly Damaging	2.65	Benign	0.05	Affected			0.1624	0.3607		0	-1	1.9	-31.01
c.481C>T	P161S 2D AIThe SynGAP1 missense variant P161S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). 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											-8.550	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.085	Likely Benign	-3.63	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.94	Benign	0.00	Affected			0.3628	0.4597		1	-1	0.8	-10.04
c.782A>G	D261G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D261G is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include premPS and FATHMM, while the remaining tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-10.847	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous	2.81	Destabilizing	0.5	2.96	Destabilizing	2.89	Destabilizing	0.21	Likely Benign	0.850	Likely Pathogenic	-4.77	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	5.81	Benign	0.02	Affected			0.2924	0.4562		1	-1	3.1	-58.04
c.1334A>T	E445V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E445V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points toward a pathogenic effect. The variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-14.830	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.34	Likely Benign	0.1	-0.67	Ambiguous	-0.17	Likely Benign	0.32	Likely Benign	0.572	Likely Pathogenic	-6.68	Deleterious	0.992	Probably Damaging	0.967	Probably Damaging	3.34	Benign	0.01	Affected			0.0414	0.5233		-2	-2	7.7	-29.98
c.1355T>G	V452G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V452G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. AlphaMissense‑Optimized remains uncertain. Overall, the preponderance of evidence indicates that V452G is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000											-13.410	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	3.70	Destabilizing	0.1	3.37	Destabilizing	3.54	Destabilizing	2.46	Destabilizing	0.570	Likely Pathogenic	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.17	Benign	0.00	Affected			0.1948	0.2567		-1	-3	-4.6	-42.08
c.1363C>G	L455V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L455V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas the remaining 11 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, 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	GAP	0.188120	Structured	0.310377	Uncertain	0.963	0.168	0.000											-12.773	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.89	Destabilizing	0.1	2.38	Destabilizing	2.64	Destabilizing	1.41	Destabilizing	0.276	Likely Benign	-2.83	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.29	Benign	0.02	Affected			0.1149	0.3056		2	1	0.4	-14.03
c.1459A>C	N487H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N487H has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) predict a pathogenic or likely pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from these tools contradicts the lack of ClinVar annotation. Overall, the preponderance of pathogenic predictions indicates that the variant is most likely pathogenic, 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	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-11.403	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	1.15	Ambiguous	0.1	0.84	Ambiguous	1.00	Ambiguous	0.72	Ambiguous	0.548	Likely Pathogenic	-4.97	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.00	Affected			0.1123	0.3411		2	1	0.3	23.04
c.1484A>C	E495A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E495A missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include FoldX, while the remaining evaluated algorithms (REVEL, SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. No contradictory evidence is present from ClinVar or population databases. Overall, the preponderance of predictions supports a pathogenic classification for this variant. 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											-9.229	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.42	Likely Benign	0.1	0.85	Ambiguous	0.64	Ambiguous	0.69	Ambiguous	0.834	Likely Pathogenic	-5.84	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.38	Pathogenic	0.01	Affected			0.2711	0.4259		0	-1	5.3	-58.04
c.149T>G	I50S 2D AIThe SynGAP1 I50S missense variant 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, and FATHMM all classify it as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic impact. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments therefore point to a benign outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is likely benign, and Foldetta data are missing. 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		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-4.257	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-2.03	Neutral	0.334	Benign	0.099	Benign	3.74	Benign	0.00	Affected			0.2626	0.0800		-1	-2	-5.3	-26.08
c.1639T>A	C547S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547S is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-11.888	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.73	Ambiguous	1.29	Ambiguous	1.76	Destabilizing	0.884	Likely Pathogenic	-9.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.27	Pathogenic	0.04	Affected			0.4542	0.1792		0	-1	-3.3	-16.06
c.1640G>C	C547S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C547S is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.007912	Uncertain	0.971	0.275	0.000											-11.888	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.73	Ambiguous	1.29	Ambiguous	1.76	Destabilizing	0.825	Likely Pathogenic	-9.64	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.27	Pathogenic	0.04	Affected			0.4542	0.1792		0	-1	-3.3	-16.06
c.1703T>C	V568A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V568A missense variant is not reported in ClinVar (ClinVar status: none) but is present in the gnomAD database (gnomAD ID: 6‑33440755‑T‑C). Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools predict a pathogenic impact: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the consensus from high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.053503	Uncertain	0.937	0.257	0.000								6-33440755-T-C	2	1.25e-6	-10.929	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	1.90	Ambiguous	0.1	1.77	Ambiguous	1.84	Ambiguous	2.16	Destabilizing	0.834	Likely Pathogenic	-3.82	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	-1.38	Pathogenic	0.06	Tolerated	3.37	35	0.2413	0.1961		0	0	-2.4	-28.05
c.1877T>C	I626T 2D AISynGAP1 missense variant I626T is listed in ClinVar with an uncertain significance (ClinVar ID 3359331.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions are returned by REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only FATHMM predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Overall, the consensus of the majority of tools points to a pathogenic effect, contradicting the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000					Uncertain		1				-10.420	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.94	Destabilizing	0.1	2.70	Destabilizing	2.82	Destabilizing	2.23	Destabilizing	0.640	Likely Pathogenic	-4.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.04	Benign	0.00	Affected			0.1000	0.0840		0	-1	-5.2	-12.05
c.1900G>A	A634T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634T is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, while only FATHMM predicts benign. Two tools give uncertain results: AlphaMissense‑Optimized and Foldetta. High‑accuracy assessment shows that the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) supports a pathogenic classification, whereas AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for A634T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000											-12.451	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.56	Destabilizing	0.1	1.11	Ambiguous	1.84	Ambiguous	1.34	Destabilizing	0.603	Likely Pathogenic	-3.98	Deleterious	0.994	Probably Damaging	0.986	Probably Damaging	2.51	Benign	0.01	Affected			0.1397	0.5240		1	0	-2.5	30.03
c.1996G>A	E666K 2D AIThe SynGAP1 missense variant E666K is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of predictions lean toward pathogenicity, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-11.367	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	0.20	Likely Benign	0.6	0.30	Likely Benign	0.25	Likely Benign	0.43	Likely Benign	0.401	Likely Benign	-3.26	Deleterious	0.992	Probably Damaging	0.717	Possibly Damaging	3.46	Benign	0.05	Affected			0.2953	0.5300		0	1	-0.4	-0.94
c.2135G>A	G712D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G712D is catalogued in gnomAD (ID 6‑33441600‑G‑A) but has no ClinVar entry. In silico predictors show mixed results: benign calls come from REVEL, SIFT, and FATHMM, while pathogenic calls are made by FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain predictions are reported by premPS and AlphaMissense‑Optimized. The high‑accuracy consensus tools give a pathogenic verdict: AlphaMissense‑Optimized is inconclusive, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Overall, the majority of reliable predictors and the consensus methods lean toward a pathogenic effect, and this assessment does not conflict with ClinVar, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000								6-33441600-G-A	1	6.20e-7	-8.211	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.87	Destabilizing	0.1	5.37	Destabilizing	4.12	Destabilizing	0.90	Ambiguous	0.320	Likely Benign	-5.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.67	Benign	0.12	Tolerated	3.50	9	0.2146	0.2533		-1	1	-3.1	58.04
c.2158G>T	D720Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D720Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and premPS, while pathogenic predictions are made by SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive. The high‑accuracy consensus (SGM Consensus) classifies the variant as Likely Pathogenic, and Foldetta likewise yields an uncertain stability change. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-14.771	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	-0.74	Ambiguous	0.1	-1.38	Ambiguous	-1.06	Ambiguous	0.20	Likely Benign	0.499	Likely Benign	-7.05	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.0626	0.5973		-4	-3	2.2	48.09
c.3388A>G	K1130E 2D AIThe SynGAP1 missense variant K1130E is not 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. Those 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) yields a Likely Benign classification, while AlphaMissense‑Optimized remains Uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools and the SGM consensus support a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.998	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.422	Likely Benign	-1.23	Neutral	0.649	Possibly Damaging	0.266	Benign	5.45	Benign	0.00	Affected			0.4251	0.1876		0	1	0.4	0.94
c.3390G>C	K1130N 2D AIThe SynGAP1 missense variant K1130N is not 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 it 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 Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. 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. Thus, based on current computational predictions, the K1130N variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.822	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-1.02	Neutral	0.818	Possibly Damaging	0.287	Benign	5.43	Benign	0.00	Affected			0.4119	0.2393		1	0	0.4	-14.07
c.3390G>T	K1130N 2D AIThe SynGAP1 missense variant K1130N is not 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 it 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 Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. 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. Thus, based on current computational predictions, the K1130N variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.822	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-1.02	Neutral	0.818	Possibly Damaging	0.287	Benign	5.43	Benign	0.00	Affected			0.4119	0.2393		1	0	0.4	-14.07
c.3584T>A	V1195E 2D AIThe SynGAP1 missense variant V1195E 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, reports a likely benign classification. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the balance of evidence leans toward a benign impact, with no conflict with ClinVar status (which has no entry). 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	Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250											-1.722	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.499	Likely Benign	-2.19	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	5.64	Benign	0.02	Affected			0.0870	0.1268		-2	-2	-7.7	29.98
c.3818T>G	L1273R 2D AIThe SynGAP1 missense variant L1273R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment is not contradicted by any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500											-6.252	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.431	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.934	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1369	0.0761		-3	-2	-8.3	43.03
c.3991A>T	I1331F 2D AIThe SynGAP1 missense variant I1331F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-4.220	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.46	Neutral	0.984	Probably Damaging	0.969	Probably Damaging	3.31	Benign	0.00	Affected			0.0522	0.3225		1	0	-1.7	34.02
c.1914G>C	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1914G>T	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1934T>C	F645S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F645S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while both the SGM Consensus and Foldetta predict pathogenicity. No evidence from ClinVar contradicts these findings. Overall, the preponderance of predictions supports a pathogenic classification for F645S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.276445	Uncertain	0.921	0.325	0.000											-9.748	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	2.49	Destabilizing	0.2	2.30	Destabilizing	2.40	Destabilizing	1.57	Destabilizing	0.326	Likely Benign	-5.34	Deleterious	0.755	Possibly Damaging	0.112	Benign	3.37	Benign	0.03	Affected			0.3899	0.0547		-3	-2	-3.6	-60.10
c.2158G>C	D720H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720H missense variant is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and is labeled Likely Pathogenic. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, indicates a Benign effect. Considering the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125											-12.355	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	-0.87	Ambiguous	-0.42	Likely Benign	0.48	Likely Benign	0.444	Likely Benign	-5.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.13	Pathogenic	0.01	Affected			0.1363	0.6198		1	-1	0.3	22.05
c.239A>T	K80I 2D AIThe SynGAP1 missense variant K80I is not 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, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal split between benign and pathogenic signals and no ClinVar entry to contradict the computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.320	Likely Benign	0.947	Likely Pathogenic	Ambiguous										0.083	Likely Benign	-2.54	Deleterious	0.939	Possibly Damaging	0.164	Benign	3.86	Benign	0.00	Affected			0.1095	0.2981		-2	-3	8.4	-15.01
c.3565G>A	E1189K 2D AIThe SynGAP1 missense variant E1189K is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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—five benign predictions versus three pathogenic ones, a consensus benign rating, and no conflicting ClinVar annotation—suggests that E1189K is most likely benign. 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	Coiled-coil	0.562014	Disordered	0.466885	Uncertain	0.704	0.623	0.625											-5.565	Likely Benign	0.947	Likely Pathogenic	Ambiguous										0.423	Likely Benign	-1.64	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.37	Benign	0.08	Tolerated			0.1597	0.4046		0	1	-0.4	-0.94
c.3596A>G	E1199G 2D AIThe SynGAP1 missense change E1199G is not reported in ClinVar (ClinVar ID = None) and has no entries in gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for E1199G, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-13.414	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous										0.360	Likely Benign	-5.08	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.45	Pathogenic	0.00	Affected			0.2461	0.3960		0	-2	3.1	-72.06
c.3604A>G	I1202V 2D AIThe SynGAP1 I1202V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. 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 (five pathogenic vs. three benign predictions) points to a likely pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-5.494	Likely Benign	0.947	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-0.80	Neutral	0.958	Probably Damaging	0.970	Probably Damaging	2.00	Pathogenic	0.05	Affected			0.1109	0.2697		4	3	-0.3	-14.03
c.700C>T	R234W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R234W missense variant is listed in ClinVar (ID 856396.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33435551‑C‑T). Prediction tools that agree on a benign effect include premPS and FATHMM, whereas the majority of other in‑silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) indicate a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain”; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is “Uncertain.” Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar designation of uncertainty rather than a benign classification. 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					Uncertain		1	6-33435551-C-T	3	1.86e-6	-12.625	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.96	Ambiguous	0.3	0.69	Ambiguous	0.83	Ambiguous	0.13	Likely Benign	0.805	Likely Pathogenic	-5.52	Deleterious	0.997	Probably Damaging	0.803	Possibly Damaging	5.76	Benign	0.01	Affected	3.40	14	0.1302	0.4035		2	-3	3.6	30.03	262.8	39.6	-0.1	0.0	-0.2	0.2		X						Potentially Pathogenic	The guanidinium group of Arg234, located in a β-α loop between an anti-parallel β sheet strand (residues Gly227-Phe231) and an α helix (res. Ala236-Val250), forms a salt bridge with the carboxylate group of Glu238 in the α helix. Occasionally, it also bonds with the GAP domain residues Ser678 and Glu680. Thus, the positively charged Arg234 could contribute to the tertiary structure assembly between the PH and GAP domains. In contrast, the indole side chain of Trp234 in the variant is located on the protein surface in the variant simulations and is unable to form any interactions.
c.746C>G	A249G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A249G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Only FATHMM predicts a benign outcome. Uncertain results are reported by FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show SGM‑Consensus as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence supports a pathogenic classification for A249G, and this conclusion does not conflict with ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.505461	Disordered	0.255452	Uncertain	0.810	0.336	0.125											-9.678	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	1.04	Ambiguous	0.2	2.02	Destabilizing	1.53	Ambiguous	1.19	Destabilizing	0.607	Likely Pathogenic	-2.97	Deleterious	0.990	Probably Damaging	0.760	Possibly Damaging	5.59	Benign	0.04	Affected			0.1667	0.2675		1	0	-2.2	-14.03
c.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	3.23	Destabilizing	0.8	5.73	Destabilizing	4.48	Destabilizing	0.43	Likely Benign	0.250	Likely Benign	-4.22	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.69	Pathogenic	0.09	Tolerated			0.1866	0.4497		0	-2	2.9	-59.07
c.1385A>C	K462T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K462T missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-11.586	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	1.08	Ambiguous	0.82	Ambiguous	0.30	Likely Benign	0.414	Likely Benign	-5.82	Deleterious	0.999	Probably Damaging	1.000	Probably Damaging	3.47	Benign	0.08	Tolerated			0.2095	0.3257		0	-1	3.2	-27.07
c.1454G>A	R485H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R485H missense variant is listed in ClinVar as Benign (ClinVar ID 3707943.0) and is present in the gnomAD database (gnomAD ID 6‑33438486‑G‑A). Functional prediction tools that agree on a benign effect are Rosetta and Foldetta, while the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the ClinVar benign 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					Likely Benign		1	6-33438486-G-A	13	8.05e-6	-13.628	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.77	Ambiguous	0.1	0.12	Likely Benign	0.45	Likely Benign	1.13	Destabilizing	0.618	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.93	Pathogenic	0.00	Affected	3.37	35	0.2990	0.1602		0	2	1.3	-19.05
c.145T>C	C49R 2D AIThe SynGAP1 missense variant C49R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain and no Foldetta (FoldX‑MD/Rosetta) result is available. Taken together, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-10.000	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.320	Likely Benign	-3.53	Deleterious	0.676	Possibly Damaging	0.761	Possibly Damaging	3.95	Benign	0.00	Affected			0.1605	0.2120		-4	-3	-7.0	53.05
c.1490A>G	Y497C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497C is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all return a deleterious signal: 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) all predict pathogenic. No tool reports a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM Consensus as “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) as “Pathogenic.” Overall, the variant is most likely pathogenic based on the consensus of predictive algorithms, which contradicts the current ClinVar “Uncertain” classification. 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					Uncertain		1				-11.872	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	3.88	Destabilizing	0.1	4.76	Destabilizing	4.32	Destabilizing	1.40	Destabilizing	0.806	Likely Pathogenic	-8.82	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	-1.65	Pathogenic	0.03	Affected	3.37	35	0.2905	0.1488		0	-2	3.8	-60.04	209.9	59.1	-0.1	0.0	-0.3	0.1		X					X	Potentially Pathogenic	Tyr497 is located in the α-helix (res. Leu489-Glu519) within the inter-helix space of four α-helices (res. Leu489-Ile501, res. Val441-Ser457, res. Arg563-Glu578, res. Ala461-Val473). In the WT simulations, the phenol ring of Tyr497 hydrophobically packs with other residues in the inter-helix space (e.g., Leu465, Leu565, Val568). The hydroxyl group of Tyr497 also alternately forms hydrogen bonds with the carboxylate side chain of Gln456 and the backbone carbonyl of Glu564. Thus, Tyr497 plays a role in the folding and maintenance of the tertiary structure assembly between these four helices.In the variant simulations, the comparatively smaller residue, Cys497, cannot maintain any of the interactions seen with Tyr497 in the WT. Although no severe deleterious consequences are observed in the simulations, the structural effects could be more pronounced during actual protein folding. Indeed, the tertiary structure is seen to slightly break apart in the variant simulations.
c.1735C>G	R579G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R579G is reported in gnomAD (ID 6‑33440787‑C‑G) and has no ClinVar entry. Prediction tools that assess pathogenicity uniformly favor a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenic. No tool in the dataset reports a benign outcome; the only uncertain calls are from FoldX, AlphaMissense‑Optimized, and Foldetta. High‑accuracy assessments further support pathogenicity: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic, while AlphaMissense‑Optimized and Foldetta remain uncertain. Consequently, the collective evidence indicates that R579G is most likely pathogenic, 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	GAP	0.053060	Structured	0.022872	Uncertain	0.877	0.244	0.000								6-33440787-C-G	1	6.20e-7	-14.298	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	1.43	Ambiguous	0.0	2.36	Destabilizing	1.90	Ambiguous	1.32	Destabilizing	0.680	Likely Pathogenic	-5.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.40	Pathogenic	0.01	Affected	3.37	34	0.3078	0.2554		-2	-3	4.1	-99.14
c.1804A>T	I602F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I602F missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign outcome. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Taken together, the overwhelming majority of evidence points to a pathogenic effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-13.974	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	2.47	Destabilizing	1.1	-0.61	Ambiguous	0.93	Ambiguous	0.87	Ambiguous	0.822	Likely Pathogenic	-3.98	Deleterious	0.999	Probably Damaging	0.937	Probably Damaging	-1.82	Pathogenic	0.00	Affected			0.0708	0.2343		1	0	-1.7	34.02
c.1805T>C	I602T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I602T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify it as pathogenic or likely pathogenic. No tool reports a benign outcome. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. Consequently, the variant is most likely pathogenic according to the available computational evidence, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.010221	Structured	0.186541	Uncertain	0.963	0.171	0.000											-12.238	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	2.39	Destabilizing	0.1	2.14	Destabilizing	2.27	Destabilizing	1.94	Destabilizing	0.931	Likely Pathogenic	-4.82	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	-2.00	Pathogenic	0.00	Affected			0.0890	0.0989		0	-1	-5.2	-12.05
c.1819C>T	L607F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607F is catalogued in gnomAD (6‑33440871‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all report pathogenic or likely pathogenic. Only FoldX predicts a benign outcome, while Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as likely pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L607F, and this conclusion is not contradicted by ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000								6-33440871-C-T	1	6.19e-7	-13.654	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	1.20	Ambiguous	0.72	Ambiguous	0.61	Ambiguous	0.758	Likely Pathogenic	-3.98	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	-1.54	Pathogenic	0.01	Affected	3.37	35	0.0872	0.2816		0	2	-1.0	34.02
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	0.53	Ambiguous	0.1	0.30	Likely Benign	0.42	Likely Benign	0.28	Likely Benign	0.484	Likely Benign	-5.88	Deleterious	0.872	Possibly Damaging	0.839	Possibly Damaging	2.86	Benign	0.00	Affected	3.37	31	0.1899	0.3270		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.2786A>G	N929S 2D AIThe SynGAP1 missense variant N929S is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a consensus toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, FATHMM, and AlphaMissense‑Default all predict a deleterious effect, while REVEL uniquely predicts a benign outcome. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a damaging interpretation: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain; Foldetta data are unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for N929S. This conclusion does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-7.100	In-Between	0.948	Likely Pathogenic	Ambiguous										0.249	Likely Benign	-3.89	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.4117	0.7639		1	1	2.7	-27.03
c.319A>G	R107G 2D AIThe SynGAP1 missense variant R107G is not 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, and FATHMM, while those that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a tie and thus unavailable, and Foldetta stability analysis is missing. Overall, the majority of tools (five benign vs. three pathogenic) suggest a benign impact, but the lack of consensus from the most accurate predictors means the variant’s effect remains uncertain. 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.			0.666105	Disordered	0.663448	Binding	0.331	0.863	0.875											-3.486	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-3.15	Deleterious	0.421	Benign	0.050	Benign	2.98	Benign	0.00	Affected			0.3280	0.4000		-3	-2	4.1	-99.14
c.3643A>C	K1215Q 2D AIThe SynGAP1 missense variant K1215Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and PROVEAN, whereas the remaining tools—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for K1215Q, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-9.763	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.099	Likely Benign	-2.23	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.02	Affected			0.4002	0.0856		1	1	0.4	-0.04
c.376T>C	F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status, which contains no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.992	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.091	Likely Benign	-2.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.00	Affected			0.2780	0.3399		2	0	1.0	-34.02
c.378C>A	F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the ClinVar status, which contains no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.992	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.114	Likely Benign	-2.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.00	Affected			0.2780	0.3399		2	0	1.0	-34.02
c.378C>G	F126L 2D AIThe SynGAP1 missense variant F126L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, while the high‑accuracy AlphaMissense‑Optimized result is inconclusive and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact; the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.712056	Binding	0.316	0.874	0.500											-0.992	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.114	Likely Benign	-2.27	Neutral	0.001	Benign	0.001	Benign	4.01	Benign	0.00	Affected			0.2780	0.3399		2	0	1.0	-34.02
c.3995C>T	T1332M 2D AISynGAP1 missense variant T1332M is listed as Benign in ClinVar (ID 794425) and is present in gnomAD (6‑33451869‑C‑T). Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized returned an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and no Foldetta stability data are available. Overall, the majority of evidence points toward a pathogenic effect, which contradicts the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.948427	Binding	0.442	0.754	0.875					Likely Benign		1	6-33451869-C-T	20	1.86e-5	-4.107	Likely Benign	0.948	Likely Pathogenic	Ambiguous										0.252	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	2.95	Benign	0.00	Affected	3.77	5	0.1551	0.6513		-1	-1	2.6	30.09
c.532A>C	K178Q 2D AIThe SynGAP1 K178Q missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, 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 consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-9.779	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.197	Likely Benign	-2.57	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.88	Benign	0.01	Affected			0.5170	0.1216	Weaken	1	1	0.4	-0.04
c.653T>G	F218C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218C is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33435295‑T‑G). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools (REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. Results that are uncertain or unavailable are FoldX, ESM1b, AlphaMissense‑Optimized, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic prediction (2 pathogenic vs. 1 benign votes); and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for F218C, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000								6-33435295-T-G	1	6.20e-7	-7.234	In-Between	0.948	Likely Pathogenic	Ambiguous	1.49	Ambiguous	0.1	2.20	Destabilizing	1.85	Ambiguous	1.02	Destabilizing	0.744	Likely Pathogenic	-4.92	Deleterious	0.994	Probably Damaging	0.667	Possibly Damaging	5.78	Benign	0.03	Affected	3.41	13	0.2330	0.1321		-2	-4	-0.3	-44.04
c.1370G>A	S457N 2D AIThe SynGAP1 missense variant S457N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, Rosetta, SIFT, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give a mixed picture: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) favors pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign effect. Overall, the majority of individual predictors lean toward pathogenicity, but the high‑accuracy Foldetta result suggests a benign impact. Thus, the variant is most likely pathogenic based on the preponderance of predictions, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000					Uncertain		1				-10.221	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.0	-0.22	Likely Benign	-0.02	Likely Benign	0.67	Ambiguous	0.241	Likely Benign	-2.76	Deleterious	0.940	Possibly Damaging	0.843	Possibly Damaging	3.28	Benign	0.06	Tolerated			0.1015	0.4980		1	1	-2.7	27.03
c.146G>A	C49Y 2D AIThe SynGAP1 missense variant C49Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for C49Y. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-11.097	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous										0.312	Likely Benign	-3.38	Deleterious	0.676	Possibly Damaging	0.761	Possibly Damaging	3.85	Benign	0.00	Affected			0.1016	0.3172		0	-2	-3.8	60.04
c.149T>C	I50T 2D AIThe SynGAP1 missense variant I50T is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree that the change is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM all classify it as benign. In contrast, SIFT and AlphaMissense‑Default predict a pathogenic effect. 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. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments therefore point to a benign outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is benign, and Foldetta data are missing. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-5.121	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-1.61	Neutral	0.092	Benign	0.037	Benign	3.76	Benign	0.00	Affected			0.0950	0.0708		0	-1	-5.2	-12.05
c.1552T>A	Y518N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y518N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Foldetta) uniformly predict a pathogenic impact. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta also predicts pathogenicity. Taken together, the overwhelming majority of evidence indicates a pathogenic effect. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.036	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	2.99	Destabilizing	0.8	1.50	Ambiguous	2.25	Destabilizing	1.29	Destabilizing	0.506	Likely Pathogenic	-8.45	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.04	Affected			0.1791	0.0212		-2	-2	-2.2	-49.07
c.1689G>C	R563S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R563S missense change is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Five tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) return uncertain or inconclusive results. High‑accuracy assessments are likewise ambiguous: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑to‑2 tie and therefore unavailable; Foldetta also reports an uncertain stability change. Consequently, the evidence does not strongly support either benign or pathogenic status. The variant’s classification is therefore inconclusive and does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-6.503	Likely Benign	0.949	Likely Pathogenic	Ambiguous	1.16	Ambiguous	0.1	1.46	Ambiguous	1.31	Ambiguous	0.69	Ambiguous	0.251	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.23	Tolerated			0.3031	0.2534		0	-1	3.7	-69.11
c.1689G>T	R563S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R563S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—yield uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑to‑2 tie, and Foldetta is uncertain. Consequently, the evidence does not strongly favor either outcome. Based on the current predictions, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-6.503	Likely Benign	0.949	Likely Pathogenic	Ambiguous	1.16	Ambiguous	0.1	1.46	Ambiguous	1.31	Ambiguous	0.69	Ambiguous	0.251	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.23	Tolerated			0.3031	0.2534		0	-1	3.7	-69.11
c.1795T>G	C599G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the evidence strongly favors a pathogenic effect, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.342	Likely Pathogenic	0.949	Likely Pathogenic	Ambiguous	1.40	Ambiguous	0.0	0.90	Ambiguous	1.15	Ambiguous	1.43	Destabilizing	0.923	Likely Pathogenic	-11.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.50	Pathogenic	0.03	Affected			0.2444	0.2130		-3	-3	-2.9	-46.09
c.2285A>T	D762V 2D AIThe SynGAP1 D762V missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returned 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 there is no ClinVar entry 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.			0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-6.122	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.229	Likely Benign	-1.98	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.08	Pathogenic	0.01	Affected			0.1105	0.8785		-2	-3	7.7	-15.96
c.3028T>C	F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized is currently uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-1.982	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.099	Likely Benign	-1.51	Neutral	0.910	Possibly Damaging	0.468	Possibly Damaging	2.75	Benign	0.62	Tolerated			0.2538	0.3245		2	0	1.0	-34.02
c.3030T>A	F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, and AlphaMissense‑Optimized is currently uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-1.982	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-1.51	Neutral	0.910	Possibly Damaging	0.468	Possibly Damaging	2.75	Benign	0.62	Tolerated			0.2538	0.3245		2	0	1.0	-34.02
c.3030T>G	F1010L 2D AIThe SynGAP1 missense variant F1010L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign classification, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for F1010L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.912572	Binding	0.286	0.881	0.625											-1.982	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.142	Likely Benign	-1.51	Neutral	0.910	Possibly Damaging	0.468	Possibly Damaging	2.75	Benign	0.62	Tolerated			0.2538	0.3245		2	0	1.0	-34.02
c.3118G>C	G1040R 2D AIThe SynGAP1 missense variant G1040R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to polyPhen‑2 HumVar and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the majority of evidence supports a pathogenic classification, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-2.901	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.704	Likely Pathogenic	-3.00	Deleterious	0.463	Possibly Damaging	0.194	Benign	-0.74	Pathogenic	0.00	Affected			0.0924	0.4415		-3	-2	-4.1	99.14
c.3487C>G	H1163D 2D AISynGAP1 missense variant H1163D is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized rates the variant as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie and is therefore unavailable, and Foldetta folding‑stability analysis is not provided. With an equal number of benign and pathogenic predictions and no decisive high‑accuracy evidence, the variant remains ambiguous. Thus, it is most likely neither clearly benign nor pathogenic, and this uncertainty aligns with its ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.858469	Binding	0.328	0.825	0.375					Uncertain		1				-2.107	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.476	Likely Benign	-2.60	Deleterious	0.991	Probably Damaging	0.991	Probably Damaging	5.44	Benign	0.31	Tolerated	3.88	3	0.2145	0.1986		1	-1	-0.3	-22.05
c.536A>G	E179G 2D AIThe SynGAP1 missense variant E179G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Among the available in‑silico predictors, six tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM) unanimously predict a benign effect, whereas two tools (PROVEAN and AlphaMissense‑Default) predict pathogenicity. High‑accuracy predictors give no definitive verdict: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes); and Foldetta results are unavailable. Consequently, the overall evidence leans toward a benign interpretation, with no conflict with 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.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-6.527	Likely Benign	0.949	Likely Pathogenic	Ambiguous										0.158	Likely Benign	-4.24	Deleterious	0.001	Benign	0.004	Benign	3.97	Benign	0.09	Tolerated			0.3273	0.6425		0	-2	3.1	-72.06
c.649G>C	E217Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E217Q is reported in gnomAD (ID 6‑33435291‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. With six benign versus three pathogenic calls and a benign consensus from the high‑accuracy panel, the variant is most likely benign. This conclusion does not contradict ClinVar, which contains no classification for this change. 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								6-33435291-G-C	1	6.20e-7	-6.810	Likely Benign	0.949	Likely Pathogenic	Ambiguous	0.25	Likely Benign	0.2	1.61	Ambiguous	0.93	Ambiguous	0.67	Ambiguous	0.459	Likely Benign	-1.89	Neutral	0.900	Possibly Damaging	0.461	Possibly Damaging	5.83	Benign	0.14	Tolerated	3.41	13	0.1474	0.8473		2	2	0.0	-0.98
c.935T>A	F312Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F312Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a deleterious effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default, all of which classify the change as pathogenic. No tool in the dataset predicts a benign outcome. High‑accuracy assessments show the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, while AlphaMissense‑Optimized and Foldetta provide uncertain results. Overall, the majority of evidence points to a pathogenic 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 Pathogenic	C2	0.225814	Structured	0.361163	Uncertain	0.915	0.317	0.000											-7.571	In-Between	0.949	Likely Pathogenic	Ambiguous	1.04	Ambiguous	0.1	0.89	Ambiguous	0.97	Ambiguous	0.99	Ambiguous	0.744	Likely Pathogenic	-2.76	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	1.21	Pathogenic	0.02	Affected			0.1443	0.2728		7	3	-4.1	16.00
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	0.51	Ambiguous	0.0	-0.15	Likely Benign	0.18	Likely Benign	0.46	Likely Benign	0.506	Likely Pathogenic	-4.82	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.96	Pathogenic	0.08	Tolerated			0.1839	0.3354		0	-1	3.2	-27.07
c.1058T>G	L353R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353R is not reported in ClinVar and is absent from gnomAD. In silico predictors largely agree on a deleterious effect: benign predictions are limited to REVEL, whereas the remaining tools—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)—all classify the variant as pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is uncertain, SGM‑Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction contradicts the ClinVar status, which is currently unreported. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-11.213	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	3.60	Destabilizing	0.5	2.48	Destabilizing	3.04	Destabilizing	1.91	Destabilizing	0.444	Likely Benign	-4.15	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.33	Pathogenic	0.01	Affected			0.1304	0.1145		-3	-2	-8.3	43.03
c.1280A>C	H427P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H427P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic impact. Two tools are uncertain: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as inconclusive, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate a pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification for H427P, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.394261	Uncertain	0.962	0.287	0.000											-11.098	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	4.74	Destabilizing	0.1	7.61	Destabilizing	6.18	Destabilizing	0.68	Ambiguous	0.324	Likely Benign	-4.22	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.51	Benign	0.01	Affected			0.2061	0.3442		0	-2	1.6	-40.02
c.1682T>A	F561Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) are uncertain or unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Based on the consensus of the majority of evidence‑based predictors, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000											-12.692	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	1.54	Ambiguous	0.1	0.75	Ambiguous	1.15	Ambiguous	1.28	Destabilizing	0.693	Likely Pathogenic	-2.99	Deleterious	0.988	Probably Damaging	0.976	Probably Damaging	-1.34	Pathogenic	0.01	Affected			0.1344	0.1120		7	3	-4.1	16.00
c.1787G>A	R596H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R596H is listed in ClinVar as benign (ClinVar ID 1989474.0) and is present in gnomAD (ID 6‑33440839‑G‑A). Functional prediction tools largely agree on a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus all report pathogenicity, while only Rosetta predicts a benign outcome. Two tools are inconclusive: AlphaMissense‑Optimized and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from the four pathogenic votes) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact, directly contradicting the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.017797	Structured	0.135423	Uncertain	0.918	0.134	0.000					Likely Benign		1	6-33440839-G-A	15	9.29e-6	-11.128	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	3.00	Destabilizing	0.9	0.43	Likely Benign	1.72	Ambiguous	1.35	Destabilizing	0.717	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.43	Pathogenic	0.00	Affected	3.37	35	0.3290	0.1208		2	0	1.3	-19.05	223.5	80.5	-0.1	0.0	-0.1	0.3		X		X				Potentially Pathogenic	The guanidinium group of Arg596, located in an α helix (res. Glu582-Met603), forms a salt bridge with the carboxylate group of Glu495 from another α helix (res. Leu489-Glu519). In the WT simulations, the side chain of Arg596 hydrogen bonds with the backbone carbonyl groups of Asn487, Glu486, Arg485, and Phe484. Additionally, Arg596 can hydrogen bond with the carboxamide group of the Asn487 side chain on an opposing loop that links two α helices (res. Ala461-Arg475, res. Leu489-Glu519).In the variant simulations, the imidazole ring of His596 can form hydrogen bonds with the same residues as arginine; however, these interactions are not as coordinated or strong in comparison. Thus, the residue swap could affect the tertiary structure assembly more profoundly than observed in the simulations. Notably, Arg596 plays a key role in positioning the aforementioned loop, which is crucial for the placement of the “arginine finger” or the Arg485 side chain during RasGTPase activation.
c.1961A>T	E654V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E654V missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, and FATHMM, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. Overall, the majority of tools (8 pathogenic vs. 4 benign) and the SGM‑Consensus result support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-12.306	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.55	Ambiguous	0.0	-0.33	Likely Benign	0.11	Likely Benign	0.21	Likely Benign	0.540	Likely Pathogenic	-6.66	Deleterious	0.988	Probably Damaging	0.734	Possibly Damaging	3.31	Benign	0.01	Affected			0.0686	0.4757		-2	-2	7.7	-29.98
c.2048T>G	I683S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. No prediction or folding stability result is missing or inconclusive; all available evidence points to a deleterious effect. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-11.443	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	2.53	Destabilizing	0.2	1.94	Ambiguous	2.24	Destabilizing	1.35	Destabilizing	0.552	Likely Pathogenic	-5.88	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.29	Benign	0.05	Affected			0.1936	0.1320		-1	-2	-5.3	-26.08
c.2183C>T	P728L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; FoldX and AlphaMissense‑Optimized are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from the unanimous pathogenic vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from standard and high‑accuracy predictors points to a pathogenic effect for P728L. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-11.125	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.0	0.15	Likely Benign	0.47	Likely Benign	0.20	Likely Benign	0.402	Likely Benign	-8.27	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.2321	0.4713		-3	-3	5.4	16.04
c.2335A>C	S779R 2D AIThe SynGAP1 missense variant S779R is not 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, and ESM1b, while those that predict a pathogenic effect are 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, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, 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.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.044	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.103	Likely Benign	-0.74	Neutral	0.846	Possibly Damaging	0.627	Possibly Damaging	2.29	Pathogenic	0.12	Tolerated			0.0961	0.4046		0	-1	-3.7	69.11
c.2337C>A	S779R 2D AIThe SynGAP1 missense variant S779R is not 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, and ESM1b, while those that predict a pathogenic effect are 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, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, 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.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.044	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.119	Likely Benign	-0.74	Neutral	0.846	Possibly Damaging	0.627	Possibly Damaging	2.29	Pathogenic	0.12	Tolerated			0.0961	0.4046		0	-1	-3.7	69.11
c.2337C>G	S779R 2D AIThe SynGAP1 missense variant S779R is not 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, and ESM1b, while those that predict a pathogenic effect are 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, is inconclusive because it yields a 2‑to‑2 split. High‑accuracy methods give mixed results: AlphaMissense‑Optimized is uncertain, and both the SGM Consensus and Foldetta (which would combine FoldX‑MD and Rosetta outputs) are unavailable. Consequently, the overall prediction is ambiguous. The variant is most likely benign based on the balance of evidence, 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.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.044	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-0.74	Neutral	0.846	Possibly Damaging	0.627	Possibly Damaging	2.29	Pathogenic	0.12	Tolerated			0.0961	0.4046		0	-1	-3.7	69.11
c.2428C>A	R810S 2D AIThe SynGAP1 R810S missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. The high‑accuracy consensus from SGM (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenicity, while the lack of a Foldetta result leaves that evidence inconclusive. Overall, the preponderance of pathogenic predictions suggests that R810S is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-5.996	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.204	Likely Benign	-3.20	Deleterious	0.996	Probably Damaging	0.900	Possibly Damaging	2.44	Pathogenic	0.01	Affected			0.3152	0.4556		0	-1	3.7	-69.11
c.2443C>A	R815S 2D AISynGAP1 R815S is listed in ClinVar as Benign (ID 3645150.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Two tools report uncertainty: ESM1b and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM Consensus as Benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the majority of predictions lean toward pathogenicity, whereas the consensus and high‑accuracy tools suggest benignity. Thus, the variant is most likely pathogenic based on the prevailing predictions, contradicting its ClinVar benign designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.394753	Structured	0.780568	Binding	0.278	0.907	0.250					Benign		1				-7.324	In-Between	0.950	Likely Pathogenic	Ambiguous										0.138	Likely Benign	-1.86	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.67	Benign	0.02	Affected			0.2937	0.4164		0	-1	3.7	-69.11
c.2471G>T	S824I 2D AIThe SynGAP1 missense variant S824I 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 SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the balance of evidence—five benign versus three pathogenic calls, a benign SGM‑Consensus, and no conflicting ClinVar annotation—suggests that the variant is most likely benign. This conclusion does not contradict any existing ClinVar status, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750											-6.799	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.60	Benign	0.11	Tolerated			0.1177	0.6045		-1	-2	5.3	26.08
c.2792T>C	L931P 2D AIThe SynGAP1 missense variant L931P is not reported in ClinVar and is absent from gnomAD. Prediction tools show a strong bias toward pathogenicity: SIFT, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Default all predict a deleterious effect, whereas only REVEL indicates a benign outcome. High‑accuracy assessments reinforce this trend: the SGM consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic, and AlphaMissense‑Optimized returns an uncertain result. Foldetta predictions are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for L931P, and this conclusion is consistent with the absence of any ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-8.624	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.376	Likely Benign	-3.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3203	0.1698		-3	-3	-5.4	-16.04
c.2956G>A	E986K 2D AIThe SynGAP1 missense variant E986K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and PROVEAN, while those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results and are not considered evidence for either side. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic verdict (2 pathogenic vs. 1 benign, 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 predictors classify the variant as pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750											-7.174	In-Between	0.950	Likely Pathogenic	Ambiguous										0.164	Likely Benign	-2.19	Neutral	0.924	Possibly Damaging	0.722	Possibly Damaging	2.15	Pathogenic	0.00	Affected			0.2760	0.7973		0	1	-0.4	-0.94
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	-2.30	Neutral	0.004	Benign	0.002	Benign	3.67	Benign	0.00	Affected			0.1941	0.4742		-1	-1	3.8	-55.08
c.3566A>T	E1189V 2D AIThe SynGAP1 E1189V missense change is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2). Foldetta stability predictions are not available. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy methods do not overturn this trend. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.466885	Uncertain	0.704	0.623	0.625											-5.048	Likely Benign	0.950	Likely Pathogenic	Ambiguous										0.492	Likely Benign	-3.50	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.26	Benign	0.02	Affected			0.0467	0.4252		-2	-2	7.7	-29.98
c.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	-3.29	Deleterious	0.888	Possibly Damaging	0.435	Benign	3.92	Benign	0.02	Affected			0.2093	0.2550		1	-1	-3.1	58.04
c.407G>A	R136Q 2D AIThe SynGAP1 R136Q variant is listed in ClinVar as benign and is present in gnomAD (6‑33432704‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑vs‑2 split, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no reported result for this variant. Based on the available predictions, the variant is most likely benign, which aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.433034	Structured	0.657394	Binding	0.351	0.894	0.250					Benign		1	6-33432704-G-A	13	9.17e-6	-11.146	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-2.26	Neutral	0.957	Probably Damaging	0.342	Benign	3.52	Benign	0.01	Affected	3.61	5	0.3171	0.2460		1	1	1.0	-28.06
c.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	-2.12	Neutral	0.018	Benign	0.025	Benign	3.94	Benign	0.03	Affected			0.2012	0.3351		1	1	-0.4	0.04
c.466T>G	F156V 2D AIThe SynGAP1 missense variant F156V is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic status. Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect for F156V, and this conclusion does not conflict with the current ClinVar annotation, which is absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-11.945	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.246	Likely Benign	-2.91	Deleterious	0.981	Probably Damaging	0.954	Probably Damaging	4.03	Benign	0.00	Affected			0.2177	0.2166		-1	-1	1.4	-48.04
c.470G>T	R157L 2D AIThe SynGAP1 missense variant R157L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-8.978	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-3.13	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.81	Benign	0.00	Affected			0.2015	0.3709		-3	-2	8.3	-43.03
c.640C>G	L214V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L214V 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The remaining methods—FoldX, Rosetta, premPS, and AlphaMissense‑Optimized—yield uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of available predictions lean toward pathogenicity, 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	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-9.913	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	1.80	Ambiguous	0.4	0.54	Ambiguous	1.17	Ambiguous	0.89	Ambiguous	0.495	Likely Benign	-2.54	Deleterious	0.384	Benign	0.070	Benign	5.78	Benign	0.01	Affected			0.1469	0.3887		2	1	0.4	-14.03
c.767A>G	N256S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256S is listed in ClinVar as Pathogenic (ClinVar ID 2584352.0) and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, while pathogenic calls come from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy subset gives 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 predictions support a pathogenic effect, aligning with the ClinVar classification. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250					Likely Pathogenic		1				-10.640	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.31	Likely Benign	0.2	0.36	Likely Benign	0.34	Likely Benign	0.48	Likely Benign	0.707	Likely Pathogenic	-4.33	Deleterious	0.997	Probably Damaging	0.970	Probably Damaging	5.87	Benign	0.02	Affected	3.39	15	0.3024	0.5864		1	1	2.7	-27.03
c.989A>G	D330G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D330G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, whereas the majority of algorithms predict a pathogenic impact: FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two predictors (AlphaMissense‑Optimized and premPS) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, classifies the variant as pathogenic. Overall, the preponderance of evidence indicates that D330G is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250											-13.064	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	2.69	Destabilizing	0.2	2.17	Destabilizing	2.43	Destabilizing	0.63	Ambiguous	0.373	Likely Benign	-5.03	Deleterious	0.980	Probably Damaging	0.782	Possibly Damaging	0.94	Pathogenic	0.01	Affected			0.3935	0.5015		1	-1	3.1	-58.04
c.989A>T	D330V 2D 3DClick to see structure in 3D Viewer AISynGAP1 D330V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and premPS, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, and AlphaMissense‑Default. Uncertain predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy assessments show that the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized and Foldetta provide inconclusive results and are therefore not considered evidence. Overall, the preponderance of evidence points to a pathogenic effect for D330V, and 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	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250											-13.176	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	2.06	Destabilizing	0.5	0.57	Ambiguous	1.32	Ambiguous	0.45	Likely Benign	0.428	Likely Benign	-6.40	Deleterious	0.994	Probably Damaging	0.892	Possibly Damaging	0.89	Pathogenic	0.01	Affected			0.0862	0.4633		-2	-3	7.7	-15.96
c.1444C>T	L482F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX and premPS, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as Uncertain, SGM Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for L482F. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.257	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.48	Likely Benign	0.0	1.09	Ambiguous	0.79	Ambiguous	0.43	Likely Benign	0.724	Likely Pathogenic	-3.95	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	-1.22	Pathogenic	0.01	Affected			0.0457	0.1814		2	0	-1.0	34.02
c.1588A>G	K530E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K530E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and polyPhen‑2 HumVar, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus remains Likely Pathogenic, and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K530E. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-14.450	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.2	1.27	Ambiguous	1.03	Ambiguous	0.43	Likely Benign	0.581	Likely Pathogenic	-3.45	Deleterious	0.703	Possibly Damaging	0.276	Benign	-1.57	Pathogenic	0.00	Affected			0.2505	0.0810		0	1	0.4	0.94
c.3116T>A	I1039N 2D AIThe SynGAP1 missense variant I1039N has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status (none is present). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.979204	Binding	0.292	0.806	0.625											-3.469	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.155	Likely Benign	-1.24	Neutral	0.011	Benign	0.010	Benign	2.67	Benign	0.02	Affected			0.1151	0.1311		-2	-3	-8.0	0.94
c.3756G>C	Q1252H 2D AIThe SynGAP1 missense variant Q1252H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-6.891	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-4.02	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1038	0.2149		3	0	0.3	9.01
c.3756G>T	Q1252H 2D AIThe SynGAP1 missense variant Q1252H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the preponderance of evidence from multiple in‑silico predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-6.891	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.175	Likely Benign	-4.02	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.1038	0.2149		3	0	0.3	9.01
c.3794G>A	R1265K 2D AIThe SynGAP1 missense variant R1265K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-5.223	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.344	Likely Benign	-2.49	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.4829	0.3632		3	2	0.6	-28.01
c.3986T>C	L1329P 2D AIThe SynGAP1 missense variant L1329P is listed in gnomAD (ID 6‑33451860‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie and is therefore inconclusive. No Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors (five pathogenic vs three benign) lean toward a pathogenic effect. Because ClinVar contains no classification, there is no conflict with existing clinical annotation. Thus, based on current in silico evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451860-T-C			-2.903	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.165	Likely Benign	-3.74	Deleterious	0.994	Probably Damaging	0.993	Probably Damaging	3.04	Benign	0.00	Affected	3.77	5	0.3396	0.1794		-3	-3	-5.4	-16.04
c.648G>C	Q216H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas those that predict a pathogenic impact are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.532	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	0.638	Likely Pathogenic	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			0.1909	0.4660		3	0	0.3	9.01
c.648G>T	Q216H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q216H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.206376	Structured	0.396100	Uncertain	0.804	0.274	0.000											-10.532	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.0	0.30	Likely Benign	0.30	Likely Benign	0.50	Likely Benign	0.638	Likely Pathogenic	-3.84	Deleterious	0.989	Probably Damaging	0.809	Possibly Damaging	5.85	Benign	0.01	Affected			0.1909	0.4660		3	0	0.3	9.01
c.719A>G	D240G 2D AIThe SynGAP1 missense variant D240G is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Benign predictions are provided by premPS and FATHMM, whereas pathogenic predictions are made by REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. FoldX‑MD is inconclusive, and AlphaMissense‑Optimized is uncertain. High‑accuracy methods show that AlphaMissense‑Optimized is inconclusive, SGM Consensus predicts pathogenic, and Foldetta predicts pathogenic. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the ClinVar uncertain status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000					Uncertain		1				-12.825	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	1.85	Ambiguous	0.1	2.72	Destabilizing	2.29	Destabilizing	0.24	Likely Benign	0.912	Likely Pathogenic	-6.19	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	5.79	Benign	0.01	Affected			0.3474	0.4989		1	-1	3.1	-58.04
c.1088A>C	Y363S 2D AIThe SynGAP1 missense variant Y363S 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, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized is classified as “Uncertain”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the overwhelming majority of evidence points to a pathogenic effect for Y363S, 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	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-11.578	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	3.09	Destabilizing	0.6	3.92	Destabilizing	3.51	Destabilizing	1.45	Destabilizing	0.420	Likely Benign	-8.04	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	1.56	Pathogenic	0.01	Affected			0.5750	0.4208	Weaken	-3	-2	0.5	-76.10
c.1245G>C	E415D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Predictions that are inconclusive or uncertain are FoldX, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, while Foldetta predicts a benign effect. Overall, the balance of evidence leans toward 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.		GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-7.766	In-Between	0.952	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.1	0.21	Likely Benign	0.48	Likely Benign	0.49	Likely Benign	0.220	Likely Benign	-2.60	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.22	Benign	0.04	Affected			0.1777	0.2075		3	2	0.0	-14.03
c.1245G>T	E415D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are FoldX, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta indicates a benign effect. Overall, the majority of standard tools lean toward pathogenicity, and the high‑accuracy consensus also supports a pathogenic classification. Therefore, 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.		GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-7.766	In-Between	0.952	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.1	0.21	Likely Benign	0.48	Likely Benign	0.49	Likely Benign	0.220	Likely Benign	-2.60	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.22	Benign	0.04	Affected			0.1777	0.2075		3	2	0.0	-14.03
c.1265A>C	E422A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422A missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the balance of evidence (seven pathogenic versus six benign predictions) points to a likely pathogenic effect for E422A, and this conclusion is not contradicted by the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-12.088	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.49	Likely Benign	0.0	0.25	Likely Benign	0.37	Likely Benign	0.26	Likely Benign	0.371	Likely Benign	-5.43	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.31	Benign	0.01	Affected			0.2949	0.4459		0	-1	5.3	-58.04
c.1265A>G	E422G 2D 3DClick to see structure in 3D Viewer AISynGAP1 E422G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, premPS, and FATHMM, while pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are provided by FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy analyses indicate that the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a likely pathogenic effect, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta shows no definitive stability change. Overall, the majority of evidence points toward a pathogenic impact for E422G, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-11.468	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	1.13	Ambiguous	0.0	1.25	Ambiguous	1.19	Ambiguous	0.39	Likely Benign	0.488	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.01	Affected			0.2440	0.4184		0	-2	3.1	-72.06
c.1306G>C	E436Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436Q is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include premPS and FATHMM, while the majority of tools predict a pathogenic outcome: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the consensus of pathogenic predictions outweighs benign ones, and the high‑accuracy tools reinforce a pathogenic classification. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.413	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	1.58	Ambiguous	1.05	Ambiguous	0.50	Likely Benign	0.607	Likely Pathogenic	-2.76	Deleterious	0.992	Probably Damaging	0.946	Probably Damaging	4.64	Benign	0.01	Affected			0.1237	0.5809		2	2	0.0	-0.98
c.1469C>T	A490V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A490V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly favor a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. No tool predicts a benign outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus remains likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Overall, the consensus of the majority of algorithms points to a pathogenic effect, and this conclusion does not conflict with the absence of ClinVar annotation. Thus, the variant is most likely pathogenic, with no contradiction from ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.322979	Uncertain	0.938	0.210	0.125											-10.348	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.73	Ambiguous	0.3	0.62	Ambiguous	0.68	Ambiguous	0.69	Ambiguous	0.817	Likely Pathogenic	-3.93	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.26	Pathogenic	0.04	Affected			0.0983	0.4213		0	0	2.4	28.05
c.1478C>T	A493V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A493V missense variant has no ClinVar entry and is reported in gnomAD (6‑33438510‑C‑T). Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Benign predictions are limited to SIFT and Foldetta. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus indicates likely pathogenic, and Foldetta predicts benign stability. No other tools provide conclusive evidence. Overall, the preponderance of pathogenic predictions, including the consensus and multiple independent algorithms, suggests 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	0.102787	Structured	0.340081	Uncertain	0.966	0.182	0.000								6-33438510-C-T	3	1.86e-6	-12.511	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.1	-0.67	Ambiguous	-0.06	Likely Benign	0.91	Ambiguous	0.735	Likely Pathogenic	-3.84	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.31	Pathogenic	0.10	Tolerated	3.37	35	0.0877	0.3860		0	0	2.4	28.05
c.1583C>G	P528R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P528R missense variant is not reported in ClinVar and is absent from gnomAD. No in silico predictor classifies it as benign; the following tools predict pathogenicity: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions that are uncertain or inconclusive (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-16.367	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.76	Ambiguous	0.4	0.67	Ambiguous	0.72	Ambiguous	0.73	Ambiguous	0.615	Likely Pathogenic	-8.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.49	Pathogenic	0.01	Affected			0.1261	0.2543		0	-2	-2.9	59.07
c.1876A>T	I626F 2D 3DClick to see structure in 3D Viewer AISynGAP1 I626F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM‑Consensus (derived from a majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Taken together, the overwhelming majority of evidence indicates that I626F 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	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-14.483	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	4.37	Destabilizing	0.3	2.12	Destabilizing	3.25	Destabilizing	0.66	Ambiguous	0.631	Likely Pathogenic	-3.78	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.07	Benign	0.00	Affected			0.0481	0.1964		1	0	-1.7	34.02
c.1889T>G	I630S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I630S is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tool predicts a benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as pathogenic. No contradictory evidence is present. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not conflict with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.036106	Uncertain	0.966	0.236	0.000											-12.527	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	3.61	Destabilizing	0.1	3.74	Destabilizing	3.68	Destabilizing	2.25	Destabilizing	0.851	Likely Pathogenic	-3.86	Deleterious	1.000	Probably Damaging	0.981	Probably Damaging	-1.44	Pathogenic	0.00	Affected			0.2363	0.0858		-1	-2	-5.3	-26.08
c.2465C>G	T822R 2D AIThe SynGAP1 missense variant T822R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie and therefore unavailable; Foldetta predictions are not provided. Overall, the balance of evidence (five pathogenic versus three benign predictions) suggests 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.			0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											0.414	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.237	Likely Benign	-2.74	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	2.50	Benign	0.05	Affected			0.1182	0.3439		-1	-1	-3.8	55.08
c.2944T>G	Y982D 2D AIThe SynGAP1 missense variant Y982D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-5.021	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-1.29	Neutral	0.990	Probably Damaging	0.856	Possibly Damaging	3.87	Benign	0.00	Affected			0.3959	0.0545		-4	-3	-2.2	-48.09
c.3787A>T	I1263F 2D AIThe SynGAP1 missense variant I1263F is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Because the majority of evidence points to a deleterious effect and there is no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-5.887	Likely Benign	0.952	Likely Pathogenic	Ambiguous										0.335	Likely Benign	-3.32	Deleterious	0.968	Probably Damaging	0.637	Possibly Damaging	1.81	Pathogenic	0.00	Affected			0.0494	0.2375		1	0	-1.7	34.02
c.440A>G	Q147R 2D AIThe SynGAP1 missense variant Q147R is not 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, and FATHMM. Tools that agree on 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‑to‑2 split, and Foldetta results are unavailable. Overall, more tools predict a benign outcome (five vs. three pathogenic predictions, with one uncertain). Therefore, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-12.301	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.166	Likely Benign	-2.22	Neutral	0.079	Benign	0.052	Benign	3.91	Benign	0.02	Affected			0.1760	0.1042		1	1	-1.0	28.06
c.535G>C	E179Q 2D AIThe SynGAP1 missense variant E179Q has no ClinVar record (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Computational predictions are split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy consensus tools are inconclusive: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a tie, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic based on current predictions, and there is no ClinVar status to contradict this ambiguous assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-10.388	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-1.82	Neutral	0.818	Possibly Damaging	0.419	Benign	3.99	Benign	0.02	Affected			0.1674	0.7383		2	2	0.0	-0.98
c.563G>A	S188N 2D AIThe SynGAP1 missense variant S188N is not 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 (five benign vs three pathogenic) suggest a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.307	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous										0.095	Likely Benign	-2.34	Neutral	0.259	Benign	0.048	Benign	3.92	Benign	0.01	Affected			0.1420	0.5658		1	1	-2.7	27.03
c.793A>G	K265E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265E missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and Foldetta. Those that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, FoldX, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a 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 evaluated tools (eight pathogenic vs. three benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-12.163	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.63	Ambiguous	0.2	0.00	Likely Benign	0.32	Likely Benign	0.95	Ambiguous	0.461	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.94	Pathogenic	0.05	Affected			0.3801	0.0882		0	1	0.4	0.94
c.1010A>C	K337T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, FoldX, and premPS, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools report uncertainty: Rosetta, Foldetta, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Pathogenic. In the high‑accuracy subset, AlphaMissense‑Optimized remains uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta is uncertain. Taken together, the majority of evidence points toward a deleterious effect. Therefore, K337T is most likely pathogenic, 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	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-10.896	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.45	Likely Benign	0.2	1.33	Ambiguous	0.89	Ambiguous	0.25	Likely Benign	0.338	Likely Benign	-5.32	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.70	Pathogenic	0.01	Affected			0.1741	0.3354		0	-1	3.2	-27.07
c.1336G>A	E446K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E446K is not reported in ClinVar (ClinVar status: not present) and is found in gnomAD (ID 6‑33438241‑G‑A). Prediction tools that agree on a benign effect include only FATHMM. Tools that agree on a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy methods give the following: AlphaMissense‑Optimized is uncertain; SGM‑Consensus indicates likely pathogenic; Foldetta is uncertain. Overall, the majority of evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.276479	Uncertain	0.940	0.216	0.000								6-33438241-G-A	1	6.19e-7	-14.140	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.80	Ambiguous	0.4	1.57	Ambiguous	1.19	Ambiguous	0.81	Ambiguous	0.518	Likely Pathogenic	-3.75	Deleterious	0.994	Probably Damaging	0.975	Probably Damaging	3.36	Benign	0.01	Affected	3.38	31	0.2141	0.6511		1	0	-0.4	-0.94
c.1456G>C	E486Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and AlphaMissense‑Optimized as uncertain. No prediction or stability result is missing or inconclusive beyond the stated uncertainty. Overall, the evidence is balanced, with an equal number of benign and pathogenic calls, and the high‑accuracy tools provide opposing conclusions. Thus, the variant is most likely benign based on the preponderance of benign predictions, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-10.549	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.12	Likely Benign	0.1	0.00	Likely Benign	0.06	Likely Benign	0.24	Likely Benign	0.334	Likely Benign	-2.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.38	Benign	0.09	Tolerated			0.0888	0.5880		2	2	0.0	-0.98
c.1589A>T	K530M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530M 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 premPS. Tools that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Based on the predominance of pathogenic predictions and the SGM Consensus result, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.235	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.0	1.26	Ambiguous	0.89	Ambiguous	0.24	Likely Benign	0.671	Likely Pathogenic	-5.17	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.69	Pathogenic	0.00	Affected			0.0745	0.3123		0	-1	5.8	3.02
c.1748A>G	D583G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D583G missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and ESM1b, whereas the majority of algorithms—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—classify it as pathogenic. Uncertain results come from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessment shows the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and AlphaMissense‑Optimized remains inconclusive; Foldetta also reports no definitive stability change. Overall, the preponderance of evidence points to a pathogenic effect for D583G, and this conclusion does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-6.765	Likely Benign	0.953	Likely Pathogenic	Ambiguous	1.10	Ambiguous	0.2	0.56	Ambiguous	0.83	Ambiguous	0.10	Likely Benign	0.850	Likely Pathogenic	-6.77	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.43	Pathogenic	0.03	Affected			0.3072	0.4284		1	-1	3.1	-58.04
c.1891C>A	Q631K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q631K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Foldetta, and FATHMM, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. Uncertain or inconclusive results are reported by Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect; the SGM‑Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome; AlphaMissense‑Optimized remains uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.038963	Uncertain	0.948	0.230	0.000											-15.194	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	-0.37	Likely Benign	0.1	1.13	Ambiguous	0.38	Likely Benign	0.88	Ambiguous	0.596	Likely Pathogenic	-3.98	Deleterious	0.958	Probably Damaging	0.931	Probably Damaging	2.79	Benign	0.01	Affected			0.1288	0.2157		1	1	-0.4	0.04
c.195C>A	H65Q 2D AIThe SynGAP1 missense variant H65Q is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33425803‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, 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. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.476188	Uncertain	0.458	0.758	0.125								6-33425803-C-A	1	6.20e-7	-2.966	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.035	Likely Benign	-1.46	Neutral	0.462	Possibly Damaging	0.227	Benign	4.19	Benign	0.00	Affected	4.32	1	0.1059	0.2900		0	3	-0.3	-9.01
c.195C>G	H65Q 2D AIThe SynGAP1 H65Q missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those 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 benign, while AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for H65Q. 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											-2.966	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.035	Likely Benign	-1.46	Neutral	0.462	Possibly Damaging	0.227	Benign	4.19	Benign	0.00	Affected	4.32	1	0.1059	0.2900		0	3	-0.3	-9.01
c.2042G>T	G681V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus predicts a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic outcome. No other high‑confidence predictions are available. Taken together, the consensus of pathogenic predictions outweighs the single benign call, indicating that G681V is most likely pathogenic. This assessment is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-14.043	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	3.21	Destabilizing	2.0	6.12	Destabilizing	4.67	Destabilizing	0.64	Ambiguous	0.572	Likely Pathogenic	-8.98	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	3.33	Benign	0.01	Affected			0.1350	0.3840		-1	-3	4.6	42.08
c.2059C>G	R687G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R687G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools (SGM‑Consensus, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta indicates a destabilizing, pathogenic effect. AlphaMissense‑Optimized is uncertain and therefore treated as unavailable. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000											-12.900	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	2.94	Destabilizing	0.3	2.53	Destabilizing	2.74	Destabilizing	1.27	Destabilizing	0.360	Likely Benign	-6.26	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.88	Benign	0.01	Affected			0.2508	0.2119		-3	-2	4.1	-99.14
c.2941G>C	G981R 2D AIThe SynGAP1 missense variant G981R is not 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, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely benign based on current predictive tools. 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											-1.264	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.207	Likely Benign	-2.11	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	3.74	Benign	0.00	Affected			0.0990	0.4776		-3	-2	-4.1	99.14
c.3216G>C	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3216G>T	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3538C>T	L1180F 2D AIThe SynGAP1 missense variant L1180F is not 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 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of high‑accuracy predictions lean toward a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-5.370	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.077	Likely Benign	-1.29	Neutral	0.749	Possibly Damaging	0.444	Benign	2.65	Benign	0.00	Affected			0.0516	0.2345		2	0	-1.0	34.02
c.3596A>C	E1199A 2D AIThe SynGAP1 missense variant E1199A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy consensus, SGM‑Consensus, also indicates a likely pathogenic outcome, while AlphaMissense‑Optimized is uncertain and Foldetta results are unavailable. Taken together, the majority of evidence points to a pathogenic effect for E1199A, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-13.556	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.367	Likely Benign	-4.32	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.48	Pathogenic	0.00	Affected			0.2858	0.3834		0	-1	5.3	-58.04
c.3604A>C	I1202L 2D AIThe SynGAP1 I1202L missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and SIFT, whereas those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-8.026	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.119	Likely Benign	-1.27	Neutral	0.981	Probably Damaging	0.970	Probably Damaging	1.94	Pathogenic	0.59	Tolerated			0.0788	0.2874		2	2	-0.7	0.00
c.3625C>G	L1209V 2D AIThe SynGAP1 L1209V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Taken together, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-9.962	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.152	Likely Benign	-2.39	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1383	0.2289		2	1	0.4	-14.03
c.862G>C	D288H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D288H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, and premPS. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling the variant as Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect on protein folding stability. Overall, the majority of tools (7/12) predict pathogenicity, and the high‑accuracy consensus leans toward pathogenic, with no conflict with ClinVar status. 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	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-12.589	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.1	0.36	Likely Benign	0.22	Likely Benign	-0.02	Likely Benign	0.460	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.1639	0.6254		1	-1	0.3	22.05
c.1777C>T	L593F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L593F is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive—FoldX, Foldetta, premPS, and AlphaMissense‑Optimized—are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-12.723	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	1.46	Ambiguous	0.4	0.24	Likely Benign	0.85	Ambiguous	0.62	Ambiguous	0.304	Likely Benign	-3.78	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.95	Benign	0.01	Affected			0.0884	0.2631		2	0	-1.0	34.02
c.1795T>A	C599S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, which scores the variant as benign. All other evaluated algorithms—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta (combining FoldX‑MD and Rosetta) as Uncertain. No prediction or folding stability result is missing; all available data are reported. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.336	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.57	Ambiguous	1.21	Ambiguous	1.27	Destabilizing	0.919	Likely Pathogenic	-9.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.45	Pathogenic	0.06	Tolerated			0.3414	0.1415		0	-1	-3.3	-16.06
c.1796G>C	C599S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599S is not reported in ClinVar and has no entries in gnomAD. Prediction tools cluster into two groups: the sole benign prediction comes from SIFT, whereas the remaining nine tools—REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—indicate pathogenicity. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is uncertain, SGM‑Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. FoldX and Rosetta individually report uncertain stability changes. Overall, the majority of evidence points to a deleterious effect, so the variant is most likely pathogenic, with no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000											-13.336	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	0.85	Ambiguous	0.0	1.57	Ambiguous	1.21	Ambiguous	1.27	Destabilizing	0.866	Likely Pathogenic	-9.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.45	Pathogenic	0.06	Tolerated			0.3414	0.1415		0	-1	-3.3	-16.06
c.196C>A	P66T 2D AIThe SynGAP1 missense variant P66T is not 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 classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the balance of evidence leans toward a benign impact, with one high‑accuracy tool (SGM‑Consensus) supporting this view and no ClinVar entry to contradict it. Thus, the variant is most likely benign. 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											-3.373	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.139	Likely Benign	-1.81	Neutral	0.909	Possibly Damaging	0.641	Possibly Damaging	4.00	Benign	0.00	Affected			0.1747	0.5866		0	-1	0.9	3.99
c.2780T>A	F927Y 2D AIThe SynGAP1 missense variant F927Y is not 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 tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.529623	Disordered	0.985043	Binding	0.324	0.854	0.250											-5.244	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-2.29	Neutral	0.997	Probably Damaging	0.987	Probably Damaging	1.40	Pathogenic	0.00	Affected			0.1551	0.1518		7	3	-4.1	16.00
c.2792T>A	L931H 2D AIThe SynGAP1 missense variant L931H has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. ESM1b and AlphaMissense‑Optimized are uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-7.495	In-Between	0.954	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-3.76	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.1198	0.1205		-2	-3	-7.0	23.98
c.3008G>T	S1003I 2D AIThe SynGAP1 missense variant S1003I is not 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. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign votes); and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Based on the overall distribution of predictions, the variant is most likely pathogenic. 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.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625											-8.952	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.189	Likely Benign	-2.31	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.50	Benign	0.00	Affected			0.1294	0.5735		-1	-2	5.3	26.08
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	-2.26	Neutral	1.000	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected	3.77	5	0.1871	0.4072		0	1	-0.4	-0.94
c.3678G>C	Q1226H 2D AIThe SynGAP1 missense variant Q1226H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists for Q1226H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-8.363	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0913	0.3230		3	0	0.3	9.01
c.3678G>T	Q1226H 2D AIThe SynGAP1 missense variant Q1226H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists for Q1226H. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-8.363	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.241	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0913	0.3230		3	0	0.3	9.01
c.3806T>C	V1269A 2D AIThe SynGAP1 missense variant V1269A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a larger group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and no Foldetta data. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-6.115	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.291	Likely Benign	-3.38	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.2699	0.2312		0	0	-2.4	-28.05
c.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	-3.43	Deleterious	0.931	Possibly Damaging	0.410	Benign	3.75	Benign	0.01	Affected			0.2065	0.5095		0	-2	2.9	-59.07
c.559C>A	L187M 2D AIThe SynGAP1 missense variant L187M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, which would assess protein‑folding stability, has no available output for this variant. Overall, the majority of predictions (five pathogenic vs. three benign) lean toward pathogenicity, 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.			0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-8.814	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.136	Likely Benign	-1.35	Neutral	0.971	Probably Damaging	0.641	Possibly Damaging	3.72	Benign	0.02	Affected			0.0848	0.3613		4	2	-1.9	18.03
c.569G>T	S190I 2D AIThe SynGAP1 missense variant S190I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The 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. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points to a pathogenic impact, 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		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250											-9.868	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous										0.316	Likely Benign	-3.39	Deleterious	0.845	Possibly Damaging	0.368	Benign	4.03	Benign	0.03	Affected			0.0769	0.5963		-1	-2	5.3	26.08
c.880A>T	T294S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T294S missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). In silico predictors that classify the variant as benign are absent; all available tools that provide a definitive call predict a deleterious effect. Pathogenic predictions come from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results are reported for FoldX, Rosetta, Foldetta, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of pathogenic calls and the SGM Consensus support a pathogenic classification. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no opposing evidence. 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											-7.785	In-Between	0.954	Likely Pathogenic	Ambiguous	1.12	Ambiguous	0.2	1.70	Ambiguous	1.41	Ambiguous	1.19	Destabilizing	0.613	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	0.08	Pathogenic	0.03	Affected			0.2983	0.3396		1	1	-0.1	-14.03
c.881C>G	T294S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T294S missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). In silico predictors that classify the variant as benign are absent; all available tools that provide a definitive call predict a deleterious effect. Pathogenic predictions come from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Uncertain or inconclusive results are reported for FoldX, Rosetta, Foldetta, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of pathogenic calls and the SGM Consensus support a pathogenic classification. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no opposing evidence. 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											-7.785	In-Between	0.954	Likely Pathogenic	Ambiguous	1.12	Ambiguous	0.2	1.70	Ambiguous	1.41	Ambiguous	1.19	Destabilizing	0.583	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	0.08	Pathogenic	0.03	Affected			0.2983	0.3396		1	1	-0.1	-14.03
c.1529T>G	I510S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I510S is listed in ClinVar as Pathogenic (ClinVar ID 449946.0) and is not reported in gnomAD. Prediction tools that assess the variant’s effect all converge on a deleterious outcome: 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) all indicate pathogenicity. No tool predicts a benign effect. High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250630	Uncertain	0.945	0.273	0.000					Likely Pathogenic		1				-11.661	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous	4.00	Destabilizing	0.1	3.78	Destabilizing	3.89	Destabilizing	2.34	Destabilizing	0.926	Likely Pathogenic	-4.63	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.44	Pathogenic	0.00	Affected	3.37	35	0.2395	0.0858		-1	-2	-5.3	-26.08	201.4	45.9	-0.4	0.2	0.0	0.3							X	Potentially Pathogenic	Ile510 is located in the middle of an α-helix (res. Gly502-Tyr518) within the inter-helix space of three helices (res. Gly502-Tyr518, Ala533-Val560, and res. Glu582-Met603). In the WT simulations, the sec-butyl side chain of Ile510 hydrophobically packs with other residues in the inter-helix space (e.g., Leu506, Leu610, Ile514, Ile602, Leu598). In the variant simulations, the hydroxyl group of Ser510 forms a hydrogen bond with the backbone atoms of Leu506 and Gly511 in the same α-helix, which could further weaken the α-helix integrity. This α-helix already shows weakness in the WT simulations due to Gly511. Although the simulations do not show large-scale effects, the residue swap could have a substantial impact due to the fundamental role of hydrophobic packing during protein folding.
c.2952G>C	K984N 2D AIThe SynGAP1 missense variant K984N is catalogued in gnomAD (6‑33443504‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign,” and Foldetta (which integrates FoldX‑MD and Rosetta outputs) has no available result for this residue. Overall, the balance of evidence leans toward a benign effect, with no pathogenic ClinVar classification to contradict this inference. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750								6-33443504-G-C	1	6.20e-7	-3.020	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.091	Likely Benign	0.52	Neutral	0.951	Possibly Damaging	0.637	Possibly Damaging	2.89	Benign	0.00	Affected	4.32	1	0.4138	0.1677		0	1	0.4	-14.07
c.2952G>T	K984N 2D AISynGAP1 missense variant K984N has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is Uncertain, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750											-3.020	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.091	Likely Benign	0.52	Neutral	0.951	Possibly Damaging	0.637	Possibly Damaging	2.89	Benign	0.00	Affected	4.32	1	0.4138	0.1677		0	1	0.4	-14.07
c.3235A>C	S1079R 2D AIThe SynGAP1 missense variant S1079R 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, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. The SGM‑Consensus, which aggregates 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 (a protein‑folding stability method combining FoldX‑MD and Rosetta) 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 is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750											-4.579	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.163	Likely Benign	-1.81	Neutral	0.177	Benign	0.075	Benign	3.86	Benign	0.00	Affected	3.77	5	0.0811	0.4028		0	-1	-3.7	69.11
c.3237C>A	S1079R 2D AIThe SynGAP1 missense variant S1079R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (gnomAD ID 6‑33443789‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is inconclusive. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments are limited: AlphaMissense‑Optimized remains uncertain, SGM‑Consensus is benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750					Uncertain		1	6-33443789-C-A	4	2.51e-6	-4.579	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-1.81	Neutral	0.177	Benign	0.075	Benign	3.86	Benign	0.00	Affected	3.77	5	0.0811	0.4028		0	-1	-3.7	69.11
c.3237C>G	S1079R 2D AIThe SynGAP1 missense variant S1079R is listed in ClinVar (ID 1047537.0) 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, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta (FoldX‑MD/Rosetta stability) result is available. High‑accuracy assessments therefore show a benign consensus (SGM‑Consensus) with one uncertain AlphaMissense‑Optimized prediction and no destabilizing Foldetta evidence. Overall, the majority of predictions support a benign classification, which is consistent with the ClinVar status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750					Benign		1				-4.579	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-1.81	Neutral	0.177	Benign	0.075	Benign	3.86	Benign	0.00	Affected	3.77	5	0.0811	0.4028		0	-1	-3.7	69.11
c.3775A>T	I1259F 2D AIThe SynGAP1 missense variant I1259F 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, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized returns an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta data are unavailable. Overall, the majority of evidence (five pathogenic vs. three benign) points toward a pathogenic 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.		Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250											-10.666	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.301	Likely Benign	-1.68	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.55	Benign	0.03	Affected			0.0428	0.2563		1	0	-1.7	34.02
c.3821G>C	R1274P 2D AIThe SynGAP1 missense variant R1274P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that R1274P is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.613573	Disordered	0.779985	Binding	0.746	0.688	0.625											-6.145	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.179	Likely Benign	-4.02	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.48	Pathogenic	0.01	Affected			0.2166	0.3095		0	-2	2.9	-59.07
c.433A>C	K145Q 2D AIThe SynGAP1 missense variant K145Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Computational predictions are split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy tools give no definitive verdict: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic according to current predictions, and there is no ClinVar annotation to contradict this ambiguous computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-9.676	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.163	Likely Benign	-2.34	Neutral	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.4233	0.1478		1	1	0.4	-0.04
c.441A>C	Q147H 2D AIThe SynGAP1 missense variant Q147H is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the balance of evidence, especially the SGM Consensus and the majority of individual predictors, indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-9.759	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.102	Likely Benign	-2.70	Deleterious	0.380	Benign	0.265	Benign	3.87	Benign	0.01	Affected			0.1528	0.3220		3	0	0.3	9.01
c.441A>T	Q147H 2D AIThe SynGAP1 missense variant Q147H is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM, while pathogenic calls arise from PROVEAN, SIFT, ESM1b and AlphaMissense‑Default. Grouping by consensus, four tools predict benign and four predict pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Taken together, the balance of evidence favors a pathogenic interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.503877	Binding	0.349	0.840	0.625											-9.759	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.102	Likely Benign	-2.70	Deleterious	0.380	Benign	0.265	Benign	3.87	Benign	0.01	Affected			0.1528	0.3220		3	0	0.3	9.01
c.536A>C	E179A 2D AISynGAP1 E179A is not reported in ClinVar and has no entry in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is Uncertain, SGM‑Consensus is Likely Pathogenic, and Foldetta data are unavailable. Overall, the majority of individual predictors lean benign, yet the consensus and high‑accuracy tools indicate pathogenicity, leaving the variant’s effect ambiguous. The predictions do not contradict ClinVar status, which has no entry for this variant. Based on the aggregate predictions, the variant is most likely benign, although the SGM‑Consensus and high‑accuracy tools raise a pathogenic signal, making the overall assessment inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.517562	Disordered	0.448169	Uncertain	0.329	0.635	0.500											-9.862	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.124	Likely Benign	-3.61	Deleterious	0.131	Benign	0.079	Benign	4.01	Benign	0.09	Tolerated			0.4465	0.7186		0	-1	5.3	-58.04
c.539C>T	S180L 2D AIThe SynGAP1 missense variant S180L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a “Likely Pathogenic” classification. AlphaMissense‑Optimized is uncertain, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. 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											-12.967	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.250	Likely Benign	-3.80	Deleterious	0.608	Possibly Damaging	0.202	Benign	3.84	Benign	0.00	Affected			0.0885	0.5550		-3	-2	4.6	26.08
c.580G>C	E194Q 2D AIThe SynGAP1 missense variant E194Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, more evidence supports a pathogenic classification (5 pathogenic vs. 3 benign predictions). 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.			0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-8.902	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.140	Likely Benign	-1.97	Neutral	0.849	Possibly Damaging	0.478	Possibly Damaging	4.00	Benign	0.02	Affected			0.1043	0.4954		2	2	0.0	-0.98
c.781G>T	D261Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D261Y missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are premPS and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. No prediction or folding stability result is missing or inconclusive beyond the stated uncertainties. Overall, the preponderance of evidence points to a pathogenic effect for D261Y, and 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	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-14.961	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous	2.93	Destabilizing	2.1	0.81	Ambiguous	1.87	Ambiguous	-0.12	Likely Benign	0.886	Likely Pathogenic	-5.50	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	5.73	Benign	0.01	Affected			0.0474	0.5476		-4	-3	2.2	48.09
c.1082A>C	Q361P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361P is listed in ClinVar as Pathogenic (ClinVar ID 3235087.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect are REVEL and premPS. All other evaluated algorithms—FoldX, Rosetta, Foldetta, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy methods specifically give a pathogenic verdict: AlphaMissense‑Optimized is Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. Based on the overwhelming agreement of these predictions, the variant is most likely pathogenic, which is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250					Likely Pathogenic		1				-13.280	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	3.12	Destabilizing	0.0	3.45	Destabilizing	3.29	Destabilizing	0.38	Likely Benign	0.482	Likely Benign	-3.03	Deleterious	0.996	Probably Damaging	0.979	Probably Damaging	1.63	Pathogenic	0.05	Affected	3.37	25	0.1986	0.5151		-1	0	1.9	-31.01
c.1214G>T	R405L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R405L missense change is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are Rosetta and FATHMM, while the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) indicate a pathogenic or likely pathogenic impact. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labeling it likely pathogenic, and Foldetta providing an inconclusive stability prediction. Overall, the preponderance of evidence points to a pathogenic effect for R405L, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.576	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.43	Ambiguous	0.7	0.40	Likely Benign	0.92	Ambiguous	0.72	Ambiguous	0.512	Likely Pathogenic	-6.35	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.64	Benign	0.01	Affected			0.2126	0.5555		-3	-2	8.3	-43.03
c.1256A>G	E419G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E419G is listed in ClinVar with an uncertain significance (ClinVar ID 2004834.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms likely pathogenic, and the Foldetta stability analysis is inconclusive. No evidence from FoldX, Rosetta, or premPS is available. Overall, the preponderance of predictions indicates that E419G is most likely pathogenic, which contrasts with the current ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000					Uncertain		1				-10.589	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.41	Ambiguous	0.0	1.94	Ambiguous	1.68	Ambiguous	0.83	Ambiguous	0.469	Likely Benign	-6.42	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.31	Benign	0.02	Affected	3.37	29	0.2992	0.5728		0	-2	3.1	-72.06	165.3	110.8	0.0	0.0	-0.1	0.0		X						Potentially Pathogenic	The carboxylate group of Glu419, located on an α helix (res. Met414-Glu436), forms a salt bridge with the side chain of either Arg716 or Lys418 from an opposing helix (res. Pro713-Arg726). The backbone amide group of Glu419 does not form H-bonds, resulting in a slight bend in the α helix. Thus, although glycine is known as an “α helix breaker,” the residue swap does not disrupt the continuity or integrity of the α helix. However, because Gly419 cannot form a salt bridge with the guanidinium group of the Arg716 side chain, the C2-GAP domain tertiary structure could be compromised during folding.
c.142T>C	F48L 2D AIThe SynGAP1 missense variant F48L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence and no Foldetta data is available. Thus, the variant is most likely benign based on the consensus of available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-4.955	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.108	Likely Benign	-1.56	Neutral	0.022	Benign	0.016	Benign	4.16	Benign	0.00	Affected			0.2641	0.3082		2	0	1.0	-34.02
c.144C>A	F48L 2D AIThe SynGAP1 missense variant F48L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence and no Foldetta data is available. Thus, the variant is most likely benign based on the consensus of available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-4.955	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.052	Likely Benign	-1.56	Neutral	0.022	Benign	0.016	Benign	4.16	Benign	0.00	Affected			0.2641	0.3082		2	0	1.0	-34.02
c.144C>G	F48L 2D AIThe SynGAP1 missense variant F48L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence and no Foldetta data is available. Thus, the variant is most likely benign based on the consensus of available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-4.955	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.053	Likely Benign	-1.56	Neutral	0.022	Benign	0.016	Benign	4.16	Benign	0.00	Affected			0.2641	0.3082		2	0	1.0	-34.02
c.1739G>C	G580A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580A is not reported in ClinVar (ClinVar status: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity are unanimous: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus all predict a deleterious effect. Tools with uncertain or inconclusive results (Rosetta and premPS) are noted as unavailable for pathogenicity inference. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta, a protein‑folding stability predictor that integrates FoldX‑MD and Rosetta outputs, also classifies the variant as Pathogenic. Consequently, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-10.841	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	2.84	Destabilizing	0.1	1.55	Ambiguous	2.20	Destabilizing	0.64	Ambiguous	0.646	Likely Pathogenic	-5.73	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.22	Pathogenic	0.05	Affected			0.3657	0.2862		1	0	2.2	14.03
c.1829T>G	L610R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610R 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. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic outcome; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-13.855	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	5.14	Destabilizing	0.5	4.60	Destabilizing	4.87	Destabilizing	1.89	Destabilizing	0.949	Likely Pathogenic	-5.94	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.58	Pathogenic	0.00	Affected			0.1334	0.0615		-3	-2	-8.3	43.03
c.1836G>C	Q612H 2D AIThe SynGAP1 missense variant Q612H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to Rosetta, which scores the variant as benign. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. FoldX and premPS are inconclusive, and Foldetta is unavailable for definitive interpretation. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000											-9.733	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.70	Ambiguous	0.9	0.39	Likely Benign	0.55	Ambiguous	0.79	Ambiguous	0.550	Likely Pathogenic	-4.55	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	-1.26	Pathogenic	0.02	Affected			0.1379	0.3084		3	0	0.3	9.01
c.1836G>T	Q612H 2D AIThe SynGAP1 missense variant Q612H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to Rosetta, which scores the variant as benign. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. FoldX and premPS are inconclusive, and Foldetta is unavailable for definitive interpretation. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000											-9.733	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.70	Ambiguous	0.9	0.39	Likely Benign	0.55	Ambiguous	0.79	Ambiguous	0.550	Likely Pathogenic	-4.55	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	-1.26	Pathogenic	0.02	Affected			0.1379	0.3084		3	0	0.3	9.01
c.203T>C	L68P 2D AIThe SynGAP1 missense variant L68P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward pathogenic, but the consensus from SGM and the high‑accuracy AlphaMissense‑Optimized are contradictory, leaving the variant’s clinical significance uncertain. No conflict exists 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 Benign		0.534167	Disordered	0.470567	Uncertain	0.405	0.768	0.250											-2.122	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.143	Likely Benign	-0.57	Neutral	0.943	Possibly Damaging	0.766	Possibly Damaging	4.09	Benign	0.00	Affected			0.2827	0.1382		-3	-3	-5.4	-16.04
c.2147G>C	R716P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R716P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, premPS, and FATHMM; pathogenic predictions come from AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, Rosetta, Foldetta, and the SGM‑Consensus score. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000											-10.744	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	5.67	Destabilizing	2.93	Destabilizing	0.49	Likely Benign	0.320	Likely Benign	-5.75	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.33	Benign	0.01	Affected			0.2140	0.3576		0	-2	2.9	-59.07
c.3119G>A	G1040D 2D AIThe SynGAP1 missense variant G1040D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The high‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that G1040D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625											-4.154	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.761	Likely Pathogenic	-2.82	Deleterious	0.986	Probably Damaging	0.787	Possibly Damaging	-0.74	Pathogenic	0.00	Affected			0.1677	0.2042		1	-1	-3.1	58.04
c.3463G>C	V1155L 2D AIThe SynGAP1 missense variant V1155L is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in silico predictors shows a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar) and both AlphaMissense models. When predictions are grouped by agreement, the benign set includes five tools and the pathogenic set includes four. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence, especially from the high‑accuracy AlphaMissense‑Optimized and the SGM‑Consensus, suggests the variant is most likely benign, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-2.823	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.229	Likely Benign	-1.26	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.63	Benign	0.09	Tolerated			0.0951	0.4175		2	1	-0.4	14.03
c.3463G>T	V1155L 2D AIThe SynGAP1 missense variant V1155L is not reported in ClinVar and has no gnomAD entry. Consensus from multiple in silico predictors shows a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar) and both AlphaMissense models. When predictions are grouped by agreement, the benign set includes five tools and the pathogenic set includes four. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence, especially from the high‑accuracy AlphaMissense‑Optimized and the SGM‑Consensus, suggests the variant is most likely benign, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-2.823	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.229	Likely Benign	-1.26	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.63	Benign	0.09	Tolerated			0.0951	0.4175		2	1	-0.4	14.03
c.3814G>A	E1272K 2D AIThe SynGAP1 E1272K missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are made by REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-4.227	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.312	Likely Benign	-3.37	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1544	0.5488		0	1	-0.4	-0.94
c.3986T>A	L1329Q 2D AIThe SynGAP1 missense variant L1329Q is reported in gnomAD (ID 6‑33451860‑T‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a deleterious effect, indicating that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451860-T-A			-4.106	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic										0.157	Likely Benign	-3.31	Deleterious	0.994	Probably Damaging	0.993	Probably Damaging	3.05	Benign	0.00	Affected	3.77	5	0.1382	0.1505		-2	-2	-7.3	14.97
c.431C>A	T144K 2D AIThe SynGAP1 T144K variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.666105	Disordered	0.524000	Binding	0.335	0.838	0.625											-15.436	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-2.83	Deleterious	0.180	Benign	0.063	Benign	3.76	Benign	0.00	Affected			0.1462	0.3179		0	-1	-3.2	27.07
c.809A>C	E270A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E270A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools cluster into three groups: benign predictions are made only by premPS; pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; and three tools (FoldX, Rosetta, Foldetta) give uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta remains uncertain. Overall, the majority of evidence points to a deleterious effect. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125											-13.618	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.64	Ambiguous	0.2	0.77	Ambiguous	0.71	Ambiguous	0.41	Likely Benign	0.547	Likely Pathogenic	-5.52	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.4122	0.3951		0	-1	5.3	-58.04
c.952C>T	P318S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318S is present in gnomAD (variant ID 6‑33437857‑C‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a deleterious effect. Pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Taken together, the overwhelming majority of evidence supports a pathogenic classification, and this conclusion is consistent with the absence of a ClinVar record rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000								6-33437857-C-T	1	6.19e-7	-9.954	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	2.22	Destabilizing	0.1	1.71	Ambiguous	1.97	Ambiguous	1.00	Destabilizing	0.626	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.87	Pathogenic	0.03	Affected	3.38	23	0.3692	0.5653		-1	1	0.8	-10.04
c.988G>T	D330Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D330Y 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 premPS, whereas the remaining tools—including SGM‑Consensus, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; FoldX is uncertain and therefore not counted. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is pathogenic. Taken together, the overwhelming majority of evidence indicates that D330Y is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250											-14.200	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	1.98	Ambiguous	0.6	2.90	Destabilizing	2.44	Destabilizing	0.35	Likely Benign	0.472	Likely Benign	-6.47	Deleterious	0.998	Probably Damaging	0.948	Probably Damaging	0.89	Pathogenic	0.00	Affected			0.0539	0.4689		-4	-3	2.2	48.09
c.1556A>T	E519V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight the discord: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates benign stability. Overall, the preponderance of evidence points to a pathogenic effect for E519V. This conclusion does not conflict with ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-10.513	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.59	Ambiguous	0.0	-0.40	Likely Benign	0.10	Likely Benign	0.16	Likely Benign	0.400	Likely Benign	-6.33	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	3.20	Benign	0.00	Affected			0.0825	0.4369		-2	-2	7.7	-29.98
c.1691A>C	E564A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564A 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 premPS and SIFT, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta remains 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 classification 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											-14.506	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.64	Ambiguous	0.1	1.49	Ambiguous	1.07	Ambiguous	0.24	Likely Benign	0.765	Likely Pathogenic	-5.91	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	-1.33	Pathogenic	0.12	Tolerated			0.3201	0.4918		0	-1	5.3	-58.04
c.1723C>A	R575S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R575S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include only SIFT, whereas the majority—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict pathogenicity. FoldX, Rosetta, Foldetta, and premPS give uncertain results, which are treated as unavailable evidence. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R575S, and this assessment 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	0.061840	Structured	0.021362	Uncertain	0.916	0.259	0.000											-11.124	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.1	0.55	Ambiguous	1.11	Ambiguous	0.76	Ambiguous	0.582	Likely Pathogenic	-2.71	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.21	Pathogenic	0.33	Tolerated			0.2669	0.2394		0	-1	3.7	-69.11
c.1769G>A	S590N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S590N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of other in silico predictors (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, PROVEAN, premPS, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) indicate a pathogenic or likely pathogenic impact. FoldX and Foldetta, which assess protein‑folding stability, return uncertain results and are therefore not considered evidence for either outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of pathogenic predictions strongly suggests that S590N is most likely pathogenic, a conclusion that is consistent with the absence of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022667	Structured	0.088943	Uncertain	0.918	0.199	0.000											-15.149	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	1.27	Ambiguous	0.1	2.10	Destabilizing	1.69	Ambiguous	1.48	Destabilizing	0.411	Likely Benign	-2.96	Deleterious	0.921	Possibly Damaging	0.598	Possibly Damaging	3.14	Benign	0.01	Affected			0.1254	0.4202		1	1	-2.7	27.03
c.1846G>T	D616Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D616Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SIFT, 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, also classifies the variant as 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 evidence from FoldX or Rosetta alone is conclusive. Overall, the balance of evidence favors a pathogenic interpretation, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000											-12.638	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	1.70	Ambiguous	0.3	1.32	Ambiguous	1.51	Ambiguous	0.35	Likely Benign	0.374	Likely Benign	-7.43	Deleterious	0.999	Probably Damaging	0.970	Probably Damaging	3.28	Benign	0.01	Affected			0.0465	0.4069		-4	-3	2.2	48.09
c.2007T>A	N669K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a Likely Pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-10.797	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.3	1.50	Ambiguous	0.95	Ambiguous	0.94	Ambiguous	0.243	Likely Benign	-5.35	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.03	Affected			0.2647	0.3312		1	0	-0.4	14.07
c.2007T>G	N669K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, FoldX, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus concurs, and the Foldetta stability analysis is inconclusive and therefore not used as evidence. No other tools provide definitive support for benignity. Consequently, the preponderance of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000											-10.797	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.3	1.50	Ambiguous	0.95	Ambiguous	0.94	Ambiguous	0.243	Likely Benign	-5.35	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.03	Affected			0.2647	0.3312		1	0	-0.4	14.07
c.2044T>G	Y682D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682D is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. The high‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic effect. With no ClinVar assertion to oppose these findings, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-15.094	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	2.81	Destabilizing	0.4	3.06	Destabilizing	2.94	Destabilizing	0.96	Ambiguous	0.639	Likely Pathogenic	-9.60	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.32	Benign	0.01	Affected			0.4191	0.0760		-4	-3	-2.2	-48.09
c.2108T>A	L703H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM‑Consensus itself is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts Pathogenic. Taken together, the overwhelming majority of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-12.886	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	2.52	Destabilizing	0.0	2.29	Destabilizing	2.41	Destabilizing	1.75	Destabilizing	0.420	Likely Benign	-5.71	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.09	Benign	0.00	Affected			0.1038	0.0288		-2	-3	-7.0	23.98
c.2771C>A	P924H 2D AIThe SynGAP1 missense variant P924H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of computational evidence indicates that P924H is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.236	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.457	Likely Benign	-5.87	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0.1317	0.3281		0	-2	-1.6	40.02
c.3476C>A	S1159Y 2D AIThe SynGAP1 missense variant S1159Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of evidence (six benign predictions versus five pathogenic, plus a benign consensus) points to a likely benign impact for S1159Y. 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		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-5.665	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-1.57	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.07	Tolerated			0.0567	0.4923		-3	-2	-0.5	76.10
c.3508A>C	S1170R 2D AIThe SynGAP1 missense variant S1170R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, but the high‑accuracy consensus is split. Thus, the variant is most likely pathogenic based on the preponderance of predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500											-1.451	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.475	Likely Benign	-1.89	Neutral	0.998	Probably Damaging	0.966	Probably Damaging	5.39	Benign	0.04	Affected			0.0770	0.3444		0	-1	-3.7	69.11
c.3510T>A	S1170R 2D AIThe SynGAP1 missense variant S1170R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of individual predictors lean toward pathogenicity, with the SGM‑Consensus providing a counter‑signal; the evidence is therefore inconclusive. The variant is most likely pathogenic according to the prevailing predictions, and this does not contradict ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500											-1.451	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.452	Likely Benign	-1.89	Neutral	0.998	Probably Damaging	0.966	Probably Damaging	5.39	Benign	0.04	Affected			0.0770	0.3444		0	-1	-3.7	69.11
c.3510T>G	S1170R 2D AIThe SynGAP1 missense variant S1170R is not 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 FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic, whereas the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional predictors lean toward pathogenicity, and the most accurate tools also favor a pathogenic classification, with no conflict from ClinVar or gnomAD data. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500											-1.451	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.452	Likely Benign	-1.89	Neutral	0.998	Probably Damaging	0.966	Probably Damaging	5.39	Benign	0.04	Affected			0.0770	0.3444		0	-1	-3.7	69.11
c.3719G>T	R1240L 2D AIThe SynGAP1 missense variant R1240L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, R1240L is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.541878	Disordered	0.511333	Binding	0.865	0.540	0.375											-10.181	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic										0.372	Likely Benign	-5.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.67	Pathogenic	0.00	Affected			0.1513	0.3394		-3	-2	8.3	-43.03
c.3818T>A	L1273Q 2D AIThe SynGAP1 missense variant L1273Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic and the SGM‑Consensus is labeled Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500											-6.813	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic										0.423	Likely Benign	-5.05	Deleterious	0.997	Probably Damaging	0.950	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.1139	0.1119		-2	-2	-7.3	14.97
c.1087T>A	Y363N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y363N 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 only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify Y363N 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 (majority vote) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the overwhelming agreement among 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	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-12.121	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	2.06	Destabilizing	0.1	2.85	Destabilizing	2.46	Destabilizing	1.45	Destabilizing	0.477	Likely Benign	-8.04	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.55	Pathogenic	0.01	Affected			0.3117	0.2021		-2	-2	-2.2	-49.07
c.1213C>G	R405G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.836	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	3.22	Destabilizing	0.5	3.26	Destabilizing	3.24	Destabilizing	1.38	Destabilizing	0.419	Likely Benign	-6.35	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.63	Benign	0.01	Affected			0.3381	0.4139		-3	-2	4.1	-99.14
c.1333G>A	E445K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E445K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic calls arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. When high‑accuracy methods are considered separately, AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence—including the high‑accuracy tools—supports a pathogenic effect. This conclusion does not conflict with ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.270205	Uncertain	0.947	0.228	0.000											-15.371	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.02	Likely Benign	0.0	0.02	Likely Benign	0.02	Likely Benign	0.46	Likely Benign	0.524	Likely Pathogenic	-3.82	Deleterious	0.991	Probably Damaging	0.951	Probably Damaging	3.35	Benign	0.02	Affected			0.1784	0.5311		0	1	-0.4	-0.94
c.1485A>C	E495D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E495D is listed in ClinVar with an uncertain significance (ClinVar ID 2000233.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions from SIFT and ESM1b, and pathogenic predictions from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN classifies the variant as likely pathogenic. AlphaMissense‑Optimized also predicts pathogenicity, whereas Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of deleterious impact. 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					Conflicting		2				-3.574	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic	1.39	Ambiguous	0.1	1.03	Ambiguous	1.21	Ambiguous	0.98	Ambiguous	0.566	Likely Pathogenic	-2.52	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.41	Pathogenic	0.17	Tolerated	3.37	35	0.1778	0.3064		3	2	0.0	-14.03	220.6	38.8	0.0	0.0	0.1	0.1		X		X				Uncertain	Glu495 is located in the α-helix (res. Leu489-Glu519), and its carboxylate group forms salt bridges with the neighboring Lys492 and with Arg596 on an opposing α-helix (res. Glu582-Met603) in the WT simulations. In the variant simulations, the acidic carboxylate side chain of Asp495 can also form salt bridges with both Lys492 and Arg596. However, the shorter side chain of aspartate tends to favor forming a salt bridge with the nearby Arg499 on the same α-helix instead. Asp495 might not maintain the salt bridge with Arg596 on the opposing α-helix as efficiently as Glu495 in the WT, potentially weakening the tertiary structure. Regardless, the potential negative effect is likely to be minor, with no deleterious effects observed on the protein structure during the simulations. However, due to its location at the GAP-Ras interface, the effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1485A>T	E495D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E495D is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from SIFT and ESM1b, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain or inconclusive results and are treated as unavailable. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta provides no definitive stability change. Overall, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.364496	Uncertain	0.933	0.161	0.000											-3.574	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic	1.39	Ambiguous	0.1	1.03	Ambiguous	1.21	Ambiguous	0.98	Ambiguous	0.566	Likely Pathogenic	-2.52	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	-1.41	Pathogenic	0.17	Tolerated	3.37	35	0.1778	0.3064		3	2	0.0	-14.03	220.6	38.8	0.0	0.0	0.1	0.1		X		X				Uncertain	Glu495 is located in the α-helix (res. Leu489-Glu519), and its carboxylate group forms salt bridges with the neighboring Lys492 and with Arg596 on an opposing α-helix (res. Glu582-Met603) in the WT simulations. In the variant simulations, the acidic carboxylate side chain of Asp495 can also form salt bridges with both Lys492 and Arg596. However, the shorter side chain of aspartate tends to favor forming a salt bridge with the nearby Arg499 on the same α-helix instead. Asp495 might not maintain the salt bridge with Arg596 on the opposing α-helix as efficiently as Glu495 in the WT, potentially weakening the tertiary structure. Regardless, the potential negative effect is likely to be minor, with no deleterious effects observed on the protein structure during the simulations. However, due to its location at the GAP-Ras interface, the effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1742G>T	R581L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R581L is not reported in ClinVar and is present in gnomAD (ID 6‑33440794‑G‑T). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and SIFT, whereas tools that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. In contrast, the Foldetta stability assessment, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of computational evidence supports a pathogenic classification for R581L, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.029544	Uncertain	0.829	0.236	0.000								6-33440794-G-T	3	1.86e-6	-10.134	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.1	-0.20	Likely Benign	0.05	Likely Benign	0.45	Likely Benign	0.654	Likely Pathogenic	-5.93	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.33	Pathogenic	0.08	Tolerated	3.37	34	0.1550	0.3483		-2	-3	8.3	-43.03
c.1892A>G	Q631R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q631R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions come from FoldX, Foldetta, and FATHMM, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact for Q631R, and this conclusion is not contradicted by 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											-14.881	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	-0.34	Likely Benign	0.1	0.83	Ambiguous	0.25	Likely Benign	0.77	Ambiguous	0.627	Likely Pathogenic	-3.98	Deleterious	0.973	Probably Damaging	0.969	Probably Damaging	2.77	Benign	0.01	Affected			0.1193	0.0653		1	1	-1.0	28.06
c.2036T>G	F679C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679C has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, whereas SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. FoldX and Foldetta are uncertain and are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta remains inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for F679C. This prediction is not contradicted by ClinVar status, which currently lacks any classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-10.269	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.65	Ambiguous	0.3	2.02	Destabilizing	1.84	Ambiguous	1.17	Destabilizing	0.532	Likely Pathogenic	-7.86	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.40	Benign	0.00	Affected			0.2344	0.0949		-4	-2	-0.3	-44.04
c.240A>C	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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 predicting pathogenicity, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.240A>T	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not listed in gnomAD. 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.3569G>T	S1190I 2D AIThe SynGAP1 missense change S1190I is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a pathogenic interpretation, and this assessment does not contradict any ClinVar annotation because no ClinVar record exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.455760	Uncertain	0.742	0.624	0.625											-4.842	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.371	Likely Benign	-1.89	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	5.26	Benign	0.04	Affected			0.0881	0.4175		-1	-2	5.3	26.08
c.3589G>A	E1197K 2D AIThe SynGAP1 E1197K missense change is not reported in ClinVar and has no gnomAD entry. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, whereas AlphaMissense‑Optimized predicts it to be Pathogenic; Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a benign effect, though the single high‑accuracy pathogenic prediction introduces uncertainty. The variant is most likely benign based on the current predictions, 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	Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250											-5.048	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.364	Likely Benign	-0.27	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	5.45	Benign	0.45	Tolerated			0.1512	0.5424		0	1	-0.4	-0.94
c.3606T>G	I1202M 2D AIThe SynGAP1 I1202M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the majority of high‑accuracy predictions, the variant is most likely pathogenic. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for I1202M. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-6.390	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-2.21	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	1.82	Pathogenic	0.03	Affected			0.0684	0.2165		2	1	-2.6	18.03
c.3800T>C	M1267T 2D AIThe SynGAP1 missense variant M1267T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) likewise indicates likely pathogenicity. No Foldetta stability prediction is available for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000											-5.315	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.270	Likely Benign	-5.00	Deleterious	0.982	Probably Damaging	0.672	Possibly Damaging	2.32	Pathogenic	0.00	Affected			0.2036	0.1934		-1	-1	-2.6	-30.09
c.556T>G	L186V 2D AIThe SynGAP1 missense variant L186V is not 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 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear majority and is therefore unavailable; Foldetta results are also unavailable. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate a pathogenic effect. There is no ClinVar entry to contradict this assessment, so 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.			0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-9.385	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic										0.090	Likely Benign	-2.27	Neutral	0.734	Possibly Damaging	0.185	Benign	3.60	Benign	0.00	Affected			0.1419	0.3665		2	1	0.4	-14.03
c.574G>A	A192T 2D AIThe SynGAP1 missense variant A192T has no ClinVar record (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic, 1 uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-7.562	In-Between	0.958	Likely Pathogenic	Likely Pathogenic										0.089	Likely Benign	-2.46	Neutral	0.978	Probably Damaging	0.714	Possibly Damaging	3.96	Benign	0.34	Tolerated			0.1148	0.5343		1	0	-2.5	30.03
c.581A>C	E194A 2D AIThe SynGAP1 missense variant E194A is not 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, 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—suggest that E194A is 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.			0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-7.101	In-Between	0.958	Likely Pathogenic	Likely Pathogenic										0.235	Likely Benign	-3.75	Deleterious	0.009	Benign	0.012	Benign	3.99	Benign	0.01	Affected			0.4331	0.5079		0	-1	5.3	-58.04
c.640C>A	L214M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L214M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are PROVEAN and FATHMM, whereas the majority of tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; the remaining tools (FoldX, Rosetta, Foldetta, premPS) are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs two benign) and Foldetta is uncertain. Thus, the available evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-9.347	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.3	1.43	Ambiguous	1.09	Ambiguous	0.80	Ambiguous	0.646	Likely Pathogenic	-1.72	Neutral	0.997	Probably Damaging	0.916	Probably Damaging	5.73	Benign	0.01	Affected			0.0805	0.4054		4	2	-1.9	18.03
c.731A>G	E244G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of computational evidence points to the variant being most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-10.452	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.28	Ambiguous	0.0	0.74	Ambiguous	1.01	Ambiguous	1.01	Destabilizing	0.900	Likely Pathogenic	-5.67	Deleterious	0.990	Probably Damaging	0.815	Possibly Damaging	5.73	Benign	0.01	Affected			0.2266	0.5252		0	-2	3.1	-72.06
c.844T>A	C282S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the majority of other in‑silico predictors (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as pathogenic. Stability‑based methods (FoldX, Rosetta, and Foldetta) return uncertain results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000					Uncertain		1				-11.846	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.1	1.23	Ambiguous	1.39	Ambiguous	1.62	Destabilizing	0.460	Likely Benign	-9.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.64	Pathogenic	0.03	Affected	3.39	18	0.5009	0.1286	Weaken	0	-1	-3.3	-16.06	233.2	14.8	-0.1	0.0	-0.2	0.3						X		Potentially Benign	The thiol-containing side chain of Cys282, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), packs against multiple hydrophobic residues (e.g., Ile268, Leu284, Trp308, Leu327). In the variant simulations, the hydroxyl-containing side chain of Ser282 is more hydrophilic and, hence, not as favorable as Cys282 for this hydrophobic niche. Due to this polarity difference, the residue swap could potentially weaken the hydrophobic packing of the C2 domain during the folding process.Moreover, because the C2 domain interacts with the membrane, there could also be a negative effect on the stability of the SynGAP-membrane association. However, no large-scale structural changes were observed during the variant simulations. The hydroxyl group of Ser282 forms a hydrogen bond with the backbone carbonyl group of His326 in another β strand (res. Ala322-Arg329), which competes directly with the backbone amide group of Glu283 within the secondary structure element.
c.845G>C	C282S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions from FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. 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 status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000											-11.846	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.1	1.23	Ambiguous	1.39	Ambiguous	1.62	Destabilizing	0.436	Likely Benign	-9.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.64	Pathogenic	0.03	Affected	3.39	18	0.5009	0.1286	Weaken	0	-1	-3.3	-16.06	233.2	14.8	-0.1	0.0	-0.2	0.3						X		Potentially Benign	The thiol-containing side chain of Cys282, located at the beginning of an anti-parallel β sheet strand (res. Arg279-Leu286), packs against multiple hydrophobic residues (e.g., Ile268, Leu284, Trp308, Leu327). In the variant simulations, the hydroxyl-containing side chain of Ser282 is more hydrophilic and, hence, not as favorable as Cys282 for this hydrophobic niche. Due to this polarity difference, the residue swap could potentially weaken the hydrophobic packing of the C2 domain during the folding process.Moreover, because the C2 domain interacts with the membrane, there could also be a negative effect on the stability of the SynGAP-membrane association. However, no large-scale structural changes were observed during the variant simulations. The hydroxyl group of Ser282 forms a hydrogen bond with the backbone carbonyl group of His326 in another β strand (res. Ala322-Arg329), which competes directly with the backbone amide group of Glu283 within the secondary structure element.
c.953C>T	P318L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P318L is listed in ClinVar with an uncertain significance (ClinVar ID 956570.0) and is present in gnomAD (6‑33437858‑C‑T). Functional prediction tools that agree on a benign effect are Rosetta and premPS. The remaining tools—REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized reports pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Taken together, the preponderance of evidence points to a pathogenic effect for P318L, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000					Uncertain		3	6-33437858-C-T	3	1.86e-6	-10.090	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic	1.33	Ambiguous	0.1	0.26	Likely Benign	0.80	Ambiguous	0.43	Likely Benign	0.624	Likely Pathogenic	-8.96	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.82	Pathogenic	0.03	Affected	3.38	23	0.2166	0.6941		-3	-3	5.4	16.04	228.6	-68.9	-0.7	0.7	-0.4	0.1						X		Potentially Benign	The cyclic five-membered pyrrolidine ring of Pro318, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Asp330-Ala322, res. Thr305-Asn315), packs against the hydrophobic side chain of Ile205 at the end of the anti-parallel β sheet in the PH domain. In the variant simulations, the iso-butyl side chain of Leu318 is unable to do the same, potentially weakening the PH and C2 domain association. Importantly, the residue swap could also affect loop formation during folding, as proline can make tighter turns than leucine. Because the residue swap could affect the C2 domain stability, it could also negatively impact the SynGAP-membrane association.
c.1421A>G	D474G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D474G is not reported in ClinVar and is present in gnomAD (ID 6‑33438453‑A‑G). Functional prediction tools show a split: benign calls come from FoldX, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta remains uncertain. High‑accuracy assessments give a pathogenic verdict from AlphaMissense‑Optimized and a pathogenic consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the majority of evidence points to a pathogenic effect, 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	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000								6-33438453-A-G	1	6.20e-7	-11.215	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic	-0.38	Likely Benign	0.0	0.82	Ambiguous	0.22	Likely Benign	0.44	Likely Benign	0.823	Likely Pathogenic	-6.13	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.28	Pathogenic	0.07	Tolerated	3.37	34	0.3245	0.4933		-1	1	3.1	-58.04
c.158G>T	G53V 2D AIThe SynGAP1 missense variant G53V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.308	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.238	Likely Benign	-1.71	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.11	Benign	0.00	Affected			0.1193	0.4833		-1	-3	4.6	42.08
c.2473T>C	S825P 2D AIThe SynGAP1 missense variant S825P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S825P is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750											-3.227	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.285	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.94	Pathogenic	0.02	Affected			0.2060	0.5998		1	-1	-0.8	10.04
c.3526G>A	E1176K 2D AIThe SynGAP1 E1176K missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Benign. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) is not available for this residue. Because the majority of evidence, including the consensus score, points to a benign effect and no ClinVar entry contradicts this, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.572075	Binding	0.525	0.715	0.250											-4.240	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.400	Likely Benign	-1.41	Neutral	0.995	Probably Damaging	0.949	Probably Damaging	5.54	Benign	0.18	Tolerated			0.1658	0.6321		0	1	-0.4	-0.94
c.3588G>C	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus indicates benignity; a Foldetta stability analysis is unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.3588G>T	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further divide the evidence: AlphaMissense‑Optimized predicts a pathogenic effect, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. With no ClinVar classification to resolve the conflict, the overall computational signal is inconclusive, but the presence of a pathogenic prediction from a high‑accuracy model and the absence of a benign consensus suggest the variant is more likely pathogenic. This assessment does not contradict any ClinVar status, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.466T>A	F156I 2D AIThe SynGAP1 missense variant F156I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Consequently, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-10.505	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.38	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.99	Benign	0.00	Affected			0.1960	0.1938		1	0	1.7	-34.02
c.937G>A	E313K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E313K is listed in ClinVar as Benign (ClinVar ID 3695040.0) and is not reported in gnomAD. Prediction tools that report a benign effect are absent; all available predictors that provide a definitive call classify the variant as pathogenic. These include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, the SGM‑Consensus indicates Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is Uncertain. Based on the overwhelming pathogenic predictions, 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	C2	0.170161	Structured	0.366526	Uncertain	0.898	0.304	0.125					Likely Benign		1				-12.902	Likely Pathogenic	0.959	Likely Pathogenic	Likely Pathogenic	0.64	Ambiguous	0.6	1.40	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.575	Likely Pathogenic	-3.31	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	1.90	Pathogenic	0.02	Affected			0.2540	0.7708		0	1	-0.4	-0.94
c.1360A>T	I454F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I454F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM. All other evaluated algorithms—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. premPS is uncertain and does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the absence of benign evidence, the variant is most likely pathogenic, with no ClinVar status to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.312811	Uncertain	0.965	0.182	0.000											-12.468	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	4.15	Destabilizing	0.7	2.96	Destabilizing	3.56	Destabilizing	0.70	Ambiguous	0.464	Likely Benign	-3.95	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.33	Benign	0.00	Affected			0.0422	0.2560		1	0	-1.7	34.02
c.1534G>A	E512K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E512K missense variant is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, FATHMM, premPS, and Foldetta, while those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, seven tools predict pathogenicity versus six predicting benignity, with one uncertain result. Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.247079	Uncertain	0.923	0.273	0.000											-13.927	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.17	Likely Benign	0.1	0.63	Ambiguous	0.40	Likely Benign	-0.03	Likely Benign	0.344	Likely Benign	-3.85	Deleterious	0.962	Probably Damaging	0.658	Possibly Damaging	3.32	Benign	0.06	Tolerated			0.2844	0.4776		0	1	-0.4	-0.94
c.1590G>C	K530N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10/13) support pathogenicity, with only three tools indicating benign. Therefore, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.459	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.23	Likely Benign	0.33	Likely Benign	0.56	Ambiguous	0.553	Likely Pathogenic	-4.18	Deleterious	0.950	Possibly Damaging	0.703	Possibly Damaging	-1.65	Pathogenic	0.00	Affected			0.2350	0.1086		1	0	0.4	-14.07
c.1590G>T	K530N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10/13) support pathogenicity, with only three tools indicating benign. Therefore, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.459	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.23	Likely Benign	0.33	Likely Benign	0.56	Ambiguous	0.553	Likely Pathogenic	-4.18	Deleterious	0.950	Possibly Damaging	0.703	Possibly Damaging	-1.65	Pathogenic	0.00	Affected			0.2350	0.1086		1	0	0.4	-14.07
c.1757A>C	D586A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D586A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include FoldX, SIFT, and premPS, whereas a majority of predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains inconclusive. No evidence from the uncertain tools (Rosetta, Foldetta) alters this consensus. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-9.955	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.41	Likely Benign	0.2	0.88	Ambiguous	0.65	Ambiguous	0.25	Likely Benign	0.693	Likely Pathogenic	-4.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.22	Pathogenic	0.31	Tolerated			0.3397	0.4673		0	-2	5.3	-44.01
c.176T>G	L59R 2D AISynGAP1 missense variant L59R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. The predictions are therefore split, with an equal number of benign and pathogenic calls, and the high‑accuracy tools provide contradictory signals. Consequently, the variant is most likely pathogenic based on the presence of multiple pathogenic predictions and the high‑accuracy AlphaMissense‑Optimized result, 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 Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-4.037	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.266	Likely Benign	-2.09	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.26	Benign	0.00	Affected			0.1298	0.0600		-3	-2	-8.3	43.03
c.1775C>T	S592L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S592L is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools show a predominance of pathogenic calls: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict deleterious effects, whereas benign predictions are limited to Foldetta, premPS, and SIFT. Uncertain results are reported only by FoldX and Rosetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenicity, SGM Consensus confirms a pathogenic status, and Foldetta, a protein‑folding stability method, predicts a benign effect. Overall, the preponderance of evidence indicates that S592L is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.100070	Uncertain	0.913	0.182	0.000											-12.948	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.94	Ambiguous	0.3	-1.89	Ambiguous	-0.48	Likely Benign	0.50	Likely Benign	0.711	Likely Pathogenic	-5.57	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	-1.12	Pathogenic	0.25	Tolerated			0.1089	0.4367		-3	-2	4.6	26.08
c.1829T>A	L610H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610H 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	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000											-14.573	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	4.83	Destabilizing	0.5	4.98	Destabilizing	4.91	Destabilizing	2.03	Destabilizing	0.927	Likely Pathogenic	-6.91	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.59	Pathogenic	0.00	Affected			0.1067	0.0741		-2	-3	-7.0	23.98
c.1970G>T	W657L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant W657L is listed in ClinVar with an uncertain significance (ClinVar ID 2767440.0) and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, ESM1b, and AlphaMissense‑Default. Uncertain predictions come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta predicts a benign folding‑stability change. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the ClinVar uncertain status but leans toward pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000					Uncertain		1				-14.411	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.14	Likely Benign	0.1	0.73	Ambiguous	0.44	Likely Benign	0.87	Ambiguous	0.213	Likely Benign	-10.86	Deleterious	0.277	Benign	0.078	Benign	3.52	Benign	0.14	Tolerated	3.39	24	0.2302	0.2049		-2	-2	4.7	-73.05
c.322A>G	K108E 2D AIThe SynGAP1 K108E missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the predictions are split evenly between benign and pathogenic, with no clear majority. Consequently, the variant’s impact remains uncertain, and there is no contradiction with ClinVar status, which currently lists no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.679	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-1.24	Neutral	0.993	Probably Damaging	0.956	Probably Damaging	4.12	Benign	0.04	Affected			0.4145	0.1166		0	1	0.4	0.94
c.3405G>C	K1135N 2D AIThe SynGAP1 missense variant K1135N is listed in ClinVar (ID 633521.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. In contrast, AlphaMissense‑Default and AlphaMissense‑Optimized both predict a pathogenic outcome. High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions support a benign classification, which does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875					Uncertain		1				-5.715	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-0.97	Neutral	0.411	Benign	0.321	Benign	5.43	Benign	0.07	Tolerated	4.32	2	0.4152	0.1793		1	0	0.4	-14.07
c.3405G>T	K1135N 2D AIThe SynGAP1 missense variant K1135N is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443957‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, 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 likely benign; Foldetta results are unavailable. Overall, the majority of predictions (seven benign vs. two pathogenic) support a benign interpretation. This consensus does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875								6-33443957-G-T			-5.715	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-0.97	Neutral	0.411	Benign	0.321	Benign	5.43	Benign	0.07	Tolerated	4.32	2	0.4152	0.1793		1	0	0.4	-14.07
c.3548A>G	Y1183C 2D AIThe SynGAP1 missense variant Y1183C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500											-5.585	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.261	Likely Benign	-2.69	Deleterious	0.999	Probably Damaging	0.917	Probably Damaging	2.76	Benign	0.06	Tolerated			0.3449	0.1955		0	-2	3.8	-60.04
c.3564T>A	D1188E 2D AIThe SynGAP1 missense variant D1188E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic interpretation. The variant is most likely pathogenic based on the consensus of computational tools, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-2.517	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-1.93	Neutral	0.992	Probably Damaging	0.992	Probably Damaging	5.50	Benign	0.00	Affected			0.0954	0.4616		3	2	0.0	14.03
c.3564T>G	D1188E 2D AIThe SynGAP1 missense variant D1188E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy predictors give a mixed picture: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this residue. Overall, five of the nine evaluated tools predict pathogenicity while four predict benignity, with the high‑accuracy AlphaMissense‑Optimized result supporting the pathogenic prediction. Therefore, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-2.517	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.382	Likely Benign	-1.93	Neutral	0.992	Probably Damaging	0.992	Probably Damaging	5.50	Benign	0.00	Affected			0.0954	0.4616		3	2	0.0	14.03
c.3584T>C	V1195A 2D AIThe SynGAP1 missense variant V1195A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default both 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 pathogenic, whereas the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.604312	Disordered	0.434133	Uncertain	0.842	0.603	0.250											-4.291	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.421	Likely Benign	-0.84	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.60	Benign	0.44	Tolerated			0.2602	0.1854		0	0	-2.4	-28.05
c.3734A>C	E1245A 2D AIThe SynGAP1 missense variant E1245A is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL is the sole tool that predicts a benign effect, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus likewise indicates a likely pathogenic effect. Foldetta results are not available for this variant. Overall, the consensus of the available predictions indicates that E1245A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.433	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic										0.311	Likely Benign	-4.85	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.2555	0.5721		0	-1	5.3	-58.04
c.3774G>C	Q1258H 2D AIThe SynGAP1 missense variant Q1258H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also leans pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-5.465	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-3.99	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.0735	0.3066		3	0	0.3	9.01
c.3774G>T	Q1258H 2D AIThe SynGAP1 missense variant Q1258H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-5.465	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-3.99	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.95	Pathogenic	0.00	Affected			0.0735	0.3066		3	0	0.3	9.01
c.650A>C	E217A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E217A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, AlphaMissense‑Default, and AlphaMissense‑Optimized. Four tools (FoldX, Rosetta, Foldetta, and ESM1b) returned uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; Foldetta’s stability prediction is uncertain. Overall, the majority of available predictions support a pathogenic impact for E217A. This conclusion is not contradicted by ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.278302	Structured	0.404912	Uncertain	0.823	0.284	0.000											-7.294	In-Between	0.960	Likely Pathogenic	Likely Pathogenic	0.67	Ambiguous	0.5	0.61	Ambiguous	0.64	Ambiguous	0.50	Likely Benign	0.619	Likely Pathogenic	-3.88	Deleterious	0.900	Possibly Damaging	0.307	Benign	5.81	Benign	0.12	Tolerated			0.4442	0.8090		0	-1	5.3	-58.04
c.670A>C	T224P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T224P 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 are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b) all predict a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.360921	Uncertain	0.848	0.315	0.125											-11.812	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	3.63	Destabilizing	0.4	2.68	Destabilizing	3.16	Destabilizing	0.57	Ambiguous	0.765	Likely Pathogenic	-3.65	Deleterious	0.971	Probably Damaging	0.543	Possibly Damaging	5.56	Benign	0.23	Tolerated			0.2355	0.6063		0	-1	-0.9	-3.99
c.1282T>C	Y428H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y428H is not reported in ClinVar but is present in gnomAD (ID 6‑33438187‑T‑C). Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM Consensus score (Likely Pathogenic) all suggest a deleterious impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Consequently, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000								6-33438187-T-C	1	6.19e-7	-8.566	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	3.18	Destabilizing	0.1	2.20	Destabilizing	2.69	Destabilizing	1.80	Destabilizing	0.458	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.04	Affected	3.38	25	0.2685	0.0711		2	0	-1.9	-26.03
c.1376G>C	G459A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G459A missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Predictions labeled Uncertain (Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is Uncertain and therefore not considered evidence. Overall, the majority of reliable tools indicate a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.289888	Uncertain	0.903	0.150	0.125											-11.684	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	2.44	Destabilizing	0.1	0.90	Ambiguous	1.67	Ambiguous	0.72	Ambiguous	0.469	Likely Benign	-5.63	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.06	Benign	0.01	Affected			0.3529	0.5161		1	0	2.2	14.03
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	0.40	Likely Benign	0.1	1.08	Ambiguous	0.74	Ambiguous	0.83	Ambiguous	0.768	Likely Pathogenic	-3.45	Deleterious	0.996	Probably Damaging	0.987	Probably Damaging	-1.26	Pathogenic	0.11	Tolerated	3.37	34	0.1828	0.6813		1	0	-0.4	-0.94
c.1451T>A	F484Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FATHMM, and polyPhen‑2 HumVar, whereas the majority of other in silico predictors (SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect. Stability‑based methods FoldX and Rosetta are inconclusive, and Foldetta likewise reports no definitive change. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence supports a pathogenic classification for F484Y, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-14.223	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	1.70	Ambiguous	0.1	0.92	Ambiguous	1.31	Ambiguous	1.26	Destabilizing	0.356	Likely Benign	-2.92	Deleterious	0.733	Possibly Damaging	0.344	Benign	2.66	Benign	0.02	Affected			0.1056	0.1595		7	3	-4.1	16.00
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	0.38	Likely Benign	0.1	1.77	Ambiguous	1.08	Ambiguous	0.76	Ambiguous	0.743	Likely Pathogenic	-3.58	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	-1.40	Pathogenic	0.04	Affected			0.1810	0.3528		0	1	-0.4	-0.94
c.1573G>C	E525Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E525Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely disagree: benign predictions come from Rosetta, Foldetta, and FATHMM, while pathogenic predictions are returned by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-13.722	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	1.05	Ambiguous	0.7	-0.11	Likely Benign	0.47	Likely Benign	0.84	Ambiguous	0.516	Likely Pathogenic	-2.98	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	2.68	Benign	0.00	Affected			0.1173	0.3962		2	2	0.0	-0.98
c.1712C>G	S571W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S571W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that provide a clear verdict overwhelmingly classify the substitution as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict deleterious effects. No tool in the dataset returned a benign classification; the only non‑conclusive results come from FoldX, Rosetta, Foldetta, and premPS, which are listed as uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta’s stability analysis is inconclusive. Based on the aggregate predictions, the variant is most likely pathogenic, and this assessment is consistent with the absence of a ClinVar entry (no contradictory status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.045569	Uncertain	0.928	0.270	0.000											-14.025	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	-1.13	Ambiguous	0.1	-1.44	Ambiguous	-1.29	Ambiguous	0.67	Ambiguous	0.867	Likely Pathogenic	-6.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.32	Pathogenic	0.00	Affected			0.0648	0.3809		-2	-3	-0.1	99.14
c.2174T>G	L725R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, Rosetta, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. FoldX and Foldetta report uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, while Foldetta remains uncertain. Based on the overwhelming majority of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-15.383	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.3	2.16	Destabilizing	1.43	Ambiguous	1.49	Destabilizing	0.345	Likely Benign	-5.46	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			0.1374	0.0846		-3	-2	-8.3	43.03
c.2533G>A	D845N 2D AIThe SynGAP1 missense variant D845N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized remains pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.586	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-3.42	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.1216	0.7112		2	1	0.0	-0.98
c.2770C>A	P924T 2D AIThe SynGAP1 missense variant P924T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that P924T is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.360	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.400	Likely Benign	-6.03	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1190	0.4009		0	-1	0.9	3.99
c.318G>C	R106S 2D AIThe SynGAP1 missense variant R106S is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as benign, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence. Thus, the variant is most likely benign based on the collective predictions, 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											-2.651	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-1.87	Neutral	0.131	Benign	0.026	Benign	3.68	Benign	0.00	Affected			0.3050	0.4129		0	-1	3.7	-69.11
c.318G>T	R106S 2D AIThe SynGAP1 missense variant R106S is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as benign, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, but the high‑accuracy tools provide conflicting evidence. Thus, the variant is most likely benign based on the collective predictions, 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											-2.651	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-1.87	Neutral	0.131	Benign	0.026	Benign	3.68	Benign	0.00	Affected			0.3050	0.4129		0	-1	3.7	-69.11
c.3214A>G	K1072E 2D AIThe SynGAP1 missense variant K1072E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are returned by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments indicate that AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (derived from the same set of predictors) labels it as likely benign. No Foldetta stability analysis is available for this residue. Overall, the majority of tools lean toward a benign effect, but the presence of pathogenic calls from several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of evidence, 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	0.984675	Binding	0.307	0.907	0.750											-3.889	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-0.90	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.96	Benign	0.08	Tolerated			0.3636	0.1874		0	1	0.4	0.94
c.3535A>G	K1179E 2D AIThe SynGAP1 missense variant K1179E is reported in gnomAD (ID 6‑33444570‑A‑G) but has no ClinVar entry. 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 and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of individual predictors (five versus four) lean toward pathogenicity, and the high‑accuracy AlphaMissense‑Optimized result supports this. No ClinVar status is available to contradict these findings. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250								6-33444570-A-G	1	6.20e-7	-4.040	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.143	Likely Benign	-1.02	Neutral	0.800	Possibly Damaging	0.525	Possibly Damaging	2.96	Benign	0.00	Affected	4.32	2	0.3476	0.0876		1	0	0.4	0.94
c.3548A>C	Y1183S 2D AIThe SynGAP1 missense variant Y1183S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, PROVEAN, SIFT, ESM1b, FATHMM) and pathogenic predictions (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact for Y1183S, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500											-2.514	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-1.57	Neutral	0.951	Possibly Damaging	0.619	Possibly Damaging	2.86	Benign	0.51	Tolerated			0.5346	0.1096	Weaken	-3	-2	0.5	-76.10
c.3680A>C	E1227A 2D AIThe SynGAP1 missense variant E1227A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-9.111	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.341	Likely Benign	-4.63	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.29	Pathogenic	0.00	Affected			0.3142	0.6025		0	-1	5.3	-58.04
c.403C>G	R135G 2D AIThe SynGAP1 missense variant R135G is not reported in ClinVar and is absent from gnomAD. Consensus from standard in silico predictors shows a split: benign calls come from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments give a pathogenic result from AlphaMissense‑Optimized, an inconclusive SGM Consensus (a 2‑vs‑2 vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and no Foldetta data. Because the majority of tools predict benign and the high‑accuracy methods are either pathogenic or inconclusive, the overall evidence leans toward a benign effect. This conclusion does not conflict with the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-5.799	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.240	Likely Benign	-3.17	Deleterious	0.000	Benign	0.000	Benign	3.69	Benign	0.01	Affected			0.3559	0.3273		-3	-2	4.1	-99.14
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	-3.21	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.90	Benign	0.00	Affected			0.1881	0.3847		0	-2	-1.6	40.02
c.509G>T	R170L 2D AIThe SynGAP1 missense variant R170L has no ClinVar entry and is not reported in gnomAD. In silico predictors fall into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of pathogenic predictions, including the high‑accuracy consensus, suggests that R170L is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-8.649	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-4.02	Deleterious	0.798	Possibly Damaging	0.319	Benign	3.87	Benign	0.00	Affected			0.1561	0.4310		-3	-2	8.3	-43.03
c.581A>G	E194G 2D AIThe SynGAP1 missense variant E194G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion 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		0.418646	Structured	0.430723	Uncertain	0.346	0.551	0.125											-9.136	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic										0.316	Likely Benign	-4.47	Deleterious	0.580	Possibly Damaging	0.196	Benign	3.96	Benign	0.01	Affected			0.3633	0.4616		0	-2	3.1	-72.06
c.616A>T	I206F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I206F 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 polyPhen‑2 HumVar. Those that predict a pathogenic effect comprise SGM‑Consensus, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Rosetta. Predictions that are uncertain or inconclusive are FoldX and premPS. High‑accuracy methods all support a deleterious outcome: 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. 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	PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-12.669	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	1.82	Ambiguous	0.4	3.39	Destabilizing	2.61	Destabilizing	0.70	Ambiguous	0.133	Likely Benign	-3.40	Deleterious	0.838	Possibly Damaging	0.368	Benign	3.64	Benign	0.01	Affected			0.0428	0.2721		1	0	-1.7	34.02
c.781G>C	D261H 2D AIThe SynGAP1 missense variant D261H 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 premPS and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; Rosetta is uncertain and is treated as unavailable. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic (3 pathogenic vs. 1 benign); and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Thus, 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	C2	0.284882	Structured	0.422514	Uncertain	0.883	0.264	0.125											-13.688	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	4.33	Destabilizing	3.2	0.93	Ambiguous	2.63	Destabilizing	0.33	Likely Benign	0.780	Likely Pathogenic	-3.67	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	6.04	Benign	0.01	Affected			0.0937	0.5465		1	-1	0.3	22.05
c.1234T>G	L412V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L412V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-11.726	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.65	Destabilizing	0.0	3.52	Destabilizing	3.59	Destabilizing	1.54	Destabilizing	0.231	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.25	Benign	0.01	Affected			0.1275	0.3378		2	1	0.4	-14.03
c.1372A>C	T458P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T458P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, while the remaining tools (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, ESM1b, and the SGM‑Consensus) all predict a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a pathogenic effect. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-13.547	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.05	Destabilizing	0.2	5.36	Destabilizing	4.21	Destabilizing	0.78	Ambiguous	0.557	Likely Pathogenic	-5.33	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.06	Tolerated			0.2098	0.5395		0	-1	-0.9	-3.99
c.1423C>T	R475W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R475W is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438455‑C‑T). Prediction tools that agree on a benign effect include only Foldetta, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) uniformly predict a pathogenic impact; FoldX, Rosetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification but suggests that the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.382696	Uncertain	0.852	0.261	0.000					Uncertain		1	6-33438455-C-T	1	6.20e-7	-13.235	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	1.44	Ambiguous	0.4	-0.92	Ambiguous	0.26	Likely Benign	0.56	Ambiguous	0.725	Likely Pathogenic	-7.56	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	-1.45	Pathogenic	0.00	Affected	3.39	28	0.1231	0.2785		2	-3	3.6	30.03	266.9	39.6	0.0	0.0	0.0	0.1	X	X		X				Potentially Pathogenic	In the WT simulations, the guanidinium group of Arg475, located near the end of an α-helix (res. Ala461-Phe476), stacks with the phenyl ring of Phe476 and forms a salt bridge with Glu472. Additionally, Arg475 occasionally forms another salt bridge with the carboxylate group of Glu486 on the α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. Therefore, Arg475 potentially plays a key role in positioning the loop by interacting with Glu486, which is necessary for the positioning of the “arginine finger” (Arg485) and, ultimately, for RasGTPase activation.In the variant simulations, Trp475 moves and stacks with Arg479 on the proceeding α-α loop, disrupting the terminal end of the α-helix. Lastly, the potential effect of the residue swap on the SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1426T>A	F476I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F476I has no ClinVar entry and is not reported in gnomAD. Functional prediction tools fall into two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, and FATHMM; pathogenic predictions come from FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive and is treated as unavailable. With seven tools indicating pathogenicity versus five indicating benign, and two high‑accuracy tools supporting pathogenicity, the evidence points to a likely pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-12.617	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.90	Destabilizing	0.1	3.09	Destabilizing	3.50	Destabilizing	0.39	Likely Benign	0.239	Likely Benign	-1.23	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.50	Benign	0.37	Tolerated			0.1383	0.2202		1	0	1.7	-34.02
c.149T>A	I50N 2D AIThe SynGAP1 missense variant I50N is not 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 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign. Foldetta results are unavailable. Overall, the predictions are mixed, with an equal split between benign and pathogenic calls, but the most reliable single‑tool prediction (AlphaMissense‑Optimized) and the majority of individual tools lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.295083	Structured	0.449965	Uncertain	0.545	0.708	0.000											-7.091	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.135	Likely Benign	-2.37	Neutral	0.842	Possibly Damaging	0.272	Benign	3.73	Benign	0.00	Affected			0.0824	0.0412		-2	-3	-8.0	0.94
c.1540A>T	I514F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I514F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—report it as pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity; 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 stability calculations, classifies the variant as pathogenic. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which is consistent with its ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.049374	Structured	0.221408	Uncertain	0.948	0.266	0.000					Uncertain		1				-13.383	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.35	Destabilizing	0.3	3.74	Destabilizing	3.05	Destabilizing	0.93	Ambiguous	0.601	Likely Pathogenic	-3.98	Deleterious	0.997	Probably Damaging	0.993	Probably Damaging	2.89	Benign	0.00	Affected	3.37	35	0.0574	0.1629		0	1	-1.7	34.02
c.1547C>T	A516V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A516V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect fall into two groups: benign predictions come from FoldX, Rosetta, and SIFT, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of tools, including the high‑accuracy predictors, lean toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000											-11.545	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.16	Likely Benign	0.29	Likely Benign	0.62	Ambiguous	0.639	Likely Pathogenic	-3.61	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.32	Pathogenic	0.09	Tolerated			0.1336	0.5263		0	0	2.4	28.05
c.1624A>C	N542H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542H is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence supports a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.053060	Structured	0.026143	Uncertain	0.953	0.331	0.000											-10.983	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.06	Likely Benign	0.1	-0.12	Likely Benign	-0.03	Likely Benign	0.46	Likely Benign	0.791	Likely Pathogenic	-3.91	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.44	Pathogenic	0.05	Affected			0.1137	0.5368		2	1	0.3	23.04
c.1738G>T	G580C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580C is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic outcome include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Rosetta and premPS. High‑accuracy methods all support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No tool predicts benign. **Based on the consensus of available predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status (which is currently unreported).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-11.608	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.94	Destabilizing	0.1	1.18	Ambiguous	2.06	Destabilizing	0.60	Ambiguous	0.755	Likely Pathogenic	-8.66	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.18	Pathogenic	0.01	Affected			0.1422	0.2146		-3	-3	2.9	46.09
c.1751T>A	I584N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I584N 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 pathogenic impact. 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	0.059222	Structured	0.046673	Uncertain	0.846	0.244	0.000											-13.153	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.70	Destabilizing	0.1	2.13	Destabilizing	2.42	Destabilizing	2.08	Destabilizing	0.706	Likely Pathogenic	-6.57	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.18	Pathogenic	0.01	Affected			0.0693	0.0470		-2	-3	-8.0	0.94
c.1813C>G	P605A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic, while premPS remains uncertain. High‑accuracy assessments corroborate this trend: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenic. No tool predicts a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000											-10.085	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.58	Destabilizing	0.3	2.42	Destabilizing	2.50	Destabilizing	0.91	Ambiguous	0.744	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.75	Pathogenic	0.00	Affected			0.3432	0.4607		1	-1	3.4	-26.04
c.2517G>C	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2517G>T	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2531T>C	L844P 2D AIThe SynGAP1 missense variant L844P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessment further supports a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both conventional and high‑accuracy tools indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375											-7.425	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.319	Likely Benign	-3.18	Deleterious	0.986	Probably Damaging	0.876	Possibly Damaging	2.58	Benign	0.01	Affected			0.3528	0.1458		-3	-3	-5.4	-16.04
c.271G>A	E91K 2D AISynGAP1 E91K is not reported in ClinVar and is absent from gnomAD. Computational predictors fall into two groups: benign calls (REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus “Likely Benign”) and pathogenic calls (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy tools give conflicting results: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts benign; Foldetta data are unavailable. Consequently, the evidence is split, but the consensus of the most reliable predictors leans toward a benign effect. Thus, 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		0.575842	Disordered	0.533667	Binding	0.303	0.875	0.500											-4.964	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-1.07	Neutral	0.880	Possibly Damaging	0.636	Possibly Damaging	3.92	Benign	0.00	Affected			0.2693	0.7444		0	1	-0.4	-0.94
c.3485C>T	P1162L 2D AIThe SynGAP1 missense variant P1162L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. four benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375											-3.370	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.68	Benign	0.06	Tolerated			0.2153	0.7372		-3	-3	5.4	16.04
c.3562G>A	D1188N 2D AIThe SynGAP1 D1188N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification for D1188N, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.476583	Structured	0.484322	Uncertain	0.687	0.626	0.625											-5.621	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.340	Likely Benign	-2.50	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	5.47	Benign	0.00	Affected			0.0767	0.4663		2	1	0.0	-0.98
c.3659A>G	E1220G 2D AIThe SynGAP1 missense variant E1220G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign change, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that E1220G is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.444845	Uncertain	0.881	0.551	0.375											-12.121	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.454	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.61	Pathogenic	0.00	Affected			0.2791	0.4030		0	-2	3.1	-72.06
c.3784A>C	I1262L 2D AIThe SynGAP1 missense variant I1262L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (pathogenic), and PROVEAN (benign)—also indicates pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact for I1262L, 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.		Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-7.334	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.269	Likely Benign	-1.66	Neutral	0.981	Probably Damaging	0.970	Probably Damaging	1.94	Pathogenic	0.00	Affected			0.0735	0.3246		2	2	-0.7	0.00
c.3788T>C	I1263T 2D AIThe SynGAP1 missense variant I1263T is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33446780‑T‑C). Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report pathogenicity, while only ESM1b predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a pathogenic effect, which aligns with the ClinVar designation of uncertainty but does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000					Uncertain		1	6-33446780-T-C	2	1.24e-6	-6.564	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.529	Likely Pathogenic	-4.15	Deleterious	0.946	Possibly Damaging	0.673	Possibly Damaging	1.81	Pathogenic	0.00	Affected	3.77	5	0.1221	0.1051		0	-1	-5.2	-12.05
c.4001A>T	N1334I 2D AIThe SynGAP1 missense variant N1334I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the balance of evidence (seven pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.915074	Disordered	0.960403	Binding	0.406	0.734	0.875											-5.880	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-5.06	Deleterious	0.985	Probably Damaging	0.721	Possibly Damaging	3.50	Benign	0.00	Affected			0.0861	0.5491		-2	-3	8.0	-0.94
c.423C>G	I141M 2D AIThe SynGAP1 I141M 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 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are mixed, with an equal split between benign and pathogenic calls and no definitive evidence from Foldetta. Thus, the variant is most likely benign based on the current computational evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.577021	Binding	0.367	0.877	0.500											-7.437	In-Between	0.962	Likely Pathogenic	Likely Pathogenic										0.112	Likely Benign	-1.54	Neutral	0.567	Possibly Damaging	0.332	Benign	3.57	Benign	0.01	Affected			0.0664	0.2661		2	1	-2.6	18.03
c.559C>G	L187V 2D AIThe SynGAP1 missense variant L187V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors lean toward a benign classification, but the single high‑accuracy tool indicates pathogenicity. Thus, the variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-10.543	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.136	Likely Benign	-2.24	Neutral	0.437	Benign	0.079	Benign	3.81	Benign	0.02	Affected			0.1525	0.3509		2	1	0.4	-14.03
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	-2.50	Deleterious	0.118	Benign	0.037	Benign	4.09	Benign	0.02	Affected			0.1824	0.5890		0	1	-0.4	-0.94
c.695C>T	A232V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A232V is catalogued in gnomAD (ID 6‑33435546‑C‑T) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic calls are reported by REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, and the Foldetta stability assessment predicts benign. premPS is inconclusive and therefore not considered. Overall, the majority of independent predictors lean toward pathogenicity, but the stability‑based Foldetta suggests a benign effect. With no ClinVar classification to contradict, the variant is most likely pathogenic according to the prevailing computational evidence. 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								6-33435546-C-T	2	1.24e-6	-9.418	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.1	0.23	Likely Benign	0.32	Likely Benign	0.55	Ambiguous	0.539	Likely Pathogenic	-2.99	Deleterious	0.608	Possibly Damaging	0.240	Benign	5.85	Benign	0.06	Tolerated	3.40	14	0.1202	0.6027		0	0	2.4	28.05
c.786T>A	N262K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N262K has no ClinVar entry and is not present in gnomAD. Prediction tools that indicate a benign effect include FoldX, premPS, and FATHMM. Those that predict a pathogenic effect comprise REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are reported by Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic impact for N262K. 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	C2	0.284882	Structured	0.399879	Uncertain	0.912	0.240	0.000											-12.512	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.47	Likely Benign	0.2	1.00	Ambiguous	0.74	Ambiguous	0.33	Likely Benign	0.531	Likely Pathogenic	-5.13	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	5.84	Benign	0.02	Affected			0.1799	0.3413		1	0	-0.4	14.07
c.786T>G	N262K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N262K has no ClinVar entry and is not reported in gnomAD. Functional prediction tools largely disagree: benign predictions come from FoldX, premPS, and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by Rosetta and Foldetta. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as inconclusive. Taken together, the majority of evidence points to a pathogenic effect for N262K. This conclusion is consistent with the absence of a ClinVar classification, as there is no existing report to contradict the prediction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.284882	Structured	0.399879	Uncertain	0.912	0.240	0.000											-12.512	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.47	Likely Benign	0.2	1.00	Ambiguous	0.74	Ambiguous	0.33	Likely Benign	0.532	Likely Pathogenic	-5.13	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	5.84	Benign	0.02	Affected			0.1799	0.3413		1	0	-0.4	14.07
c.952C>A	P318T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318T is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly favor a deleterious effect: REVEL, FoldX, 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 pathogenic or likely pathogenic. No tool in the dataset predicts a benign outcome; the only inconclusive results come from Rosetta, Foldetta, and premPS, which are treated as unavailable evidence. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is uncertain. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000											-10.759	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.03	Destabilizing	0.2	1.54	Ambiguous	1.79	Ambiguous	0.84	Ambiguous	0.680	Likely Pathogenic	-7.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.84	Pathogenic	0.01	Affected			0.1583	0.6044		0	-1	0.9	3.99
c.1036G>A	V346M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V346M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FoldX, whereas the majority of other in silico methods (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, PROVEAN, AlphaMissense‑Optimized, and the SGM‑Consensus score) indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains uncertain. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-10.218	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.1	2.52	Destabilizing	1.41	Ambiguous	0.67	Ambiguous	0.367	Likely Benign	-2.72	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.05	Affected			0.1050	0.4749		2	1	-2.3	32.06
c.1267T>A	Y423N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423N is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include SIFT and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-10.937	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.1	4.08	Destabilizing	4.03	Destabilizing	2.07	Destabilizing	0.501	Likely Pathogenic	-7.47	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.06	Tolerated			0.1405	0.0412		-2	-2	-2.2	-49.07
c.1273A>C	T425P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as deleterious, while only FATHMM predicts a benign outcome; premPS is uncertain. High‑accuracy tools reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a pathogenic effect. Taken together, the overwhelming majority of evidence supports a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-12.318	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.81	Destabilizing	0.3	6.49	Destabilizing	4.65	Destabilizing	0.77	Ambiguous	0.512	Likely Pathogenic	-5.16	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.03	Affected			0.1815	0.3469		0	-1	-0.9	-3.99
c.1355T>C	V452A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V452A 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 SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta remains inconclusive. Overall, the consensus of the available tools points to a pathogenic effect for V452A, and 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	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000											-10.423	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.21	Destabilizing	0.0	1.51	Ambiguous	1.86	Ambiguous	2.18	Destabilizing	0.505	Likely Pathogenic	-3.95	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.21	Benign	0.00	Affected			0.2642	0.2521		0	0	-2.4	-28.05
c.1462A>G	T488A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T488A is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the majority of tools (FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) predict pathogenicity; Rosetta and premPS are uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence indicates that T488A is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125											-11.341	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.12	Destabilizing	0.2	1.99	Ambiguous	2.06	Destabilizing	0.57	Ambiguous	0.497	Likely Benign	-4.64	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.24	Benign	0.01	Affected			0.2871	0.2872		1	0	2.5	-30.03
c.1541T>C	I514T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I514T has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of algorithms—SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. Rosetta reports an uncertain outcome and is not included in the consensus groups. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. Taken together, the evidence overwhelmingly points to a pathogenic effect, and this conclusion is not contradicted by the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.049374	Structured	0.221408	Uncertain	0.948	0.266	0.000											-8.820	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	2.92	Destabilizing	0.1	1.88	Ambiguous	2.40	Destabilizing	1.94	Destabilizing	0.617	Likely Pathogenic	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.82	Benign	0.00	Affected			0.0962	0.0480		0	-1	-5.2	-12.05
c.1999A>T	I667F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I667F missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign calls are limited to FATHMM, while the remaining 11 predictors—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—classify the change as pathogenic. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports a pathogenic effect. No prediction is inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.142424	Structured	0.083597	Uncertain	0.927	0.379	0.000											-14.389	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	7.55	Destabilizing	0.3	1.80	Ambiguous	4.68	Destabilizing	0.86	Ambiguous	0.569	Likely Pathogenic	-3.98	Deleterious	0.998	Probably Damaging	0.790	Possibly Damaging	2.96	Benign	0.00	Affected			0.0668	0.2648		1	0	-1.7	34.02
c.2012A>T	D671V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the majority of predictions (seven pathogenic vs. three benign) support a pathogenic classification. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-12.376	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.1	0.51	Ambiguous	0.57	Ambiguous	0.14	Likely Benign	0.379	Likely Benign	-6.08	Deleterious	0.975	Probably Damaging	0.885	Possibly Damaging	3.31	Benign	0.01	Affected			0.0820	0.6651		-2	-3	7.7	-15.96
c.2036T>C	F679S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679S is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining 12 tools (SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the variant as pathogenic. FoldX reports an uncertain outcome and is therefore not counted as evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the preponderance of pathogenic predictions and the absence of any benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000											-12.159	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	1.86	Ambiguous	0.4	2.20	Destabilizing	2.03	Destabilizing	1.28	Destabilizing	0.575	Likely Pathogenic	-7.86	Deleterious	0.998	Probably Damaging	0.986	Probably Damaging	3.50	Benign	0.04	Affected			0.4276	0.0200		-3	-2	-3.6	-60.10
c.2092G>A	E698K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E698K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a benign impact. Because the high‑accuracy predictions are split, the overall evidence is inconclusive, but the majority of tools lean toward pathogenicity. The variant is therefore most likely pathogenic based on the preponderance of predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.120615	Structured	0.417514	Uncertain	0.922	0.315	0.000											-8.881	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.23	Likely Benign	0.1	0.38	Likely Benign	0.31	Likely Benign	-0.07	Likely Benign	0.466	Likely Benign	-3.79	Deleterious	0.991	Probably Damaging	0.951	Probably Damaging	3.37	Benign	0.01	Affected			0.2218	0.4383		0	1	-0.4	-0.94
c.2134G>C	G712R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G712R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors—PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, Rosetta, and the SGM Consensus—classify it as pathogenic. Two tools, FoldX and premPS, return uncertain results. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta each predict a deleterious effect. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000											-11.776	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	1.75	Ambiguous	0.0	4.68	Destabilizing	3.22	Destabilizing	0.82	Ambiguous	0.458	Likely Benign	-6.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.01	Affected			0.1229	0.4482		-3	-2	-4.1	99.14
c.2458T>G	Y820D 2D AIThe SynGAP1 missense variant Y820D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools suggests that Y820D is most likely pathogenic, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-10.497	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.169	Likely Benign	-2.77	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.73	Benign	0.08	Tolerated			0.4113	0.0704		-4	-3	-2.2	-48.09
c.2719A>C	S907R 2D AIThe SynGAP1 missense variant S907R 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 the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (a majority vote of the same four high‑accuracy tools) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250											-3.852	Likely Benign	0.963	Likely Pathogenic	Likely Pathogenic										0.082	Likely Benign	-0.71	Neutral	0.998	Probably Damaging	0.951	Probably Damaging	2.73	Benign	0.34	Tolerated			0.0964	0.3441		0	-1	-3.7	69.11
c.2721C>A	S907R 2D AIThe SynGAP1 missense variant S907R has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. AlphaMissense‑Optimized also classifies the variant as pathogenic, whereas the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as benign; Foldetta results are unavailable. Overall, the majority of tools (five benign vs. four pathogenic) lean toward a benign interpretation, and there is no ClinVar evidence contradicting this assessment. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250											-3.852	Likely Benign	0.963	Likely Pathogenic	Likely Pathogenic										0.089	Likely Benign	-0.71	Neutral	0.998	Probably Damaging	0.951	Probably Damaging	2.73	Benign	0.34	Tolerated			0.0964	0.3441		0	-1	-3.7	69.11
c.2721C>G	S907R 2D AIThe SynGAP1 missense variant S907R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the predictions are mixed but lean toward a benign interpretation, with no conflict with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250											-3.852	Likely Benign	0.963	Likely Pathogenic	Likely Pathogenic										0.089	Likely Benign	-0.71	Neutral	0.998	Probably Damaging	0.951	Probably Damaging	2.73	Benign	0.34	Tolerated			0.0964	0.3441		0	-1	-3.7	69.11
c.2788C>G	P930A 2D AIThe SynGAP1 missense variant P930A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P930A is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-8.938	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.392	Likely Benign	-6.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.3376	0.4983		1	-1	3.4	-26.04
c.3270T>A	N1090K 2D AIThe SynGAP1 missense variant N1090K is reported in ClinVar as “None” and is present in gnomAD (ID 6‑33443822‑T‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) and the consensus result lean toward a benign interpretation. This conclusion does not contradict ClinVar, which currently has no pathogenic classification 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								6-33443822-T-A	2	1.28e-6	-3.423	Likely Benign	0.963	Likely Pathogenic	Likely Pathogenic										0.053	Likely Benign	-1.52	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.73	Benign	0.18	Tolerated	3.77	5	0.2147	0.6121		0	1	-0.4	14.07
c.3270T>G	N1090K 2D AIThe SynGAP1 missense variant N1090K has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. The overall balance of evidence leans toward a benign interpretation, and this is consistent with the lack of a ClinVar 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		0.896620	Disordered	0.979886	Binding	0.341	0.887	1.000											-3.423	Likely Benign	0.963	Likely Pathogenic	Likely Pathogenic										0.053	Likely Benign	-1.52	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.73	Benign	0.18	Tolerated	3.77	5	0.2147	0.6121		0	1	-0.4	14.07
c.416G>T	S139I 2D AIThe SynGAP1 missense variant S139I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; pathogenic predictions come from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.600637	Binding	0.353	0.900	0.250											-9.228	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.203	Likely Benign	-3.36	Deleterious	0.380	Benign	0.102	Benign	4.09	Benign	0.03	Affected			0.0948	0.4796		-1	-2	5.3	26.08
c.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	-3.77	Deleterious	0.535	Possibly Damaging	0.310	Benign	3.92	Benign	0.00	Affected			0.1891	0.5038		0	-1	0.9	3.99
c.1043T>G	V348G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V348G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among pathogenic predictions and the lack of a benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.170161	Structured	0.346556	Uncertain	0.951	0.414	0.000											-12.793	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	3.97	Destabilizing	0.2	5.70	Destabilizing	4.84	Destabilizing	2.23	Destabilizing	0.419	Likely Benign	-6.18	Deleterious	0.637	Possibly Damaging	0.989	Probably Damaging	1.56	Pathogenic	0.00	Affected			0.2229	0.2082		-1	-3	-4.6	-42.08
c.1072T>C	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.290	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1074C>A	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1074C>G	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the majority of reliable tools predict a pathogenic impact for F358L. This conclusion does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1459A>G	N487D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N487D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include Rosetta, Foldetta, and FATHMM, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and premPS are inconclusive. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, while Foldetta indicates a benign folding stability change. Overall, the preponderance of evidence points to a pathogenic effect for this variant, 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	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-13.330	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	0.80	Ambiguous	0.2	-0.21	Likely Benign	0.30	Likely Benign	0.84	Ambiguous	0.513	Likely Pathogenic	-4.97	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.81	Benign	0.01	Affected			0.1728	0.1815		2	1	0.0	0.98
c.1864A>C	T622P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T622P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic. No tool predicts a benign outcome; the only inconclusive result is premPS, which is listed as uncertain. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) also indicates pathogenic. Consequently, 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	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-16.410	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	2.81	Destabilizing	0.4	8.90	Destabilizing	5.86	Destabilizing	0.78	Ambiguous	0.924	Likely Pathogenic	-5.57	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.57	Pathogenic	0.01	Affected			0.1700	0.3876		0	-1	-0.9	-3.99
c.191T>A	I64K 2D AIThe SynGAP1 missense variant I64K is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this conclusion does not contradict the ClinVar status, which contains no report for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.475481	Uncertain	0.478	0.747	0.125											-3.206	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.159	Likely Benign	-0.47	Neutral	0.334	Benign	0.029	Benign	4.07	Benign	0.00	Affected			0.0878	0.0740		-2	-3	-8.4	15.01
c.2011G>T	D671Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D671Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized and the SGM‑Consensus both indicate pathogenicity, while Foldetta predicts a benign effect on protein stability. Because the majority of standard predictors lean toward pathogenicity and the two high‑confidence tools also favor a deleterious outcome, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000											-13.107	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.05	Likely Benign	0.18	Likely Benign	0.11	Likely Benign	0.385	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.961	Probably Damaging	3.29	Benign	0.00	Affected			0.0564	0.6376		-4	-3	2.2	48.09
c.324G>C	K108N 2D AISynGAP1 missense variant K108N is reported in gnomAD (6‑33432189‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); pathogenic calls from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign; Foldetta results are unavailable. Consequently, the evidence is evenly split, with no single prediction dominating. The variant is therefore not clearly benign or pathogenic based on current computational data, and this lack of consensus does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875								6-33432189-G-C	1	6.20e-7	-3.015	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.068	Likely Benign	-1.35	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.07	Benign	0.03	Affected	3.61	5	0.3904	0.1820		0	1	0.4	-14.07
c.324G>T	K108N 2D AIThe SynGAP1 missense variant K108N is not reported in ClinVar and has no gnomAD entry. Consensus predictions from multiple in‑silico tools are split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which labels the variant as Likely Benign. Pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized, the latter two high‑accuracy predictors both flagging the variant as Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not return a result for this variant, so its stability impact is unavailable. Overall, the majority of high‑confidence tools (AlphaMissense‑Optimized and the SGM‑Consensus) disagree, with AlphaMissense‑Optimized indicating pathogenicity while the consensus suggests benign. Because ClinVar contains no classification, there is no contradiction; the variant is most likely pathogenic based on the most reliable predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.015	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.068	Likely Benign	-1.35	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.07	Benign	0.03	Affected	3.61	5	0.3904	0.1820		0	1	0.4	-14.07
c.3467C>G	A1156G 2D AIThe SynGAP1 missense variant A1156G is not reported in ClinVar and has no allele in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the change as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also reports a likely pathogenic outcome. Foldetta results are unavailable for this variant. Overall, the consensus of the available predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500											-3.728	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.230	Likely Benign	-3.02	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.62	Pathogenic	0.00	Affected			0.2214	0.4461		1	0	-2.2	-14.03
c.3472G>C	V1158L 2D AIThe SynGAP1 missense variant V1158L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Benign; Foldetta results are unavailable. Overall, the majority of evidence (five benign versus four pathogenic predictions, plus a benign consensus) points to a benign classification, and this does not contradict any ClinVar status because no ClinVar claim exists. Thus, the variant is most likely benign, though the AlphaMissense‑Optimized prediction introduces some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.877504	Binding	0.369	0.847	0.250											-2.345	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.187	Likely Benign	-0.73	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.78	Benign	0.56	Tolerated			0.1066	0.4642		2	1	-0.4	14.03
c.3541A>G	K1181E 2D AIThe SynGAP1 missense variant K1181E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense (Default and Optimized) 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 pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-3.244	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-1.19	Neutral	0.995	Probably Damaging	0.949	Probably Damaging	2.86	Benign	0.55	Tolerated			0.2862	0.0877		0	1	0.4	0.94
c.575C>T	A192V 2D AIThe SynGAP1 missense variant A192V is not 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, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b remains uncertain. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic majority (2 pathogenic vs. 1 benign, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that A192V 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.			0.422041	Structured	0.428195	Uncertain	0.321	0.589	0.125											-7.464	In-Between	0.964	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-2.66	Deleterious	0.996	Probably Damaging	0.877	Possibly Damaging	4.01	Benign	0.11	Tolerated			0.0904	0.5066		0	0	2.4	28.05
c.662A>C	E221A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E221A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the predictions are split, but the two high‑confidence pathogenic calls outweigh the single high‑confidence benign call, suggesting the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.413334	Uncertain	0.891	0.283	0.000											-12.906	Likely Pathogenic	0.964	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.0	-0.11	Likely Benign	0.10	Likely Benign	0.52	Ambiguous	0.796	Likely Pathogenic	-4.70	Deleterious	0.231	Benign	0.081	Benign	5.82	Benign	0.01	Affected			0.3486	0.7335		0	-1	5.3	-58.04
c.1066C>A	R356S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R356S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and SIFT, whereas the remaining tools—premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is inconclusive. Taken together, the preponderance of evidence points to a pathogenic effect for R356S, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.219301	Structured	0.395028	Uncertain	0.802	0.373	0.250											-13.059	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	0.79	Ambiguous	0.90	Ambiguous	1.04	Destabilizing	0.292	Likely Benign	-5.28	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	1.84	Pathogenic	0.07	Tolerated			0.2891	0.4491		0	-1	3.7	-69.11
c.1325A>T	K442I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K442I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy assessments are: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of predictions, including the two high‑accuracy pathogenic calls, indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-14.921	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.16	Likely Benign	0.1	-0.16	Likely Benign	0.00	Likely Benign	0.30	Likely Benign	0.350	Likely Benign	-6.91	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.37	Benign	0.02	Affected			0.0943	0.3073		-2	-3	8.4	-15.01
c.1465C>T	L489F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489F is listed in ClinVar with an uncertain significance (ClinVar ID 522018.0) and is present in the gnomAD database (gnomAD ID 6‑33438497‑C‑T). In silico prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome, while no tool predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No prediction or folding‑stability result is missing or ambiguous. **Thus, the variant is most likely pathogenic based on the collective predictions, 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	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125					Uncertain		2	6-33438497-C-T	1	6.20e-7	-12.066	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	1.72	Ambiguous	0.5	1.14	Ambiguous	1.43	Ambiguous	0.56	Ambiguous	0.724	Likely Pathogenic	-3.76	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.51	Pathogenic	0.01	Affected	3.37	35	0.0791	0.3729		2	0	-1.0	34.02	246.4	-17.8	0.0	0.0	0.6	0.1						X		Potentially Benign	The iso-butyl side chain of Leu489, located in the α-helix (res. Leu489-Glu519) within an inter-helix space of four helices (res. Ala461-Phe476, res. Val441-Ser457, and res. Met414-Glu436), packs with hydrophobic residues (e.g., Cys432, Ala448, Lys444, Ala493, Val447, Met468) in the inter-helix space. In the variant simulations, the phenyl ring of the Phe489 side chain can also pack favorably in the hydrophobic region. However, due to the size difference, the aromatic side chain of Phe489 tends to reposition to escape the tight region to accommodate the larger side chain, stacking with Lys444. Although no apparent negative changes are observed during the variant simulation, the size difference between the swapped residues could affect the protein folding process.
c.1619A>T	Q540L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540L has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from Rosetta, Foldetta, premPS, and SIFT, while pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX is uncertain and therefore not considered. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for Q540L, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000											-14.266	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	-0.71	Ambiguous	0.1	0.44	Likely Benign	-0.14	Likely Benign	0.50	Likely Benign	0.756	Likely Pathogenic	-6.96	Deleterious	0.994	Probably Damaging	0.977	Probably Damaging	-1.06	Pathogenic	0.08	Tolerated			0.0654	0.3601		-2	-2	7.3	-14.97
c.1654T>G	C552G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552G is not reported in ClinVar and is absent from gnomAD. In silico predictors that classify the change as benign include FoldX, Rosetta, Foldetta, and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy subset shows AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With six pathogenic versus four benign predictions overall, the evidence leans toward a deleterious effect. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000											-11.570	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.0	0.29	Likely Benign	0.28	Likely Benign	1.06	Destabilizing	0.745	Likely Pathogenic	-10.20	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.21	Pathogenic	0.35	Tolerated			0.2338	0.1930		-3	-3	-2.9	-46.09
c.1700A>T	E567V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E567V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Rosetta alone is inconclusive and treated as unavailable. Overall, the majority of evidence points to a pathogenic effect for E567V, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-15.638	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.27	Likely Benign	0.1	0.59	Ambiguous	0.43	Likely Benign	0.38	Likely Benign	0.440	Likely Benign	-6.77	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	3.48	Benign	0.06	Tolerated			0.0573	0.6175		-2	-2	7.7	-29.98
c.1739G>A	G580D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580D is not reported in ClinVar and has no entries in gnomAD. Consensus from multiple in silico predictors indicates a pathogenic effect: SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic, while premPS and Rosetta are uncertain. High‑accuracy tools reinforce this assessment: 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. No benign predictions are present. 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	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-10.086	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.1	1.39	Ambiguous	2.12	Destabilizing	0.83	Ambiguous	0.712	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.25	Pathogenic	0.04	Affected			0.1793	0.1971		1	-1	-3.1	58.04
c.1811C>T	S604L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S604L is listed in ClinVar with an “Uncertain” status (ClinVar ID 1055027.0) and is present in gnomAD (ID 6‑33440863‑C‑T). Prediction tools that agree on a benign effect are premPS and FATHMM. Tools that predict a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, 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, 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	0.010926	Structured	0.192527	Uncertain	0.911	0.195	0.000					Uncertain		1	6-33440863-C-T	6	3.72e-6	-14.683	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	-0.94	Ambiguous	0.1	-1.24	Ambiguous	-1.09	Ambiguous	-0.31	Likely Benign	0.639	Likely Pathogenic	-5.97	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	3.09	Benign	0.00	Affected	3.37	35	0.1177	0.4518		-3	-2	4.6	26.08	234.0	-49.6	0.0	0.1	0.3	0.5	X			X				Potentially Pathogenic	Ser604 is located in a short turn between an α helix (res. Glu582-Met603) and a short α helical section (res. Ser606-Phe608). In the WT simulations, the hydroxyl side chain of Ser604 periodically hydrogen bonds with the backbone carbonyl groups of other α helix residues (e.g., Pro600, Met603). Serine weakens the α helix secondary structure, and thus, Ser604 along with Pro605 breaks the α helix, facilitating the turn in the WT structure.In contrast, in the variant simulations, Leu604 forms a few hydrophobic interactions (e.g., Leu607, Phe608). More importantly, the helix end is more stable than with Ser604 in the WT. The residue swap could have a more profound effect on the actual folding process, for example, by preventing the bending at the α helix end, than what the simulations suggest.Moreover, Ser604 directly hydrogen bonds with Ras residues Ser65 and Ala66 in the WT SynGAP-Ras complex. The hydrophobic leucine cannot maintain these interactions with Ras at the GAP-Ras interface. Thus, the effect of the residue swap on the complex formation with the GTPase cannot be fully explored in the solvent-only simulations.
c.1915T>G	F639V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F639V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: FATHMM is the sole benign predictor, while the remaining 12 tools (SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity; Rosetta is uncertain and is therefore not counted. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-12.910	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	4.17	Destabilizing	0.1	1.18	Ambiguous	2.68	Destabilizing	1.47	Destabilizing	0.560	Likely Pathogenic	-6.97	Deleterious	0.992	Probably Damaging	0.756	Possibly Damaging	3.08	Benign	0.02	Affected			0.2074	0.1583		-1	-1	1.4	-48.04
c.256G>C	V86L 2D AIThe SynGAP1 missense variant V86L is reported in ClinVar as “not listed” and is present in the gnomAD database (ID 6‑33425864‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.685117	Disordered	0.552911	Binding	0.295	0.887	0.500								6-33425864-G-C	1	6.20e-7	-3.658	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.081	Likely Benign	-0.84	Neutral	0.267	Benign	0.097	Benign	3.85	Benign	0.00	Affected	4.32	1	0.1121	0.5386		1	2	-0.4	14.03
c.2771C>G	P924R 2D AIThe SynGAP1 missense variant P924R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL and ESM1b, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. Grouping by consensus, the pathogenic group outweighs the benign group. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta data are unavailable. Overall, the preponderance of evidence indicates that P924R is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.024	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.420	Likely Benign	-6.20	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1314	0.2083		0	-2	-2.9	59.07
c.2957A>T	E986V 2D AIThe SynGAP1 E986V missense variant is not reported in ClinVar and has no gnomAD entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b, whereas pathogenic predictions arise from PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (pathogenic), and PROVEAN (pathogenic)—also indicates pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a pathogenic effect for E986V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750											-4.511	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-3.48	Deleterious	0.018	Benign	0.028	Benign	2.10	Pathogenic	0.00	Affected			0.1146	0.7960		-2	-2	7.7	-29.98
c.319A>T	R107W 2D AIThe SynGAP1 missense variant R107W is not 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 predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs two benign), and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs three benign) points to a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.663448	Binding	0.331	0.863	0.875											-4.963	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic										0.328	Likely Benign	-2.99	Deleterious	0.983	Probably Damaging	0.624	Possibly Damaging	2.95	Benign	0.00	Affected			0.1146	0.4228		2	-3	3.6	30.03
c.3603G>C	E1201D 2D AIThe SynGAP1 missense variant E1201D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, and SIFT, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-8.727	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.150	Likely Benign	-1.55	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.51	Tolerated			0.1341	0.3335		3	2	0.0	-14.03
c.3603G>T	E1201D 2D AIThe SynGAP1 missense variant E1201D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, and SIFT, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-8.727	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.150	Likely Benign	-1.55	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.51	Tolerated			0.1341	0.3335		3	2	0.0	-14.03
c.3786C>G	I1262M 2D AIThe SynGAP1 missense variant I1262M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also leans pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.707863	Binding	0.886	0.576	0.125											-9.081	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.248	Likely Benign	-2.49	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.00	Affected			0.0671	0.2726		2	1	-2.6	18.03
c.398T>G	L133R 2D AIThe SynGAP1 missense variant L133R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome (3 pathogenic vs. 1 benign votes). AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a pathogenic classification for L133R, and this assessment does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-8.857	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic										0.389	Likely Benign	-2.57	Deleterious	0.002	Benign	0.005	Benign	3.55	Benign	0.00	Affected			0.1522	0.0479		-3	-2	-8.3	43.03
c.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	-3.96	Deleterious	0.966	Probably Damaging	0.599	Possibly Damaging	3.86	Benign	0.00	Affected			0.1967	0.3989		0	-2	2.9	-59.07
c.683C>G	T228R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T228R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-7.218	In-Between	0.965	Likely Pathogenic	Likely Pathogenic	-0.23	Likely Benign	0.1	0.69	Ambiguous	0.23	Likely Benign	0.67	Ambiguous	0.693	Likely Pathogenic	-3.40	Deleterious	0.952	Possibly Damaging	0.694	Possibly Damaging	5.60	Benign	0.01	Affected			0.1108	0.3405		-1	-1	-3.8	55.08
c.986G>C	R329P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R329P is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of algorithms predict a pathogenic outcome: FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic,” and premPS is uncertain. 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) predicts pathogenicity. Overall, the evidence overwhelmingly points to a pathogenic effect for R329P, 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	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-14.528	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.2	4.99	Destabilizing	4.03	Destabilizing	0.73	Ambiguous	0.350	Likely Benign	-4.28	Deleterious	0.902	Possibly Damaging	0.544	Possibly Damaging	4.00	Benign	0.01	Affected			0.2215	0.4099		0	-2	2.9	-59.07
c.1307A>G	E436G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the majority of algorithms (SGM‑Consensus, REVEL, Rosetta, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, premPS, and Foldetta are inconclusive. 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’s stability prediction is uncertain. 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 annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.355	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.1	2.02	Destabilizing	1.76	Ambiguous	0.58	Ambiguous	0.802	Likely Pathogenic	-6.63	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	4.61	Benign	0.03	Affected			0.2910	0.4841		0	-2	3.1	-72.06
c.1417G>C	V473L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and Foldetta, while those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of tools (seven pathogenic vs. six benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion is not contradicted by the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000											-9.073	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	-0.29	Likely Benign	0.1	-0.52	Ambiguous	-0.41	Likely Benign	0.35	Likely Benign	0.336	Likely Benign	-2.85	Deleterious	0.929	Possibly Damaging	0.917	Probably Damaging	3.43	Benign	0.21	Tolerated			0.0708	0.3921		2	1	-0.4	14.03
c.1417G>T	V473L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473L is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and Foldetta, while those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of tools (seven pathogenic vs. six benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion is not contradicted by the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000											-9.073	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	-0.29	Likely Benign	0.1	-0.52	Ambiguous	-0.41	Likely Benign	0.35	Likely Benign	0.335	Likely Benign	-2.85	Deleterious	0.929	Possibly Damaging	0.917	Probably Damaging	3.43	Benign	0.21	Tolerated			0.0708	0.3921		2	1	-0.4	14.03
c.1591T>C	C531R 2D AIThe SynGAP1 missense variant C531R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and polyPhen‑2 HumVar, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, 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 from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar classification because the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-12.600	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	2.0	-0.27	Likely Benign	0.02	Likely Benign	1.40	Destabilizing	0.619	Likely Pathogenic	-9.85	Deleterious	0.929	Possibly Damaging	0.385	Benign	-1.24	Pathogenic	0.00	Affected			0.1322	0.1566		-4	-3	-7.0	53.05
c.2042G>A	G681D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas the remaining 11 tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score all predict pathogenicity. The high‑accuracy methods reinforce this view: AlphaMissense‑Optimized returns a pathogenic classification; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts a pathogenic effect. premPS is inconclusive and is treated as unavailable. Taken together, the overwhelming majority of evidence points to a pathogenic impact for G681D. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000											-12.451	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	2.62	Destabilizing	1.5	4.54	Destabilizing	3.58	Destabilizing	0.96	Ambiguous	0.471	Likely Benign	-6.98	Deleterious	0.999	Probably Damaging	0.840	Possibly Damaging	3.45	Benign	0.00	Affected			0.1697	0.1695		1	-1	-3.1	58.04
c.2773C>T	L925F 2D AIThe SynGAP1 missense variant L925F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the preponderance of computational evidence points to a pathogenic impact for the L925F substitution, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-4.147	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.242	Likely Benign	-3.04	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.32	Pathogenic	0.00	Affected			0.0897	0.2881		2	0	-1.0	34.02
c.3454G>A	E1152K 2D AIThe SynGAP1 missense variant E1152K is reported in gnomAD (ID 6‑33444489‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts a deleterious effect, and the SGM‑Consensus confirms a likely pathogenic outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective evidence points to a pathogenic effect, and this conclusion is not contradicted by ClinVar, which contains no classification for E1152K. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500								6-33444489-G-A	1	6.20e-7	-3.612	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-2.64	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.38	Pathogenic	0.02	Affected	3.77	5	0.2942	0.6397		1	0	-0.4	-0.94
c.3545A>T	E1182V 2D AIThe SynGAP1 missense variant E1182V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the preponderance of evidence (seven pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.530232	Binding	0.597	0.651	0.375											-4.966	Likely Benign	0.966	Likely Pathogenic	Likely Pathogenic										0.124	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.59	Benign	0.00	Affected			0.0447	0.6364		-2	-2	7.7	-29.98
c.3668T>G	L1223R 2D AIThe SynGAP1 missense variant L1223R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as likely pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of computational evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-15.396	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic										0.317	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.986	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1078	0.0919		-3	-2	-8.3	43.03
c.623C>G	P208R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM. The majority of other in silico predictors (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact, while Rosetta remains 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 any benign consensus, the variant is most likely pathogenic, with no contradiction to ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-11.929	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	5.25	Destabilizing	1.6	1.39	Ambiguous	3.32	Destabilizing	1.16	Destabilizing	0.472	Likely Benign	-7.50	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	0.00	Affected			0.1676	0.3118		0	-2	-2.9	59.07
c.776G>A	R259Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R259Q is catalogued in gnomAD (6‑33437681‑G‑A) but has no entry in ClinVar. In silico assessment shows a consensus of pathogenicity: 9 of 11 evaluated tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a deleterious effect, while only FATHMM indicates a benign outcome. Predictions of protein‑stability change are inconclusive, with FoldX, Rosetta and the combined Foldetta method returning uncertain results. High‑accuracy predictors reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies the variant as likely pathogenic; Foldetta remains uncertain. Overall, the computational evidence strongly favors a pathogenic interpretation, and this is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.338208	Uncertain	0.885	0.255	0.250								6-33437681-G-A	1	6.20e-7	-12.598	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	1.19	Ambiguous	0.3	1.30	Ambiguous	1.25	Ambiguous	1.40	Destabilizing	0.851	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.978	Probably Damaging	5.81	Benign	0.01	Affected	3.39	15	0.3329	0.2703		1	1	1.0	-28.06	258.7	52.8	0.1	0.1	-0.3	0.4	X	X						Potentially Pathogenic	The guanidinium group of Arg259, located at the beginning of an anti-parallel β sheet strand (res. Arg259-Arg272), forms salt bridges with the carboxylate groups of Asp684 at the end of an α helix (res. Ile683-Gln702, GAP domain) and Asp261 on the same β strand. The Arg259 side chain also frequently forms hydrogen bonds with the backbone carbonyl groups of Ser257, Asn256, and Asp255. In the variant simulations, the carboxamide group of the Gln259 side chain cannot form salt bridges or maintain hydrogen bonding with the carboxylate group of Asp684, which could affect the tertiary structure assembly between the C2 and GAP domains. Notably, the amino group of the Lys254 side chain maintains a salt bridge with Asp684 and Glu244 throughout the variant simulations, but this interaction is not maintained in the WT simulations. Thus, the partially or loosely α helical conformation of a lysine-containing loop (res. Lys251-Ser257), which extends to a nearby α helix (res. Met414-Asn426), could be stabilized due to the residue swap.
c.994G>T	D332Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D332Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and premPS, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus confirms a likely pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Overall, the majority of evidence points to a pathogenic impact for D332Y, 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	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-14.210	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.6	-0.07	Likely Benign	0.54	Ambiguous	0.41	Likely Benign	0.485	Likely Benign	-7.33	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.20	Pathogenic	0.00	Affected			0.0372	0.4018		-4	-3	2.2	48.09
c.1379A>C	K460T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K460T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) yield uncertain or inconclusive results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus majority vote (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD/Rosetta analysis remains inconclusive. Overall, the majority of evidence points to a pathogenic impact for K460T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.187	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.1	1.16	Ambiguous	1.20	Ambiguous	0.77	Ambiguous	0.208	Likely Benign	-5.02	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.35	Benign	0.07	Tolerated			0.1858	0.3848		0	-1	3.2	-27.07
c.1384A>G	K462E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta is uncertain. Overall, the majority of predictions (7 pathogenic vs. 5 benign) and the high‑accuracy tools support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-14.696	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.34	Likely Benign	0.0	1.56	Ambiguous	0.95	Ambiguous	0.33	Likely Benign	0.433	Likely Benign	-3.88	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.49	Benign	0.15	Tolerated			0.4145	0.1022		0	1	0.4	0.94
c.1459A>T	N487Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N487Y has no ClinVar entry and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and FATHMM, whereas the majority of algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for N487Y, 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	0.209395	Structured	0.338511	Uncertain	0.890	0.243	0.125											-14.921	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	1.15	Ambiguous	0.0	-0.05	Likely Benign	0.55	Ambiguous	0.33	Likely Benign	0.652	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.00	Affected			0.0587	0.2946		-2	-2	2.2	49.07
c.1748A>C	D583A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D583A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Rosetta, Foldetta, premPS, SIFT, and ESM1b, while those that agree on a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain and thus not counted. High‑accuracy methods give AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (10 pathogenic vs. 5 benign) and the two high‑accuracy pathogenic calls outweigh the single high‑accuracy benign call, indicating that the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-4.545	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.2	-0.16	Likely Benign	0.41	Likely Benign	0.13	Likely Benign	0.787	Likely Pathogenic	-7.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.39	Pathogenic	0.14	Tolerated			0.3025	0.3705		0	-2	5.3	-44.01
c.1905C>A	N635K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N635K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for N635K, 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	0.039760	Structured	0.060246	Uncertain	0.900	0.252	0.000											-13.144	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.60	Ambiguous	0.1	0.75	Ambiguous	0.68	Ambiguous	0.85	Ambiguous	0.332	Likely Benign	-5.64	Deleterious	0.949	Possibly Damaging	0.550	Possibly Damaging	2.92	Benign	0.00	Affected			0.2125	0.2510		1	0	-0.4	14.07
c.1905C>G	N635K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N635K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM Consensus as Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. Overall, the preponderance of evidence from multiple in silico predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.039760	Structured	0.060246	Uncertain	0.900	0.252	0.000											-13.144	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.60	Ambiguous	0.1	0.75	Ambiguous	0.68	Ambiguous	0.85	Ambiguous	0.332	Likely Benign	-5.64	Deleterious	0.949	Possibly Damaging	0.550	Possibly Damaging	2.92	Benign	0.00	Affected			0.2125	0.2510		1	0	-0.4	14.07
c.194A>G	H65R 2D AIThe SynGAP1 missense variant H65R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33425802‑A‑G). 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.476188	Uncertain	0.458	0.758	0.125					Uncertain		1	6-33425802-A-G	1	6.20e-7	-1.980	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.073	Likely Benign	-1.60	Neutral	0.462	Possibly Damaging	0.227	Benign	4.19	Benign	0.00	Affected	4.32	1	0.1483	0.1671		2	0	-1.3	19.05
c.2785A>C	N929H 2D AIThe SynGAP1 missense variant N929H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain, and Foldetta results are unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. With no conflicting ClinVar annotation, the collective evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-7.070	In-Between	0.967	Likely Pathogenic	Likely Pathogenic										0.342	Likely Benign	-3.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.1507	0.7659		2	1	0.3	23.04
c.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	-2.65	Deleterious	0.940	Possibly Damaging	0.360	Benign	3.64	Benign	0.00	Affected			0.1971	0.4146		0	-1	6.4	-24.99
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	-0.73	Neutral	0.968	Probably Damaging	0.978	Probably Damaging	5.52	Benign	0.02	Affected			0.1934	0.1000		0	-1	-6.4	24.99
c.3601G>C	E1201Q 2D AIThe SynGAP1 E1201Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a pathogenic impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250											-4.415	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.44	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	1.62	Pathogenic	0.03	Affected			0.0769	0.5473		2	2	0.0	-0.98
c.3781A>C	S1261R 2D AIThe SynGAP1 missense variant S1261R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for S1261R, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-4.363	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.152	Likely Benign	-2.97	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.04	Affected			0.0661	0.2642		0	-1	-3.7	69.11
c.3783C>A	S1261R 2D AIThe SynGAP1 missense variant S1261R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic classification, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-4.363	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.97	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.04	Affected			0.0661	0.2642		0	-1	-3.7	69.11
c.3783C>G	S1261R 2D AIThe SynGAP1 missense variant S1261R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that S1261R is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-4.363	Likely Benign	0.967	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.97	Deleterious	0.996	Probably Damaging	0.898	Possibly Damaging	2.21	Pathogenic	0.04	Affected			0.0661	0.2642		0	-1	-3.7	69.11
c.500A>T	D167V 2D AIThe SynGAP1 D167V 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, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-14.388	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic										0.396	Likely Benign	-4.03	Deleterious	0.535	Possibly Damaging	0.247	Benign	3.92	Benign	0.00	Affected			0.0709	0.6905		-2	-3	7.7	-15.96
c.860A>G	D287G 2D AIThe SynGAP1 missense variant D287G is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, premPS, and Rosetta, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict it to be pathogenic; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of predictions indicates 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	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000											-13.558	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.61	Ambiguous	1.1	0.31	Likely Benign	0.46	Likely Benign	0.38	Likely Benign	0.521	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.59	Pathogenic	0.01	Affected			0.4688	0.7390		1	-1	3.1	-58.04
c.872A>G	Y291C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y291C is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. Based on the unanimous computational evidence, the variant is most likely pathogenic, a conclusion that contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.383842	Uncertain	0.912	0.251	0.000					Uncertain		1				-8.997	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.4	3.51	Destabilizing	3.21	Destabilizing	1.35	Destabilizing	0.505	Likely Pathogenic	-7.37	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.76	Pathogenic	0.01	Affected	3.38	23	0.3053	0.2527		0	-2	3.8	-60.04	205.2	66.1	0.1	0.0	-0.4	0.4	X						X	Potentially Pathogenic	The phenol group of the Tyr291 side chain, located in an anti-parallel β sheet strand (res. Met289-Pro298), packs against hydrophobic residues of the C2 and PH domains (e.g., Leu317, Leu286, Leu284, Pro208, Val209). The phenol ring of Tyr291 also forms favorable Met-aromatic stacking with the methyl group of Met289. In the variant simulation, the thiol group of the Cys291 side chain is not as suitable for the hydrophobic inter-domain space as the phenol ring of Tyr291. Consequently, the structural unity of the PH domain is weakened and ultimately unfolds in the second simulation. Moreover, the residue swap might result in severe detrimental effects on the C2 domain structure and the C2-PH domain tertiary structure assembly during folding.
c.1505G>T	G502V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G502V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: all evaluated algorithms except premPS (which predicts benign) classify the substitution as pathogenic or likely pathogenic. The consensus of high‑accuracy predictors is consistent: AlphaMissense‑Optimized reports a pathogenic effect; 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 destabilizing, pathogenic outcome. In contrast, premPS is the sole tool suggesting a benign impact. Overall, the overwhelming majority of evidence points to a pathogenic effect for G502V, and this conclusion does not conflict with the absence of a ClinVar classification. Thus, the variant is most likely pathogenic, and this assessment is not contradicted by ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000											-15.278	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	3.56	Destabilizing	1.0	5.50	Destabilizing	4.53	Destabilizing	0.43	Likely Benign	0.917	Likely Pathogenic	-8.65	Deleterious	0.999	Probably Damaging	0.944	Probably Damaging	-1.67	Pathogenic	0.00	Affected			0.1406	0.3387		-1	-3	4.6	42.08
c.1607T>C	L536S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L536S is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. The only inconclusive result is from FoldX, which is listed as 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 (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-12.996	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	1.45	Ambiguous	0.3	3.08	Destabilizing	2.27	Destabilizing	1.51	Destabilizing	0.909	Likely Pathogenic	-5.78	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.47	Pathogenic	0.00	Affected			0.2849	0.0577		-3	-2	-4.6	-26.08
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	0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	0.510	Likely Pathogenic	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			0.2024	0.2240		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	0.10	Likely Benign	0.1	0.14	Likely Benign	0.12	Likely Benign	0.40	Likely Benign	0.510	Likely Pathogenic	-4.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	-1.08	Pathogenic	0.14	Tolerated			0.2024	0.2240		1	0	-0.4	14.07
c.1924A>G	K642E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K642E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. No prediction is inconclusive. Overall, the majority of tools lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.287	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.26	Likely Benign	0.1	-0.13	Likely Benign	0.07	Likely Benign	0.40	Likely Benign	0.404	Likely Benign	-3.92	Deleterious	0.116	Benign	0.011	Benign	2.96	Benign	0.03	Affected			0.3865	0.1013		0	1	0.4	0.94
c.1960G>A	E654K 2D AIThe SynGAP1 missense variant E654K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, Foldetta predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic. Overall, the majority of high‑confidence predictions lean toward pathogenicity, and the variant is not contradicted by any ClinVar annotation. Thus, based on the available computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.026892	Structured	0.303029	Uncertain	0.957	0.311	0.000											-12.587	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.3	0.53	Ambiguous	0.33	Likely Benign	-0.17	Likely Benign	0.435	Likely Benign	-3.80	Deleterious	0.921	Possibly Damaging	0.303	Benign	3.44	Benign	0.11	Tolerated			0.2365	0.4224		0	1	-0.4	-0.94
c.1969T>G	W657G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of other in silico predictors (AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FoldX, Rosetta, premPS, Foldetta) all classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-12.559	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	3.04	Destabilizing	0.2	2.80	Destabilizing	2.92	Destabilizing	1.28	Destabilizing	0.389	Likely Benign	-11.16	Deleterious	0.999	Probably Damaging	0.941	Probably Damaging	3.46	Benign	0.15	Tolerated			0.4470	0.0885		-7	-2	0.5	-129.16
c.2777C>A	S926Y 2D AIThe SynGAP1 missense variant S926Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for S926Y, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-6.602	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.444	Likely Benign	-4.53	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.0602	0.4932		-3	-2	-0.5	76.10
c.2948G>T	S983I 2D AIThe SynGAP1 missense variant S983I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that S983I is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-6.259	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.67	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1380	0.4625		-1	-2	5.3	26.08
c.3542A>C	K1181T 2D AIThe SynGAP1 missense variant K1181T is not reported in ClinVar and has no gnomAD allele. Prediction tools show a split: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments give AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the balance of evidence slightly favors pathogenicity, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-4.378	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.146	Likely Benign	-2.30	Neutral	0.999	Probably Damaging	0.963	Probably Damaging	2.65	Benign	0.02	Affected			0.1655	0.3028		0	-1	3.2	-27.07
c.3733G>A	E1245K 2D AIThe SynGAP1 missense variant E1245K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that E1245K is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.911	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.276	Likely Benign	-3.22	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.28	Pathogenic	0.00	Affected			0.1627	0.6574		0	1	-0.4	-0.94
c.470G>C	R157P 2D AIThe SynGAP1 missense variant R157P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates it is likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-11.463	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.450	Likely Benign	-3.38	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.79	Benign	0.00	Affected			0.2438	0.3438		0	-2	2.9	-59.07
c.548A>C	H183P 2D AIThe SynGAP1 missense variant H183P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized also predicts Pathogenic, while the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-18.527	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.410	Likely Benign	-7.18	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.79	Benign	0.01	Affected			0.2143	0.3712		0	-2	1.6	-40.02
c.548A>T	H183L 2D AIThe SynGAP1 missense variant H183L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Pathogenic” verdict (3 pathogenic vs. 1 benign votes). AlphaMissense‑Optimized alone also predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-12.898	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic										0.325	Likely Benign	-8.12	Deleterious	0.421	Benign	0.058	Benign	3.79	Benign	0.01	Affected			0.0911	0.5304		-2	-3	7.0	-23.98
c.650A>G	E217G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E217G missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include polyPhen‑2 HumVar, SIFT, and FATHMM, while those that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts a pathogenic impact, the SGM‑Consensus also indicates a likely pathogenic outcome, and Foldetta’s stability analysis is inconclusive. Overall, the majority of evidence points to a pathogenic effect for E217G, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.278302	Structured	0.404912	Uncertain	0.823	0.284	0.000											-8.076	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	1.13	Ambiguous	0.4	1.87	Ambiguous	1.50	Ambiguous	0.59	Ambiguous	0.684	Likely Pathogenic	-3.93	Deleterious	0.816	Possibly Damaging	0.307	Benign	5.82	Benign	0.06	Tolerated			0.3278	0.6941		0	-2	3.1	-72.06
c.802A>T	I268F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I268F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; only Rosetta and Foldetta are uncertain. 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) remains uncertain. Overall, the consensus of available predictions strongly supports a pathogenic classification for I268F, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.314336	Uncertain	0.951	0.264	0.000											-11.426	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	2.85	Destabilizing	0.7	0.59	Ambiguous	1.72	Ambiguous	1.00	Destabilizing	0.685	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.53	Pathogenic	0.00	Affected			0.0427	0.2158		1	0	-1.7	34.02
c.809A>G	E270G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E270G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. Rosetta also predicts pathogenicity, while FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. No tool predicts a benign effect. 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	0.144935	Structured	0.382573	Uncertain	0.938	0.231	0.125											-13.759	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.2	2.37	Destabilizing	1.80	Ambiguous	0.61	Ambiguous	0.576	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.63	Pathogenic	0.00	Affected			0.3254	0.3876		0	-2	3.1	-72.06
c.1037T>G	V346G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). All available in‑silico predictors classify it as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports pathogenic. With all evidence converging on a deleterious impact and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000											-12.779	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	4.24	Destabilizing	0.2	4.62	Destabilizing	4.43	Destabilizing	2.15	Destabilizing	0.667	Likely Pathogenic	-6.03	Deleterious	0.991	Probably Damaging	0.999	Probably Damaging	1.50	Pathogenic	0.00	Affected			0.2378	0.2522		-1	-3	-4.6	-42.08
c.1199T>G	V400G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V400G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are polyPhen‑2 HumDiv and FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.398279	Structured	0.415488	Uncertain	0.951	0.451	0.000											-11.508	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	4.84	Destabilizing	0.1	5.40	Destabilizing	5.12	Destabilizing	2.40	Destabilizing	0.819	Likely Pathogenic	-5.70	Deleterious	0.335	Benign	0.920	Probably Damaging	5.27	Benign	0.00	Affected			0.2296	0.2522		-1	-3	-4.6	-42.08
c.1202G>A	R401Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438107‑G‑A). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of evaluated algorithms (REVEL, premPS, 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 further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta’s stability prediction is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that R401Q is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000					Uncertain		2	6-33438107-G-A			-11.213	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.1	1.50	Ambiguous	1.23	Ambiguous	1.20	Destabilizing	0.780	Likely Pathogenic	-3.69	Deleterious	0.999	Probably Damaging	0.978	Probably Damaging	5.47	Benign	0.04	Affected	3.38	27	0.3234	0.2269		1	1	1.0	-28.06
c.1266G>C	E422D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E422D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (six benign vs five pathogenic) lean toward a benign effect, but the two most accurate predictors and the consensus vote indicate a pathogenic tendency. Thus, the variant is most likely benign based on the broader tool set, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-7.092	In-Between	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.0	-0.03	Likely Benign	0.18	Likely Benign	0.21	Likely Benign	0.199	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.38	Benign	0.07	Tolerated			0.1686	0.2864		3	2	0.0	-14.03
c.1266G>T	E422D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E422D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of tools (six benign vs five pathogenic) lean toward a benign effect, but the two most accurate predictors and the consensus vote indicate a pathogenic tendency. Thus, the variant is most likely benign based on the broader tool set, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-7.092	In-Between	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.0	-0.03	Likely Benign	0.18	Likely Benign	0.21	Likely Benign	0.199	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.960	Probably Damaging	3.38	Benign	0.07	Tolerated			0.1686	0.2864		3	2	0.0	-14.03
c.1691A>G	E564G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E564G is listed in gnomAD (ID 6‑33440743‑A‑G) but has no ClinVar entry. Prediction tools that assess pathogenicity are unanimous: REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS (uncertain), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a pathogenic effect, while 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 pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment is not contradicted by ClinVar status, which currently contains no entry for E564G. 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								6-33440743-A-G			-15.053	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	1.69	Ambiguous	0.1	2.55	Destabilizing	2.12	Destabilizing	0.80	Ambiguous	0.735	Likely Pathogenic	-6.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.23	Pathogenic	0.04	Affected	3.37	35	0.2749	0.4443		-2	0	3.1	-72.06
c.2453C>A	P818Q 2D AIThe SynGAP1 missense variant P818Q is not listed in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that P818Q is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.855	Likely Benign	0.969	Likely Pathogenic	Likely Pathogenic										0.303	Likely Benign	-4.07	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	1.97	Pathogenic	0.27	Tolerated			0.1569	0.5456		0	-1	-1.9	31.01
c.3617A>C	K1206T 2D AIThe SynGAP1 missense variant K1206T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for K1206T. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-10.161	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.290	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.40	Pathogenic	0.01	Affected			0.1913	0.3354		0	-1	3.2	-27.07
c.3757G>C	A1253P 2D AIThe SynGAP1 missense variant A1253P is not 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 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while AlphaMissense‑Default also predicts pathogenic; however, the majority of tools (five benign vs. four pathogenic) lean toward a benign classification. Thus, based on the current predictions, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.661982	Disordered	0.391377	Uncertain	0.881	0.550	0.750											-11.381	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.062	Likely Benign	-0.63	Neutral	0.568	Possibly Damaging	0.352	Benign	2.74	Benign	0.26	Tolerated			0.1565	0.3514		1	-1	-3.4	26.04
c.3806T>G	V1269G 2D AIThe SynGAP1 missense variant V1269G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus is pathogenic; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-9.927	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.420	Likely Benign	-5.91	Deleterious	0.995	Probably Damaging	0.999	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2180	0.2557		-1	-3	-4.6	-42.08
c.409C>G	L137V 2D AIThe SynGAP1 missense variant L137V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.621	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.118	Likely Benign	-1.75	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.1533	0.2612		2	1	0.4	-14.03
c.443C>G	P148R 2D AIThe SynGAP1 missense variant P148R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. 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 suggests that P148R is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-12.079	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.174	Likely Benign	-3.17	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.92	Benign	0.01	Affected			0.1615	0.3100		0	-2	-2.9	59.07
c.479T>C	L160P 2D AIThe SynGAP1 missense variant L160P 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 high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority pathogenic vote (3 pathogenic vs. 1 benign) and is labeled “Likely Pathogenic.” AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-15.939	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.283	Likely Benign	-3.06	Deleterious	0.001	Benign	0.000	Benign	3.86	Benign	0.00	Affected			0.3589	0.1484		-3	-3	-5.4	-16.04
c.731A>C	E244A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244A missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, and FATHMM, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-11.227	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.39	Likely Benign	0.1	-0.45	Likely Benign	-0.03	Likely Benign	0.82	Ambiguous	0.865	Likely Pathogenic	-4.99	Deleterious	0.970	Probably Damaging	0.584	Possibly Damaging	5.74	Benign	0.01	Affected			0.2672	0.4926		0	-1	5.3	-58.04
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	3.35	Destabilizing	1.1	-2.28	Stabilizing	0.54	Ambiguous	0.61	Ambiguous	0.327	Likely Benign	-8.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.78	Pathogenic	0.11	Tolerated			0.1934	0.3697		-8	-2	-3.4	83.07
c.1243G>C	E415Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, seven tools predict pathogenicity versus six predicting benignity, and the two most reliable predictors (AlphaMissense‑Optimized and SGM‑Consensus) both favor pathogenicity. Therefore, 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	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-9.085	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.29	Likely Benign	0.2	0.22	Likely Benign	0.26	Likely Benign	0.01	Likely Benign	0.236	Likely Benign	-2.63	Deleterious	0.997	Probably Damaging	0.973	Probably Damaging	3.26	Benign	0.08	Tolerated			0.1084	0.3474		2	2	0.0	-0.98
c.1385A>T	K462M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K462M missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, FATHMM, premPS, and the protein‑folding stability method Foldetta; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Rosetta’s output is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also pathogenic, while Foldetta indicates a benign effect on protein stability. No evidence from ClinVar contradicts these findings. Overall, the majority of predictive tools and the consensus score support a pathogenic classification, suggesting that K462M is most likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.837	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	-0.23	Likely Benign	0.1	0.86	Ambiguous	0.32	Likely Benign	0.17	Likely Benign	0.475	Likely Benign	-5.82	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.02	Affected			0.1282	0.3932		0	-1	5.8	3.02
c.1387G>C	D463H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D463H is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, FoldX, SIFT, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, SGM Consensus confirms Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains Uncertain. No evidence from ClinVar contradicts these findings. Overall, the preponderance of computational evidence indicates that D463H is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-13.151	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	0.85	Ambiguous	0.53	Ambiguous	0.57	Ambiguous	0.356	Likely Benign	-5.96	Deleterious	0.996	Probably Damaging	0.852	Possibly Damaging	3.35	Benign	0.11	Tolerated			0.1341	0.6156		1	-1	0.3	22.05
c.1555G>A	E519K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519K missense variant is listed in gnomAD (ID 6‑33438798‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are reported by FoldX, Rosetta, and Foldetta. 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 remains Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E519K, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000								6-33438798-G-A	1	6.20e-7	-13.532	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	-0.55	Ambiguous	0.0	-0.60	Ambiguous	-0.58	Ambiguous	0.06	Likely Benign	0.328	Likely Benign	-3.48	Deleterious	0.996	Probably Damaging	0.987	Probably Damaging	3.28	Benign	0.03	Affected	3.37	35	0.2545	0.3379		1	0	-0.4	-0.94
c.1580A>C	D527A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D527A missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only premPS, while the remaining evaluated methods (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict pathogenicity. FoldX, Rosetta, and Foldetta are inconclusive and are treated as unavailable. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta remains uncertain. Overall, the variant is most likely pathogenic based on the consensus of predictive tools, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000											-15.473	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.9	1.75	Ambiguous	1.28	Ambiguous	-0.24	Likely Benign	0.929	Likely Pathogenic	-7.79	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-2.39	Pathogenic	0.00	Affected			0.2850	0.3799		0	-2	5.3	-44.01
c.1593C>G	C531W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, all of which classify the change as pathogenic. Tools with uncertain or mixed outputs are Rosetta (uncertain) and premPS (uncertain). High‑accuracy assessments further support a damaging impact: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports pathogenic. Based on the overwhelming agreement among pathogenic predictions and the corroborating high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000											-14.107	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	5.27	Destabilizing	3.4	0.63	Ambiguous	2.95	Destabilizing	0.70	Ambiguous	0.510	Likely Pathogenic	-9.12	Deleterious	0.998	Probably Damaging	0.871	Possibly Damaging	-1.25	Pathogenic	0.00	Affected			0.1234	0.3074		-8	-2	-3.4	83.07
c.1607T>G	L536W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L536W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; all of these classify the variant as pathogenic. Tools that are inconclusive (FoldX, Rosetta, Foldetta) do not provide evidence for or against pathogenicity. High‑accuracy assessments further support a damaging impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, while Foldetta’s stability analysis is uncertain. 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	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000											-14.169	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	1.07	Ambiguous	0.6	1.31	Ambiguous	1.19	Ambiguous	1.33	Destabilizing	0.897	Likely Pathogenic	-5.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.50	Pathogenic	0.00	Affected			0.0843	0.2577		-2	-2	-4.7	73.05
c.1747G>T	D583Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D583Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect are Foldetta and premPS, whereas the remaining tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic outcome; FoldX and Rosetta 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 as benign. Overall, the majority of evidence points to a pathogenic effect. 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.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-12.187	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.75	Ambiguous	0.2	-1.10	Ambiguous	-0.18	Likely Benign	0.10	Likely Benign	0.760	Likely Pathogenic	-8.50	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.45	Pathogenic	0.01	Affected			0.0537	0.3868		-4	-3	2.2	48.09
c.1754C>T	A585V 2D AIThe SynGAP1 missense variant A585V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and SIFT, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results (FoldX, Rosetta, Foldetta, premPS) 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, PROVEAN) is Likely Pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.055884	Uncertain	0.880	0.244	0.000											-10.843	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.95	Ambiguous	1.4	1.12	Ambiguous	1.04	Ambiguous	0.51	Ambiguous	0.420	Likely Benign	-3.35	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.27	Pathogenic	0.10	Tolerated			0.1004	0.3496		0	0	2.4	28.05
c.1937T>C	L646P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646P is 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	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000											-12.956	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	7.34	Destabilizing	0.5	12.08	Destabilizing	9.71	Destabilizing	2.72	Destabilizing	0.604	Likely Pathogenic	-4.55	Deleterious	0.999	Probably Damaging	0.926	Probably Damaging	3.17	Benign	0.00	Affected			0.3481	0.1874		-3	-3	-5.4	-16.04
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	-2.84	Deleterious	0.978	Probably Damaging	0.500	Possibly Damaging	4.04	Benign	0.00	Affected			0.1849	0.1115		-2	-3	-7.7	15.96
c.3524G>C	R1175P 2D AIThe SynGAP1 missense variant R1175P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from PROVEAN, ESM1b, and FATHMM, while pathogenic predictions are returned by REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote) predicts benign. No Foldetta stability analysis is available. Overall, the majority of high‑confidence tools lean toward a benign interpretation, and this is consistent with the absence of ClinVar evidence. Therefore, the variant is most likely benign, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.589347	Binding	0.545	0.732	0.375											-4.746	Likely Benign	0.970	Likely Pathogenic	Likely Pathogenic										0.518	Likely Pathogenic	-0.80	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	5.37	Benign	0.00	Affected			0.1715	0.3223		0	-2	2.9	-59.07
c.3554A>C	K1185T 2D AIThe SynGAP1 missense variant K1185T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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, whereas the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.771	Likely Benign	0.970	Likely Pathogenic	Likely Pathogenic										0.153	Likely Benign	-2.41	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.67	Benign	0.13	Tolerated			0.2256	0.2700		0	-1	3.2	-27.07
c.451G>A	D151N 2D AIThe SynGAP1 missense variant D151N has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic. The SGM‑Consensus result (Likely Pathogenic) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors indicates that D151N is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625											-8.479	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.185	Likely Benign	-2.51	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.90	Benign	0.01	Affected			0.1346	0.8186		2	1	0.0	-0.98
c.476T>C	I159T 2D AIThe SynGAP1 missense variant I159T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that predict a pathogenic effect comprise polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while AlphaMissense‑Default also predicts pathogenic. Given that six of the seven individual tools predict pathogenicity versus three predicting benign, the variant is most likely pathogenic. 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.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-12.422	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.218	Likely Benign	-1.69	Neutral	0.981	Probably Damaging	0.966	Probably Damaging	3.86	Benign	0.00	Affected			0.1069	0.0685		0	-1	-5.2	-12.05
c.479T>G	L160R 2D AIThe SynGAP1 missense variant L160R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The protein‑folding stability method Foldetta did not provide a result, so its status is 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 available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-14.539	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.83	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.90	Benign	0.00	Affected			0.1482	0.0702		-3	-2	-8.3	43.03
c.488T>G	F163C 2D AIThe SynGAP1 missense variant F163C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates a likely pathogenic status. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of predictions, including the high‑accuracy tools, point to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-12.221	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-2.99	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	4.01	Benign	0.00	Affected			0.2860	0.1232		-4	-2	-0.3	-44.04
c.521T>G	M174R 2D AIThe SynGAP1 missense variant M174R is not reported in ClinVar and is absent from gnomAD. Computational assessment shows a split in predictions: 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. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are unavailable, so no additional stability evidence is provided. 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		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-9.114	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic										0.308	Likely Benign	-3.15	Deleterious	0.139	Benign	0.039	Benign	4.05	Benign	0.01	Affected			0.1545	0.1037		0	-1	-6.4	24.99
c.758A>T	N253I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N253I is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (ID 6‑33435609‑A‑T). Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Benign predictions are limited to premPS 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) 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 the ClinVar status, which simply lacks an entry. 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								6-33435609-A-T	1	6.20e-7	-15.241	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	2.95	Destabilizing	0.1	5.56	Destabilizing	4.26	Destabilizing	0.25	Likely Benign	0.836	Likely Pathogenic	-7.83	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	5.57	Benign	0.01	Affected	3.39	15	0.0803	0.7553		-3	-2	8.0	-0.94
c.850C>T	L284F 2D AIThe SynGAP1 missense variant L284F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Taken together, the overwhelming majority of evidence indicates that the variant is most likely pathogenic, 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	C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000											-11.656	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	1.9	1.05	Ambiguous	1.55	Ambiguous	0.62	Ambiguous	0.654	Likely Pathogenic	-3.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.69	Pathogenic	0.01	Affected			0.0515	0.2779		2	0	-1.0	34.02
c.889A>C	K297Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K297Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, Rosetta, and Foldetta. In contrast, the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX is uncertain and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the preponderance of evidence points to a pathogenic effect for K297Q. 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	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-8.393	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.66	Ambiguous	0.3	0.14	Likely Benign	0.40	Likely Benign	1.06	Destabilizing	0.450	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.4768	0.1738		1	1	0.4	-0.04
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	0.33	Likely Benign	0.1	-0.08	Likely Benign	0.13	Likely Benign	0.15	Likely Benign	0.212	Likely Benign	-4.94	Deleterious	0.891	Possibly Damaging	0.315	Benign	1.58	Pathogenic	0.01	Affected			0.2014	0.4048		0	-1	3.2	-27.07
c.1079A>G	E360G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: premPS is the only tool that predicts a benign outcome, whereas all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the substitution as pathogenic. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized returns a pathogenic prediction; 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 effect. Taken together, the overwhelming majority of evidence points to a pathogenic impact for E360G, and this conclusion is consistent with the absence of a ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-13.972	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	2.55	Destabilizing	0.1	2.99	Destabilizing	2.77	Destabilizing	0.31	Likely Benign	0.569	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.986	Probably Damaging	1.68	Pathogenic	0.04	Affected			0.2993	0.6935		0	-2	3.1	-72.06
c.1080G>C	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and SIFT. In contrast, a majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus remains Likely Pathogenic, while Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E360D. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.1080G>T	E360D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include REVEL, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-9.383	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.0	0.63	Ambiguous	0.82	Ambiguous	0.11	Likely Benign	0.290	Likely Benign	-2.76	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.77	Pathogenic	0.07	Tolerated			0.2339	0.5735		3	2	0.0	-14.03
c.1207A>C	K403Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. The premPS assessment is uncertain and does not influence the overall consensus. High‑accuracy analyses show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. 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 because no ClinVar claim exists 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											-12.479	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.36	Likely Benign	0.0	0.27	Likely Benign	0.32	Likely Benign	0.70	Ambiguous	0.376	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.76	Benign	0.01	Affected			0.4405	0.1954		1	1	0.4	-0.04
c.1307A>C	E436A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436A is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include Foldetta, premPS, and FATHMM, whereas the majority of algorithms—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. Two high‑accuracy predictors give concordant results: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. No prediction is missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for E436A, 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	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-12.678	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.03	Ambiguous	0.0	-0.88	Ambiguous	0.08	Likely Benign	0.23	Likely Benign	0.825	Likely Pathogenic	-5.68	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	4.65	Benign	0.05	Affected			0.3901	0.5116		0	-1	5.3	-58.04
c.1513T>A	Y505N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505N is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools largely agree on a deleterious effect: all available predictors except FATHMM classify the variant as pathogenic or likely pathogenic. The benign group contains only FATHMM, whereas the pathogenic group includes SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a damaging outcome: 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. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.292227	Uncertain	0.909	0.188	0.000											-14.139	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	3.38	Destabilizing	0.0	4.33	Destabilizing	3.86	Destabilizing	2.47	Destabilizing	0.695	Likely Pathogenic	-8.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.60	Benign	0.00	Affected			0.2124	0.0612		-2	-2	-2.2	-49.07
c.167T>C	L56P 2D AIThe SynGAP1 missense variant L56P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-9.991	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic										0.307	Likely Benign	-2.62	Deleterious	0.943	Possibly Damaging	0.944	Probably Damaging	3.77	Benign	0.00	Affected			0.3806	0.1342		-3	-3	-5.4	-16.04
c.174G>A	M58I 2D AIThe SynGAP1 missense variant M58I is not reported in ClinVar (ClinVar ID = None) but is present in gnomAD (ID = 6‑33423583‑G‑A). 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 likely benign; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this is not contradicted by ClinVar status. Thus, based on the available evidence, the variant is most likely benign. 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								6-33423583-G-A	1	6.20e-7	-2.153	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-0.55	Neutral	0.006	Benign	0.091	Benign	4.21	Benign	0.00	Affected	4.32	1	0.1397	0.3848		1	2	2.6	-18.03
c.174G>C	M58I 2D AIThe SynGAP1 missense variant M58I is 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000											-2.153	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-0.55	Neutral	0.006	Benign	0.091	Benign	4.21	Benign	0.00	Affected	4.32	1	0.1397	0.3848		1	2	2.6	-18.03
c.174G>T	M58I 2D AIThe SynGAP1 missense variant M58I is 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions (seven benign vs. three pathogenic) suggest the variant is most likely benign, 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 Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000											-2.153	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-0.55	Neutral	0.006	Benign	0.091	Benign	4.21	Benign	0.00	Affected	4.32	1	0.1397	0.3848		1	2	2.6	-18.03
c.178G>T	D60Y 2D AIThe SynGAP1 D60Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the D60Y variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000											-7.748	In-Between	0.971	Likely Pathogenic	Likely Pathogenic										0.221	Likely Benign	-2.60	Deleterious	0.972	Probably Damaging	0.969	Probably Damaging	3.90	Benign	0.00	Affected			0.0517	0.7790		-4	-3	2.2	48.09
c.1901C>T	A634V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score, while only FATHMM predicts a benign outcome; Rosetta remains inconclusive. High‑accuracy assessments reinforce the pathogenic trend: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Taken together, the overwhelming majority of evidence supports a pathogenic effect for A634V, which is in contrast to its current ClinVar classification of uncertain significance. Therefore, the variant is most likely pathogenic, contradicting its ClinVar uncertain status. 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					Uncertain		1				-12.612	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	2.67	Destabilizing	0.2	1.44	Ambiguous	2.06	Destabilizing	1.14	Destabilizing	0.631	Likely Pathogenic	-3.98	Deleterious	0.997	Probably Damaging	0.976	Probably Damaging	2.55	Benign	0.01	Affected			0.1215	0.4371		0	0	2.4	28.05
c.1948A>G	N650D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N650D is not 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, and FATHMM. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) yield uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the majority of available predictions support a pathogenic impact. The variant is most likely pathogenic based on the consensus of predictive tools, 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	0.086953	Structured	0.361944	Uncertain	0.961	0.357	0.000											-14.267	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.14	Ambiguous	0.3	0.61	Ambiguous	0.88	Ambiguous	0.91	Ambiguous	0.389	Likely Benign	-4.98	Deleterious	0.591	Possibly Damaging	0.185	Benign	2.99	Benign	0.03	Affected			0.2320	0.2973		2	1	0.0	0.98
c.2771C>T	P924L 2D AIThe SynGAP1 missense variant P924L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that P924L is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.361	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.422	Likely Benign	-6.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1771	0.4941		-3	-3	5.4	16.04
c.2954G>T	S985I 2D AIThe SynGAP1 missense variant S985I 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 remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that S985I is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-7.858	In-Between	0.971	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-2.78	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.50	Benign	0.00	Affected			0.1367	0.5206		-1	-2	5.3	26.08
c.349A>C	S117R 2D AIThe SynGAP1 missense variant S117R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-4.187	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.276	Likely Benign	-1.81	Neutral	0.845	Possibly Damaging	0.326	Benign	3.70	Benign	0.01	Affected	3.61	5	0.1040	0.3770		-1	0	-3.7	69.11
c.3503T>A	I1168N 2D AIThe SynGAP1 missense variant I1168N is not 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) which labels the variant as Likely Benign. In contrast, tools that predict a pathogenic effect are PolyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the evidence is split evenly between benign and pathogenic predictions, with no consensus from the most accurate methods. Consequently, the variant’s pathogenicity is uncertain and 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		0.642678	Disordered	0.763262	Binding	0.423	0.796	0.500											-4.269	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.455	Likely Benign	-1.79	Neutral	0.998	Probably Damaging	0.987	Probably Damaging	5.53	Benign	0.01	Affected			0.0943	0.0969		-2	-3	-8.0	0.94
c.351C>A	S117R 2D AIThe SynGAP1 missense variant S117R has no ClinVar entry and is not reported 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Overall, the majority of tools (six benign vs. four pathogenic) and the consensus evidence lean 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		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-4.187	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.144	Likely Benign	-1.81	Neutral	0.845	Possibly Damaging	0.326	Benign	3.70	Benign	0.01	Affected	3.61	5	0.1040	0.3770		-1	0	-3.7	69.11
c.351C>G	S117R 2D AIThe SynGAP1 missense variant S117R is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33432216‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a pathogenic ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625								6-33432216-C-G	1	6.20e-7	-4.187	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.144	Likely Benign	-1.81	Neutral	0.845	Possibly Damaging	0.326	Benign	3.70	Benign	0.01	Affected	3.61	5	0.1040	0.3770		-1	0	-3.7	69.11
c.3805G>C	V1269L 2D AIThe SynGAP1 missense variant V1269L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.572	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.299	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0683	0.4082		2	1	-0.4	14.03
c.3805G>T	V1269L 2D AIThe SynGAP1 missense variant V1269L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.572	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.299	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0683	0.4082		2	1	-0.4	14.03
c.3809A>G	E1270G 2D AIThe SynGAP1 missense variant E1270G is listed in gnomAD (ID 6‑33447857‑A‑G) and has no ClinVar entry. Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic, while Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the absence of a benign consensus, the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250								6-33447857-A-G			-12.022	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic										0.385	Likely Benign	-5.90	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	2.05	Pathogenic	0.00	Affected	3.77	5	0.2415	0.5452		-2	0	3.1	-72.06
c.552G>C	E184D 2D AIThe SynGAP1 E184D missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-6.753	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-2.55	Deleterious	0.930	Possibly Damaging	0.584	Possibly Damaging	3.52	Benign	0.00	Affected			0.2249	0.5394		3	2	0.0	-14.03
c.552G>T	E184D 2D AIThe SynGAP1 E184D missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs. three benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-6.753	Likely Benign	0.971	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-2.55	Deleterious	0.930	Possibly Damaging	0.584	Possibly Damaging	3.52	Benign	0.00	Affected			0.2249	0.5394		3	2	0.0	-14.03
c.836G>C	R279P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R279P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic. No tool predicts a benign effect. FoldX reports an uncertain outcome, but Rosetta, Foldetta, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all predict pathogenicity. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus, based on a majority vote of the aforementioned predictors, 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 is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.309382	Uncertain	0.887	0.257	0.125											-14.926	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.42	Ambiguous	0.9	4.27	Destabilizing	2.85	Destabilizing	1.21	Destabilizing	0.626	Likely Pathogenic	-5.01	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.90	Pathogenic	0.02	Affected			0.2179	0.3281		0	-2	2.9	-59.07
c.880A>G	T294A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T294A missense variant is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain call is FoldX. High‑accuracy methods give consistent results: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts Likely Pathogenic, and Foldetta predicts Pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.316932	Uncertain	0.919	0.267	0.125											-12.371	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	2.27	Destabilizing	2.07	Destabilizing	1.05	Destabilizing	0.719	Likely Pathogenic	-4.60	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	-0.18	Pathogenic	0.03	Affected			0.3687	0.3494		1	0	2.5	-30.03
c.1202G>T	R401L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401L is not reported in ClinVar and is present in gnomAD (ID 6‑33438107‑G‑T). Prediction tools that classify the variant as benign include Rosetta, FATHMM, and premPS, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX alone is available. Based on the preponderance of pathogenic predictions and the corroborating high‑accuracy tools, R401L is most likely pathogenic; this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000								6-33438107-G-T	1	6.20e-7	-12.280	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	-1.52	Ambiguous	0.1	-0.23	Likely Benign	-0.88	Ambiguous	0.22	Likely Benign	0.858	Likely Pathogenic	-6.42	Deleterious	0.997	Probably Damaging	0.987	Probably Damaging	5.44	Benign	0.02	Affected	3.38	27	0.1972	0.4263		-2	-3	8.3	-43.03
c.1242G>A	M414I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 M414I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta is also inconclusive. Overall, more tools (five) predict pathogenicity than benign (four), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-6.203	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.0	0.86	Ambiguous	0.85	Ambiguous	0.84	Ambiguous	0.265	Likely Benign	-3.00	Deleterious	0.870	Possibly Damaging	0.801	Possibly Damaging	3.44	Benign	0.36	Tolerated			0.1168	0.3161		2	1	2.6	-18.03
c.1242G>C	M414I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta is uncertain, so these results are treated as unavailable. Overall, the majority of evaluated tools (5 pathogenic vs 4 benign) and the single high‑accuracy pathogenic prediction support a likely pathogenic classification. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-6.203	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.0	0.86	Ambiguous	0.85	Ambiguous	0.84	Ambiguous	0.265	Likely Benign	-3.00	Deleterious	0.870	Possibly Damaging	0.801	Possibly Damaging	3.44	Benign	0.36	Tolerated			0.1168	0.3161		2	1	2.6	-18.03
c.1242G>T	M414I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta is uncertain, so these results are treated as unavailable. Overall, the majority of evaluated tools (5 pathogenic vs 4 benign) and the single high‑accuracy pathogenic prediction support a likely pathogenic classification. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-6.203	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic	0.83	Ambiguous	0.0	0.86	Ambiguous	0.85	Ambiguous	0.84	Ambiguous	0.265	Likely Benign	-3.00	Deleterious	0.870	Possibly Damaging	0.801	Possibly Damaging	3.44	Benign	0.36	Tolerated			0.1168	0.3161		2	1	2.6	-18.03
c.1316T>A	L439Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000											-11.162	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	2.50	Destabilizing	0.1	2.06	Destabilizing	2.28	Destabilizing	1.35	Destabilizing	0.575	Likely Pathogenic	-5.15	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.21	Benign	0.01	Affected			0.1065	0.0488		-2	-2	-7.3	14.97
c.157G>T	G53W 2D AIThe SynGAP1 missense variant G53W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of available predictions (six pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-11.012	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.243	Likely Benign	-1.69	Neutral	0.998	Probably Damaging	0.993	Probably Damaging	4.08	Benign	0.00	Affected			0.0678	0.5071		-7	-2	-0.5	129.16
c.1786C>T	R596C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R596C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33440838‑C‑T). Prediction tools that indicate a benign effect include only premPS. All other evaluated algorithms—REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic or likely pathogenic, while Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. **Thus, the variant is most likely pathogenic based on the collective predictions, which does not contradict the ClinVar uncertain status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.017797	Structured	0.135423	Uncertain	0.918	0.134	0.000					Conflicting		2	6-33440838-C-T	6	3.72e-6	-10.805	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	2.94	Destabilizing	0.0	1.49	Ambiguous	2.22	Destabilizing	-0.03	Likely Benign	0.633	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.41	Pathogenic	0.00	Affected	3.37	35	0.3429	0.2211		-4	-3	7.0	-53.05	230.7	97.9	-0.1	0.0	-0.3	0.4		X		X				Potentially Pathogenic	The guanidinium group of Arg596, located in an α helix (res. Glu582-Met603), forms a salt bridge with the carboxylate group of Glu495 from another α helix (res. Leu489-Glu519). In the WT simulations, the side chain of Arg596 hydrogen bonds with the backbone carbonyl groups of Asn487, Glu486, Arg485, and Phe484. Additionally, Arg596 can hydrogen bond with the carboxamide group of the Asn487 side chain on an opposing loop that links two α helices (res. Ala461-Arg475, res. Leu489-Glu519).In the variant simulations, the thiol group of the Cys596 side chain is unable to form salt bridges or any of the hydrogen bonds that the Arg596 side chain can. Thus, the residue swap could affect the tertiary structure assembly more profoundly than observed in the simulations. Notably, Arg596 plays a key role in positioning the aforementioned loop, which is crucial for the placement of the “arginine finger” or the Arg485 side chain during RasGTPase activation.
c.1870A>C	T624P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T624P 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 outputs, 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.	Likely Pathogenic	GAP	0.137348	Structured	0.052894	Uncertain	0.962	0.217	0.000											-15.681	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	3.64	Destabilizing	0.2	9.04	Destabilizing	6.34	Destabilizing	0.83	Ambiguous	0.914	Likely Pathogenic	-5.94	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.55	Pathogenic	0.01	Affected			0.1500	0.3569		0	-1	-0.9	-3.99
c.1885G>C	V629L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V629L has no ClinVar entry and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, and FATHMM, whereas the majority of algorithms predict a pathogenic outcome: Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools report uncertainty: Foldetta and premPS. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also indicates likely pathogenic, while Foldetta remains uncertain. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.034796	Uncertain	0.970	0.236	0.000											-12.785	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.06	Likely Benign	0.2	2.26	Destabilizing	1.16	Ambiguous	0.54	Ambiguous	0.391	Likely Benign	-2.79	Deleterious	0.975	Probably Damaging	0.958	Probably Damaging	3.22	Benign	0.02	Affected			0.0805	0.3336		2	1	-0.4	14.03
c.1907T>G	F636C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636C is reported in gnomAD (ID 6‑33440959‑T‑G) but has no ClinVar entry. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Only FATHMM predicts a benign outcome; FoldX is uncertain and therefore not counted as evidence. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000								6-33440959-T-G	3	1.86e-6	-13.287	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.1	2.65	Destabilizing	2.20	Destabilizing	1.22	Destabilizing	0.612	Likely Pathogenic	-7.67	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.40	Benign	0.04	Affected	3.37	34	0.2301	0.0830		-2	-4	-0.3	-44.04
c.197C>T	P66L 2D AIThe SynGAP1 missense variant P66L is 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, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized calling the variant pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are not available. Overall, the predictions are split evenly between benign and pathogenic, with high‑accuracy tools providing opposing conclusions. Consequently, the variant’s impact remains uncertain and 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		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-2.437	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.48	Neutral	0.909	Possibly Damaging	0.713	Possibly Damaging	3.92	Benign	0.00	Affected			0.2412	0.6687		-3	-3	5.4	16.04
c.2524T>C	S842P 2D AIThe SynGAP1 missense variant S842P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity largely agree: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict a deleterious effect. Only REVEL classifies the variant as benign. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus indicates “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, indicates that S842P is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-13.890	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.309	Likely Benign	-3.43	Deleterious	0.995	Probably Damaging	0.892	Possibly Damaging	1.99	Pathogenic	0.00	Affected			0.1494	0.5342		1	-1	-0.8	10.04
c.3485C>A	P1162H 2D AIThe SynGAP1 missense variant P1162H is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as Pathogenic, whereas the SGM‑Consensus (majority vote) indicates Likely Benign; Foldetta results are unavailable. Overall, the majority of tools (six benign vs. four pathogenic) lean toward a benign interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction conflicts with the consensus. Because ClinVar contains no entry, there is no contradiction with clinical database status. Based on the collective predictions, the variant is most likely benign, though the AlphaMissense‑Optimized result suggests caution. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375											-3.733	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.168	Likely Benign	-2.46	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.67	Benign	0.17	Tolerated			0.1481	0.5001		0	-2	-1.6	40.02
c.3496G>C	A1166P 2D AIThe SynGAP1 missense variant A1166P is not 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. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as Pathogenic, whereas the SGM‑Consensus (majority vote) indicates Likely Benign; Foldetta results are unavailable. Overall, the predictions are mixed, with a slight bias toward benign, and there is no ClinVar entry to contradict the current assessment. Thus, the variant is most likely benign based on the collective evidence, though high‑accuracy tools provide conflicting signals. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.811691	Binding	0.381	0.803	0.375											-2.890	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.468	Likely Benign	-1.09	Neutral	0.999	Probably Damaging	0.993	Probably Damaging	5.29	Benign	0.23	Tolerated			0.1774	0.4237		1	-1	-3.4	26.04
c.3503T>G	I1168S 2D AISynGAP1 missense variant I1168S has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the evidence is split, with an equal number of benign and pathogenic calls, and the high‑accuracy predictions are contradictory. Therefore, the variant is not conclusively predicted to be benign or pathogenic, and there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.763262	Binding	0.423	0.796	0.500											-2.212	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.442	Likely Benign	-1.46	Neutral	0.998	Probably Damaging	0.958	Probably Damaging	5.67	Benign	0.01	Affected			0.3247	0.1540		-1	-2	-5.3	-26.08
c.3547T>G	Y1183D 2D AISynGAP1 missense variant Y1183D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools show mixed results: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, a majority‑vote model of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts the variant as likely benign. High‑accuracy assessments further indicate AlphaMissense‑Optimized as pathogenic, whereas Foldetta (FoldX‑MD/Rosetta stability analysis) is not available for this residue. Overall, the balance of evidence leans toward a benign effect, and this assessment does not conflict with ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500											-2.718	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.097	Likely Benign	-1.10	Neutral	0.986	Probably Damaging	0.787	Possibly Damaging	2.83	Benign	0.61	Tolerated			0.4602	0.0243		-4	-3	-2.2	-48.09
c.3560T>A	M1187K 2D AIThe SynGAP1 missense variant M1187K is 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, ESM1b, and FATHMM, while those that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none is present). 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 Benign	Coiled-coil	0.562014	Disordered	0.499801	Uncertain	0.597	0.636	0.625											-3.712	Likely Benign	0.972	Likely Pathogenic	Likely Pathogenic										0.594	Likely Pathogenic	-0.71	Neutral	0.968	Probably Damaging	0.969	Probably Damaging	5.54	Benign	0.03	Affected			0.1758	0.0851		0	-1	-5.8	-3.02
c.464G>T	S155I 2D AIThe SynGAP1 missense variant S155I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and the Foldetta stability analysis is unavailable. Taken together, the majority of evidence points to a pathogenic impact for S155I. 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		0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-11.298	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic										0.264	Likely Benign	-2.70	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	3.81	Benign	0.00	Affected			0.0764	0.5711		-1	-2	5.3	26.08
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	1.33	Ambiguous	0.6	1.36	Ambiguous	1.35	Ambiguous	0.13	Likely Benign	0.826	Likely Pathogenic	-4.43	Deleterious	0.929	Possibly Damaging	0.519	Possibly Damaging	5.93	Benign	0.04	Affected			0.1972	0.4336		0	-2	2.9	-59.07
c.948C>A	N316K 2D AIThe SynGAP1 missense variant N316K is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL and SIFT, whereas the majority of tools predict a pathogenic outcome: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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) as uncertain. No other high‑confidence predictions are available. Overall, the preponderance of evidence points to a pathogenic effect for N316K, 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	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-10.711	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.52	Ambiguous	0.7	0.86	Ambiguous	0.69	Ambiguous	0.67	Ambiguous	0.254	Likely Benign	-3.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.77	Pathogenic	0.13	Tolerated			0.2220	0.6593		1	0	-0.4	14.07
c.948C>G	N316K 2D AISynGAP1 missense variant N316K 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 and SIFT, whereas a majority of tools predict pathogenicity: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, yields an uncertain result and is treated as unavailable evidence. Overall, the preponderance of computational predictions indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-10.711	Likely Pathogenic	0.972	Likely Pathogenic	Likely Pathogenic	0.52	Ambiguous	0.7	0.86	Ambiguous	0.69	Ambiguous	0.67	Ambiguous	0.254	Likely Benign	-3.87	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.77	Pathogenic	0.13	Tolerated			0.2220	0.6593		1	0	-0.4	14.07
c.1001A>T	K334M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K334M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, and premPS. In contrast, the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. Foldetta and Rosetta provide uncertain results. Focusing on high‑accuracy methods, AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus confirms a Likely Pathogenic status, and Foldetta remains inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K334M, and this assessment does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.377384	Structured	0.325972	Uncertain	0.544	0.414	0.500											-10.530	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.0	0.56	Ambiguous	0.50	Ambiguous	0.14	Likely Benign	0.323	Likely Benign	-5.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.77	Pathogenic	0.01	Affected			0.1027	0.3690		0	-1	5.8	3.02
c.1079A>T	E360V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E360V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only premPS, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the overwhelming majority of reliable predictors classify E360V as pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.250310	Structured	0.421183	Uncertain	0.955	0.498	0.250											-14.388	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.11	Ambiguous	1.06	Ambiguous	0.03	Likely Benign	0.627	Likely Pathogenic	-6.43	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	1.57	Pathogenic	0.00	Affected			0.1143	0.8670		-2	-2	7.7	-29.98
c.1463C>T	T488M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T488M is listed in ClinVar with an uncertain significance (ClinVar ID 2824521.0) and is present in gnomAD (ID 6‑33438495‑C‑T). Prediction tools that indicate a benign effect include premPS and FATHMM, whereas the majority of algorithms predict a pathogenic outcome: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as inconclusive. No other tools provide definitive evidence. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.206376	Structured	0.332663	Uncertain	0.928	0.233	0.125					Uncertain		1	6-33438495-C-T	2	1.24e-6	-12.459	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.66	Ambiguous	0.3	1.62	Ambiguous	1.14	Ambiguous	0.46	Likely Benign	0.746	Likely Pathogenic	-5.70	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.21	Benign	0.00	Affected	3.37	35	0.1027	0.4857		-1	-1	2.6	30.09
c.1526C>A	A509D 2D AIThe SynGAP1 missense variant A509D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Pathogenic” verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a pathogenic effect. 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.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000											-17.026	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	4.02	Destabilizing	1.6	3.09	Destabilizing	3.56	Destabilizing	1.36	Destabilizing	0.915	Likely Pathogenic	-4.94	Deleterious	0.963	Probably Damaging	0.844	Possibly Damaging	-1.40	Pathogenic	0.00	Affected			0.1610	0.1360		0	-2	-5.3	44.01
c.1715G>T	W572L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W572L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only SIFT, which scores the variant as benign. All other evaluated predictors—REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a pathogenic effect. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.150080	Structured	0.039626	Uncertain	0.935	0.256	0.000											-15.765	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	2.62	Destabilizing	0.1	3.97	Destabilizing	3.30	Destabilizing	0.90	Ambiguous	0.591	Likely Pathogenic	-11.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.91	Pathogenic	0.31	Tolerated			0.2246	0.2837		-2	-2	4.7	-73.05
c.1748A>T	D583V 2D 3DClick to see structure in 3D Viewer AISynGAP1 D583V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, Foldetta, premPS, and SIFT, whereas pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and ESM1b give uncertain results. High‑accuracy methods give a split view: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the majority of tools support a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000											-7.796	In-Between	0.973	Likely Pathogenic	Likely Pathogenic	1.20	Ambiguous	0.2	-0.31	Likely Benign	0.45	Likely Benign	0.12	Likely Benign	0.839	Likely Pathogenic	-8.63	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	-1.40	Pathogenic	0.08	Tolerated			0.0778	0.4090		-2	-3	7.7	-15.96
c.2150T>G	L717R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717R is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while the remaining 13 tools (SGM‑Consensus, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the majority‑vote SGM Consensus) predict pathogenicity; FoldX is uncertain. High‑accuracy methods reinforce a pathogenic verdict: AlphaMissense‑Optimized scores it as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta also predicts pathogenic. No prediction is missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-11.352	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.1	3.78	Destabilizing	2.72	Destabilizing	1.57	Destabilizing	0.353	Likely Benign	-4.98	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.28	Benign	0.00	Affected			0.1169	0.0558		-3	-2	-8.3	43.03
c.253A>T	T85S 2D AIThe SynGAP1 missense variant T85S is not reported in ClinVar and is absent from gnomAD. 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, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of conventional predictors lean toward a benign impact, but the high‑accuracy AlphaMissense‑Optimized tool suggests pathogenicity, creating a conflict. No ClinVar entry exists, so there is no reported status to contradict. Based on the collective evidence, the variant is most likely benign, though the high‑accuracy prediction indicates uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-4.171	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.103	Likely Benign	-1.37	Neutral	0.113	Benign	0.011	Benign	3.87	Benign	0.00	Affected			0.2590	0.3569		1	1	-0.1	-14.03
c.2683A>C	S895R 2D AIThe SynGAP1 missense variant S895R is reported in ClinVar as not yet classified and is present in gnomAD (ID 6‑33443235‑A‑C). Consensus from multiple in silico predictors shows a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. When grouping by agreement, the benign group contains five tools, whereas the pathogenic group contains four. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a benign effect, and this conclusion does not conflict with the current ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750								6-33443235-A-C	1	6.20e-7	-4.746	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.167	Likely Benign	-1.72	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.64	Benign	0.10	Tolerated	4.32	4	0.0949	0.4046		-1	0	-3.7	69.11
c.2685T>A	S895R 2D AIThe SynGAP1 missense variant S895R is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect, and this is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750											-4.746	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.123	Likely Benign	-1.72	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.64	Benign	0.10	Tolerated	4.32	4	0.0949	0.4046		-1	0	-3.7	69.11
c.2685T>G	S895R 2D AIThe SynGAP1 missense variant S895R is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750											-4.746	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.123	Likely Benign	-1.72	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.64	Benign	0.10	Tolerated	4.32	4	0.0949	0.4046		-1	0	-3.7	69.11
c.3110T>C	I1037T 2D AIThe SynGAP1 missense variant I1037T is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443662‑T‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of predictions (seven benign vs. two pathogenic) indicate that the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.939629	Disordered	0.986140	Binding	0.309	0.774	0.625								6-33443662-T-C	1	6.21e-7	-2.565	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.066	Likely Benign	0.40	Neutral	0.292	Benign	0.110	Benign	2.79	Benign	0.34	Tolerated	3.77	5	0.1071	0.2175		-1	0	-5.2	-12.05
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	-1.81	Neutral	0.997	Probably Damaging	0.898	Possibly Damaging	2.51	Benign	0.00	Affected	3.88	3	0.1969	0.6422		1	0	-0.4	-0.94
c.3542A>T	K1181M 2D AIThe SynGAP1 K1181M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (7 out of 10) indicate pathogenicity, so 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.		Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-4.429	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.172	Likely Benign	-2.54	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	2.60	Benign	0.01	Affected			0.0741	0.3366		0	-1	5.8	3.02
c.3581G>C	R1194T 2D AIThe SynGAP1 missense variant R1194T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are split, with four tools supporting benign and four supporting pathogenic, and the high‑accuracy consensus is conflicting. Based on the available evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-4.875	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.402	Likely Benign	-1.96	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.50	Benign	0.02	Affected			0.1866	0.3706		-1	-1	3.8	-55.08
c.3673T>C	S1225P 2D AIThe SynGAP1 missense variant S1225P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (five pathogenic vs. four benign) indicate a pathogenic impact. This conclusion is not contradicted by ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.513880	Disordered	0.441915	Uncertain	0.891	0.544	0.500											-12.278	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic										0.489	Likely Benign	-2.07	Neutral	0.784	Possibly Damaging	0.575	Possibly Damaging	5.36	Benign	0.25	Tolerated			0.1499	0.4570		1	-1	-0.8	10.04
c.479T>A	L160Q 2D AIThe SynGAP1 missense variant L160Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-16.626	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic										0.227	Likely Benign	-2.83	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.87	Benign	0.00	Affected			0.1248	0.1060		-2	-2	-7.3	14.97
c.617T>C	I206T 2D AIThe SynGAP1 I206T 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give consistent results: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overall evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not currently listed. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.298791	Structured	0.405123	Uncertain	0.863	0.391	0.125											-10.812	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	2.43	Destabilizing	0.5	2.68	Destabilizing	2.56	Destabilizing	1.94	Destabilizing	0.252	Likely Benign	-3.78	Deleterious	0.421	Benign	0.156	Benign	3.65	Benign	0.00	Affected			0.0830	0.0669		0	-1	-5.2	-12.05
c.632G>T	S211I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S211I missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM; pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. No evidence from FoldX or Rosetta is available. Overall, the preponderance of evidence indicates 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	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-17.090	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	1.1	1.05	Ambiguous	1.06	Ambiguous	0.12	Likely Benign	0.251	Likely Benign	-4.94	Deleterious	0.995	Probably Damaging	0.767	Possibly Damaging	3.90	Benign	0.01	Affected			0.0909	0.5220		-1	-2	5.3	26.08
c.671C>T	T224I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 T224I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. With an equal split of benign and pathogenic calls overall, the two high‑accuracy pathogenic predictions outweigh the single high‑accuracy benign prediction, indicating that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.360921	Uncertain	0.848	0.315	0.125											-8.831	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.49	Likely Benign	0.2	0.35	Likely Benign	0.42	Likely Benign	0.02	Likely Benign	0.657	Likely Pathogenic	-3.47	Deleterious	0.608	Possibly Damaging	0.154	Benign	5.58	Benign	0.38	Tolerated			0.1015	0.7225		0	-1	5.2	12.05
c.869T>C	L290P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L290P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity unanimously favor a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenicity. No tool in the dataset predicts a benign outcome; the remaining tools (FoldX, Rosetta, Foldetta, premPS) return uncertain results, which are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is inconclusive. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.399723	Uncertain	0.904	0.255	0.000											-11.796	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.79	Ambiguous	0.1	1.10	Ambiguous	0.95	Ambiguous	0.56	Ambiguous	0.727	Likely Pathogenic	-6.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.01	Pathogenic	0.03	Affected			0.3646	0.1703		-3	-3	-5.4	-16.04
c.878G>A	R293H 2D AISynGAP1 missense variant R293H is listed in ClinVar with an uncertain significance (ClinVar ID 3901513.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL and premPS, whereas the remaining 13 tools—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, classifies the variant as pathogenic. Overall, the preponderance of evidence indicates that R293H is most likely pathogenic, a conclusion that does not contradict the current ClinVar uncertain status. 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					Uncertain		1				-13.009	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	4.45	Destabilizing	2.3	2.12	Destabilizing	3.29	Destabilizing	0.32	Likely Benign	0.438	Likely Benign	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.04	Affected			0.3120	0.2573		2	0	1.3	-19.05
c.994G>C	D332H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D332H has no ClinVar entry and is absent from gnomAD. Functional prediction tools that agree on a benign effect are Rosetta and premPS, whereas the majority of predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the change 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) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Taken together, the preponderance of evidence indicates that D332H 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	C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-13.255	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	1.50	Ambiguous	0.4	-0.28	Likely Benign	0.61	Ambiguous	0.22	Likely Benign	0.505	Likely Pathogenic	-5.63	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.23	Pathogenic	0.01	Affected			0.1005	0.4542		1	-1	0.3	22.05
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	3.19	Destabilizing	0.6	4.32	Destabilizing	3.76	Destabilizing	0.96	Ambiguous	0.882	Likely Pathogenic	-5.89	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.49	Pathogenic	0.00	Affected			0.2024	0.3759		0	-1	-0.9	-3.99
c.1489T>A	Y497N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts pathogenic. Based on these concordant predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.393608	Uncertain	0.950	0.181	0.000											-11.884	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	3.64	Destabilizing	0.1	3.97	Destabilizing	3.81	Destabilizing	2.49	Destabilizing	0.870	Likely Pathogenic	-8.85	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.66	Pathogenic	0.01	Affected			0.2114	0.0612		-2	-2	-2.2	-49.07
c.1625A>C	N542T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N542T is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are SIFT and Rosetta. Tools that predict a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. 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											-9.918	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	1.13	Ambiguous	0.1	0.20	Likely Benign	0.67	Ambiguous	0.75	Ambiguous	0.784	Likely Pathogenic	-5.37	Deleterious	0.997	Probably Damaging	0.990	Probably Damaging	-1.41	Pathogenic	0.12	Tolerated			0.1120	0.5872		0	0	2.8	-13.00
c.1756G>C	D586H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586H missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from premPS and SIFT, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all indicate pathogenicity. The high‑accuracy methods reinforce this trend: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, as there is no conflicting status to contradict the prediction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-10.104	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.3	0.89	Ambiguous	0.95	Ambiguous	0.26	Likely Benign	0.672	Likely Pathogenic	-3.44	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.23	Pathogenic	0.17	Tolerated			0.1307	0.5558		1	-1	0.3	22.05
c.1798C>G	P600A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P600A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from Rosetta and premPS, while the remaining 11 tools (REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM Consensus) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports an uncertain result. Taken together, the overwhelming majority of evidence indicates that P600A 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	0.009728	Structured	0.162960	Uncertain	0.947	0.147	0.000											-11.385	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.0	-3.30	Stabilizing	-0.57	Ambiguous	0.39	Likely Benign	0.581	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.38	Pathogenic	0.03	Affected			0.3692	0.4132		1	-1	3.4	-26.04
c.1896C>A	N632K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N632K is not reported in ClinVar and is present in gnomAD. Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classify it as pathogenic; premPS is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the preponderance of evidence points to a pathogenic effect for N632K, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.041437	Uncertain	0.938	0.254	0.000								6-33440948-C-A			-13.266	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	-0.06	Likely Benign	0.2	0.12	Likely Benign	0.03	Likely Benign	0.95	Ambiguous	0.766	Likely Pathogenic	-5.14	Deleterious	0.983	Probably Damaging	0.714	Possibly Damaging	-1.43	Pathogenic	0.01	Affected	3.37	34	0.2375	0.4897		0	1	-0.4	14.07
c.1896C>G	N632K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N632K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the majority of other in‑silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall consensus of the majority of tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.041437	Uncertain	0.938	0.254	0.000											-13.266	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	-0.06	Likely Benign	0.2	0.12	Likely Benign	0.03	Likely Benign	0.95	Ambiguous	0.766	Likely Pathogenic	-5.14	Deleterious	0.983	Probably Damaging	0.714	Possibly Damaging	-1.43	Pathogenic	0.01	Affected	3.37	34	0.2375	0.4897		0	1	-0.4	14.07
c.1967A>C	E656A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E656A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments further reveal that AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus also indicates likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No prediction or stability result is missing or inconclusive. Based on the overall evidence, the variant is most likely pathogenic; this assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-14.373	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.0	0.10	Likely Benign	0.11	Likely Benign	-0.13	Likely Benign	0.499	Likely Benign	-5.38	Deleterious	0.985	Probably Damaging	0.755	Possibly Damaging	3.46	Benign	0.03	Affected			0.4244	0.6271		0	-1	5.3	-58.04
c.2048T>A	I683N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I683N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized returns a pathogenic score, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) also indicates pathogenicity. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.143268	Uncertain	0.848	0.314	0.000											-12.120	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.18	Destabilizing	0.1	2.08	Destabilizing	2.13	Destabilizing	1.46	Destabilizing	0.546	Likely Pathogenic	-6.87	Deleterious	1.000	Probably Damaging	0.992	Probably Damaging	3.26	Benign	0.01	Affected			0.0978	0.1133		-2	-3	-8.0	0.94
c.245T>G	L82R 2D AIThe SynGAP1 missense variant L82R is not 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 (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, and this is not contradicted by any ClinVar annotation. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375											-6.345	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.077	Likely Benign	-2.18	Neutral	0.939	Possibly Damaging	0.114	Benign	3.67	Benign	0.00	Affected			0.1338	0.0590		-3	-2	-8.3	43.03
c.2468G>A	S823N 2D AIThe SynGAP1 missense variant S823N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.880	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-1.76	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1370	0.5172		1	1	-2.7	27.03
c.3527A>T	E1176V 2D AISynGAP1 missense variant E1176V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability approach, has no available result for this variant. Overall, the balance of evidence favors a benign classification, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.572075	Binding	0.525	0.715	0.250											-3.238	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.490	Likely Benign	-2.41	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	5.69	Benign	0.13	Tolerated			0.0452	0.6423		-2	-2	7.7	-29.98
c.394T>A	F132I 2D AISynGAP1 missense variant F132I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign) and Foldetta results are unavailable. Because the majority of consensus tools predict benign and no ClinVar evidence contradicts this, the variant is most likely benign, although the pathogenic signal from AlphaMissense‑Optimized and the inconclusive SGM Consensus leave some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-6.245	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-3.23	Deleterious	0.084	Benign	0.020	Benign	3.36	Benign	0.00	Affected			0.2306	0.1698		1	0	1.7	-34.02
c.3998A>T	E1333V 2D AIThe SynGAP1 E1333V missense change is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs two benign votes), and Foldetta results are unavailable. Overall, the majority of evidence (six pathogenic vs three benign) points to a pathogenic impact. 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.			0.930790	Disordered	0.953319	Binding	0.347	0.746	0.750											-4.322	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.289	Likely Benign	-4.30	Deleterious	0.994	Probably Damaging	0.981	Probably Damaging	2.81	Benign	0.00	Affected			0.0994	0.7615		-2	-2	7.7	-29.98
c.499G>C	D167H 2D AIThe SynGAP1 missense variant D167H is not 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 results are unavailable, so they do not influence the overall assessment. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-12.606	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic										0.338	Likely Benign	-3.29	Deleterious	0.898	Possibly Damaging	0.557	Possibly Damaging	3.93	Benign	0.00	Affected			0.1478	0.7563		1	-1	0.3	22.05
c.529T>G	F177V 2D AIThe SynGAP1 missense variant F177V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of standard predictors favor a benign outcome, but the optimized AlphaMissense model and ESM1b suggest potential pathogenicity. Thus, the variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-11.582	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-1.26	Neutral	0.028	Benign	0.009	Benign	4.18	Benign	0.06	Tolerated			0.2454	0.3526		-1	-1	1.4	-48.04
c.565C>G	P189A 2D AIThe SynGAP1 missense variant P189A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic, two benign), and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) and the pathogenic call from AlphaMissense‑Optimized suggest that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250											-4.998	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-5.46	Deleterious	0.941	Possibly Damaging	0.607	Possibly Damaging	4.07	Benign	0.07	Tolerated			0.3719	0.6209		1	-1	3.4	-26.04
c.620A>C	K207T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K207T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta, Foldetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic; Foldetta’s stability analysis is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K207T, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-11.002	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	2.15	Destabilizing	0.8	0.57	Ambiguous	1.36	Ambiguous	0.78	Ambiguous	0.239	Likely Benign	-4.57	Deleterious	0.982	Probably Damaging	0.747	Possibly Damaging	3.99	Benign	0.07	Tolerated			0.1636	0.4031		0	-1	3.2	-27.07
c.667A>C	T223P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T223P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Uncertain. No other high‑accuracy tools provide a definitive prediction. Overall, the majority of evidence points to a pathogenic impact. 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	PH	0.070400	Structured	0.382605	Uncertain	0.867	0.316	0.125											-13.707	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.3	3.45	Destabilizing	1.94	Ambiguous	0.67	Ambiguous	0.898	Likely Pathogenic	-4.54	Deleterious	0.838	Possibly Damaging	0.367	Benign	5.72	Benign	0.01	Affected			0.1464	0.3728		0	-1	-0.9	-3.99
c.1012G>C	D338H 2D AIThe SynGAP1 missense variant D338H is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to premPS, whereas the remaining 11 tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all classify the variant as pathogenic or likely pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, while Foldetta’s stability analysis is inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for D338H, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.363354	Uncertain	0.460	0.438	0.375											-12.325	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	1.32	Ambiguous	1.2	0.76	Ambiguous	1.04	Ambiguous	0.18	Likely Benign	0.515	Likely Pathogenic	-4.42	Deleterious	0.966	Probably Damaging	0.770	Possibly Damaging	1.71	Pathogenic	0.01	Affected			0.1671	0.6654		1	-1	0.3	22.05
c.1241T>C	M414T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M414T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta; Rosetta remains uncertain. High‑accuracy methods all support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta predicts a destabilizing, pathogenic outcome. Consequently, the consensus of the most reliable predictors classifies M414T as pathogenic, with no conflict with the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000											-8.698	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.04	Destabilizing	0.1	1.96	Ambiguous	2.00	Destabilizing	1.27	Destabilizing	0.406	Likely Benign	-5.00	Deleterious	0.997	Probably Damaging	0.972	Probably Damaging	3.41	Benign	0.08	Tolerated			0.1771	0.1976		-1	-1	-2.6	-30.09
c.1247T>C	L416P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from the remaining 13 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen2_HumDiv, polyPhen2_HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and the SGM Consensus). High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions are inconclusive. Based on the overall consensus of the majority of tools and the high‑accuracy methods, the variant is most likely pathogenic, which is consistent with the lack of ClinVar reporting and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.859	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.59	Destabilizing	0.1	6.23	Destabilizing	4.41	Destabilizing	1.27	Destabilizing	0.284	Likely Benign	-3.56	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.35	Benign	0.21	Tolerated			0.3589	0.1353		-3	-3	-5.4	-16.04
c.1261G>A	A421T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421T is not reported in ClinVar and is present in gnomAD (ID 6‑33438166‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of consensus predictions lean toward a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000								6-33438166-G-A	1	6.19e-7	-9.217	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.75	Ambiguous	0.2	0.18	Likely Benign	0.47	Likely Benign	0.99	Ambiguous	0.179	Likely Benign	-3.12	Deleterious	0.353	Benign	0.136	Benign	3.43	Benign	0.09	Tolerated	3.37	29	0.1346	0.4439		0	1	-2.5	30.03
c.132G>C	W44C 2D AIThe SynGAP1 missense variant W44C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because the variant has not yet been classified in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.301917	Structured	0.431379	Uncertain	0.377	0.748	0.375											-6.216	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.321	Likely Benign	-4.70	Deleterious	0.943	Possibly Damaging	0.941	Probably Damaging	3.14	Benign	0.00	Affected			0.3542	0.2370		-8	-2	3.4	-83.07
c.132G>T	W44C 2D AIThe SynGAP1 missense variant W44C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (seven pathogenic vs. three benign) indicate a pathogenic effect. This prediction is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.301917	Structured	0.431379	Uncertain	0.377	0.748	0.375											-6.216	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.321	Likely Benign	-4.70	Deleterious	0.943	Possibly Damaging	0.941	Probably Damaging	3.14	Benign	0.00	Affected			0.3542	0.2370		-8	-2	3.4	-83.07
c.1354G>T	V452F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V452F variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect are Rosetta and FATHMM, whereas the remaining tools (REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. Based on the preponderance of evidence, the variant is most likely pathogenic, a conclusion that contradicts its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000					Uncertain		1				-14.769	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	9.21	Destabilizing	0.1	0.37	Likely Benign	4.79	Destabilizing	0.61	Ambiguous	0.511	Likely Pathogenic	-4.94	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.29	Benign	0.00	Affected	3.37	34	0.0564	0.3451		-1	-1	-1.4	48.04	249.4	-35.7	0.0	0.0	0.4	0.1							X	Potentially Pathogenic	The iso-propyl side chain of Val452, located in the middle of an α helix (res. Val441-Ser457), packs against hydrophobic residues in the inter-helix space at the intersection of three α helices (e.g., Leu500, His453, Leu465). In the variant simulations, the larger side chain of Phe452 cannot pack against the opposing α helix (res. Leu489-Glu519) as efficiently as valine. Due to space restrictions, the phenol ring adjusts to make room by rotating slightly sideways in the inter-helix space. Besides this small and local shift, no large-scale effects on the protein structure are seen based on the simulations. However, the size difference between the swapped residues could affect the protein folding process.
c.1756G>T	D586Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that indicate a benign effect include FoldX, SIFT, and premPS, whereas the majority of other in silico predictors (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic outcome. Rosetta and Foldetta, which assess protein‑folding stability, return uncertain results and are therefore not considered evidence for either direction. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as pathogenic, and Foldetta as uncertain. Overall, the preponderance of pathogenic predictions (13 vs. 3 benign) suggests that D586Y 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	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-12.916	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.4	1.09	Ambiguous	0.73	Ambiguous	-0.49	Likely Benign	0.712	Likely Pathogenic	-5.38	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.16	Pathogenic	0.41	Tolerated			0.0623	0.5634		-4	-3	2.2	48.09
c.1856C>T	T619I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T619I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity unanimously classify the variant as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect; the remaining tools (FoldX, Rosetta, Foldetta, premPS) return uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Based on the consensus of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.219301	Structured	0.119723	Uncertain	0.929	0.237	0.000											-11.760	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	-1.06	Ambiguous	0.1	-1.35	Ambiguous	-1.21	Ambiguous	0.58	Ambiguous	0.735	Likely Pathogenic	-5.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.40	Pathogenic	0.03	Affected			0.0869	0.4377		0	-1	5.2	12.05
c.1906T>G	F636V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F636V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000											-14.603	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.1	5.13	Destabilizing	4.10	Destabilizing	1.07	Destabilizing	0.533	Likely Pathogenic	-6.74	Deleterious	0.991	Probably Damaging	0.985	Probably Damaging	3.44	Benign	0.04	Affected			0.1841	0.2030		-1	-1	1.4	-48.04
c.262G>C	V88L 2D AIThe SynGAP1 V88L variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of tools suggest a benign impact, but the high‑accuracy predictions are conflicting. The variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-5.808	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.066	Likely Benign	-0.79	Neutral	0.225	Benign	0.027	Benign	3.74	Benign	0.00	Affected			0.1457	0.4562		2	1	-0.4	14.03
c.262G>T	V88L 2D AIThe SynGAP1 missense variant V88L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM, whereas SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect; a Foldetta stability analysis is unavailable. Overall, the majority of 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 the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500											-5.808	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.066	Likely Benign	-0.79	Neutral	0.225	Benign	0.027	Benign	3.74	Benign	0.00	Affected			0.1457	0.4562		2	1	-0.4	14.03
c.3493T>C	S1165P 2D AIThe SynGAP1 missense variant S1165P is not reported in ClinVar and has no entry in gnomAD. 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, whereas the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of tools (six benign vs. four pathogenic) indicate that the variant is most likely benign. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.835017	Binding	0.308	0.807	0.375											-3.476	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.147	Likely Benign	-1.87	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.55	Benign	0.23	Tolerated			0.2295	0.4930		1	-1	-0.8	10.04
c.3506A>T	E1169V 2D AIThe SynGAP1 E1169V missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic signal: AlphaMissense‑Optimized is pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive (2 pathogenic vs 2 benign), and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence (seven pathogenic vs three benign predictions) indicates that E1169V is most likely pathogenic. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625											-2.482	Likely Benign	0.975	Likely Pathogenic	Likely Pathogenic										0.227	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.51	Benign	0.00	Affected			0.0581	0.7028		-2	-2	7.7	-29.98
c.3809A>C	E1270A 2D AIThe SynGAP1 missense change E1270A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL is the only score that flags the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM‑Consensus also indicates a likely pathogenic outcome. No Foldetta (FoldX‑MD/Rosetta stability) result is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a pathogenic impact for E1270A, and this conclusion is consistent with the absence of a ClinVar entry (i.e., no contradictory clinical classification). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-12.081	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic										0.388	Likely Benign	-5.04	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.3024	0.5126		0	-1	5.3	-58.04
c.482C>T	P161L 2D AIThe SynGAP1 missense variant P161L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized also predicts Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of predictions (seven pathogenic vs. four benign) indicate that P161L 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		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-12.159	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic										0.236	Likely Benign	-4.48	Deleterious	0.001	Benign	0.003	Benign	3.92	Benign	0.00	Affected			0.2424	0.5902		-3	-3	5.4	16.04
c.683C>A	T228K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T228K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, and FATHMM, whereas 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 give uncertain results (Rosetta and premPS). High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict any existing ClinVar annotation because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125											-9.143	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.03	Likely Benign	0.1	0.87	Ambiguous	0.45	Likely Benign	0.70	Ambiguous	0.676	Likely Pathogenic	-3.00	Deleterious	0.906	Possibly Damaging	0.521	Possibly Damaging	5.60	Benign	0.02	Affected			0.1322	0.3590		0	-1	-3.2	27.07
c.728T>G	I243S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I243S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity largely agree: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. Only FATHMM predicts a benign outcome. High‑accuracy methods reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. No predictions are missing or inconclusive. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.363090	Structured	0.344471	Uncertain	0.842	0.347	0.000											-14.097	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.52	Destabilizing	0.2	2.22	Destabilizing	2.37	Destabilizing	1.71	Destabilizing	0.802	Likely Pathogenic	-3.55	Deleterious	0.995	Probably Damaging	0.795	Possibly Damaging	5.52	Benign	0.00	Affected			0.2658	0.0600		-1	-2	-5.3	-26.08
c.983A>G	Y328C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y328C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions are absent; all evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the substitution as pathogenic. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely pathogenic verdict, and Foldetta (integrating FoldX‑MD and Rosetta outputs) also reports a pathogenic outcome. Consequently, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.411940	Structured	0.392519	Uncertain	0.916	0.497	0.000											-12.385	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	2.52	Destabilizing	0.1	3.74	Destabilizing	3.13	Destabilizing	1.40	Destabilizing	0.523	Likely Pathogenic	-8.01	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.55	Pathogenic	0.01	Affected			0.3154	0.2882		0	-2	3.8	-60.04
c.1016A>T	K339M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339M missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX and premPS, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools with uncertain or inconclusive results are Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K339M. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-13.387	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.23	Likely Benign	0.0	0.88	Ambiguous	0.56	Ambiguous	-0.37	Likely Benign	0.575	Likely Pathogenic	-4.95	Deleterious	0.999	Probably Damaging	0.964	Probably Damaging	1.92	Pathogenic	0.01	Affected			0.0967	0.3541		0	-1	5.8	3.02
c.1282T>A	Y428N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, which classifies the change as benign. All other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-12.164	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	2.34	Destabilizing	0.0	3.81	Destabilizing	3.08	Destabilizing	1.85	Destabilizing	0.533	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.03	Affected			0.2607	0.0971		-2	-2	-2.2	-49.07
c.1326A>C	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1326A>T	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1370G>T	S457I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S457I lies within the GAP domain. ClinVar has no entry for this change, and it is absent from gnomAD. Prediction tools that report a benign effect include FoldX and FATHMM, whereas the majority of other in silico predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default and AlphaMissense‑Optimized—classify it as pathogenic. Uncertain results come from Rosetta, Foldetta and premPS. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN) is Likely Pathogenic, and Foldetta remains inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-13.170	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	-0.26	Likely Benign	0.3	-0.96	Ambiguous	-0.61	Ambiguous	0.65	Ambiguous	0.557	Likely Pathogenic	-5.73	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.34	Benign	0.02	Affected			0.0779	0.6095		-1	-2	5.3	26.08
c.1409T>C	M470T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M470T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy methods further support this: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or folding‑stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.351497	Uncertain	0.908	0.272	0.000					Uncertain		1				-8.104	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	3.19	Destabilizing	0.1	2.68	Destabilizing	2.94	Destabilizing	1.49	Destabilizing	0.763	Likely Pathogenic	-5.30	Deleterious	0.996	Probably Damaging	0.985	Probably Damaging	-1.08	Pathogenic	0.24	Tolerated	3.37	34	0.1782	0.1950		-1	-1	-2.6	-30.09	213.8	46.5	0.0	0.0	-0.2	0.2		X					X	Potentially Pathogenic	The thioether group of Met470, located in the middle of an α helix (res. Ala461–Phe476), interacts with hydrophobic residues in the inter-helix space (e.g., Val473, Leu558, Cys576, Trp572) formed by two other α helices (res. Ser604–Arg581, res. Pro562–Arg579). In the WT simulations, the Met470 side chain also packs against the positively charged guanidinium groups of Arg575, Arg429, and Arg579, which form salt bridges with the negatively charged carboxylate groups of the Asp474 and Asp467 side chains at the protein surface. In the variant simulations, the hydroxyl group of the Thr470 side chain forms an H-bond with the backbone carbonyl group of Ser466 in the α helix, potentially lowering its structural integrity. Importantly, the hydroxyl group of Thr470 also forms an H-bond with the guanidinium group of Arg575, which helps it form a more permanent salt bridge with Asp467.
c.1445T>G	L482R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while FoldX, Rosetta, and Foldetta return uncertain results. In a consensus framework, the SGM‑Consensus score is “Likely Pathogenic,” reflecting the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus is Likely Pathogenic, and Foldetta remains inconclusive. Taken together, the overwhelming majority of evidence points to a pathogenic effect. Thus, 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	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-14.684	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.74	Ambiguous	0.1	1.31	Ambiguous	1.03	Ambiguous	1.53	Destabilizing	0.878	Likely Pathogenic	-5.92	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	-1.27	Pathogenic	0.01	Affected			0.1255	0.0679		-3	-2	-8.3	43.03
c.1453C>T	R485C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R485C (gnomAD ID 6‑33438485‑C‑T) is listed in ClinVar with an uncertain significance. Functional prediction tools largely disagree: benign calls come from Rosetta and premPS, whereas pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus is labeled likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. With the majority of evidence pointing to pathogenicity and no contradictory data from ClinVar, the variant is most likely pathogenic, although ClinVar has not yet reached a definitive 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					Uncertain		2	6-33438485-C-T	9	5.58e-6	-14.294	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	0.26	Likely Benign	0.63	Ambiguous	0.44	Likely Benign	0.597	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.90	Pathogenic	0.00	Affected	3.37	35	0.3350	0.2762		-4	-3	7.0	-53.05	225.5	99.6	-0.1	0.0	-0.3	0.2				X				Uncertain	The guanidinium group of Arg485 is located in a short helical structure (res. Glu480-Leu482) within an α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. The side chain of Arg485 acts as the “arginine finger” of SynGAP, playing a crucial role in Ras-GTPase activation. Consequently, the residue swap inhibits the conversion of GTP to GDP at the enzyme’s active site. Although no negative effects on the protein structure are observed during the simulations, no definite conclusions can be drawn due to the critical role of Arg485 in GTPase activation.
c.1616A>T	H539L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H539L is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is pathogenic, the SGM Consensus is likely pathogenic, and Foldetta’s stability prediction is uncertain. No evidence from the available data contradicts the ClinVar status, which is currently unreported. Overall, the preponderance of computational evidence indicates that H539L is most likely pathogenic. 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											-14.161	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	-1.76	Ambiguous	0.1	-0.17	Likely Benign	-0.97	Ambiguous	0.35	Likely Benign	0.879	Likely Pathogenic	-10.17	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.29	Pathogenic	0.01	Affected			0.0758	0.3680		-2	-3	7.0	-23.98
c.1726T>G	C576G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C576G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from REVEL, FoldX (uncertain), Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a benign outcome. When high‑accuracy methods are considered, AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) also predicts pathogenicity. No prediction is inconclusive or missing. Consequently, the variant is most likely pathogenic based on the consensus of available computational evidence, and this assessment does not contradict any ClinVar annotation (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.017684	Uncertain	0.913	0.245	0.000											-14.809	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.66	Ambiguous	0.0	2.53	Destabilizing	2.10	Destabilizing	1.67	Destabilizing	0.586	Likely Pathogenic	-10.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.00	Affected			0.3269	0.2574		-3	-3	-2.9	-46.09
c.1808T>C	M603T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M603T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that provide a clear verdict all classify the substitution as pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool in the dataset reports a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus indicates likely pathogenic, while the Foldetta stability analysis is inconclusive and therefore not considered evidence. No contradictory evidence is present in ClinVar. Consequently, the variant is most likely pathogenic based on the available predictions, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000											-13.152	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.71	Ambiguous	0.2	1.71	Ambiguous	1.71	Ambiguous	0.66	Ambiguous	0.903	Likely Pathogenic	-5.48	Deleterious	0.996	Probably Damaging	0.985	Probably Damaging	-1.29	Pathogenic	0.00	Affected			0.1883	0.1495		-1	-1	-2.6	-30.09
c.1817G>T	S606I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, premPS, and FATHMM, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic impact for S606I. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-14.552	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	-0.60	Ambiguous	0.1	-0.08	Likely Benign	-0.34	Likely Benign	0.41	Likely Benign	0.288	Likely Benign	-5.98	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.31	Benign	0.01	Affected			0.0891	0.4162		-1	-2	5.3	26.08
c.2453C>G	P818R 2D AIThe SynGAP1 missense variant P818R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. ESM1b is uncertain and does not contribute to a consensus. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Pathogenic” designation. AlphaMissense‑Optimized independently predicts pathogenicity, while Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-7.267	In-Between	0.976	Likely Pathogenic	Likely Pathogenic										0.374	Likely Benign	-5.12	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	1.97	Pathogenic	0.03	Affected			0.1499	0.4547		0	-2	-2.9	59.07
c.2522T>A	V841E 2D AIThe SynGAP1 missense variant V841E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction tools and high‑accuracy methods indicates that V841E is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125											-13.750	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.292	Likely Benign	-3.13	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.52	Benign	0.00	Affected			0.0939	0.1656		-2	-2	-7.7	29.98
c.2617A>C	S873R 2D AIThe SynGAP1 missense variant S873R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. 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 ClinVar annotation because the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-5.856	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.218	Likely Benign	-2.74	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.67	Benign	0.06	Tolerated	3.77	5	0.0970	0.3667		0	-1	-3.7	69.11
c.2619C>A	S873R 2D AIThe SynGAP1 missense variant S873R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the balance of evidence (five pathogenic vs. four benign predictions, with a pathogenic high‑accuracy tool) suggests the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-5.856	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-2.74	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.67	Benign	0.06	Tolerated	3.77	5	0.0970	0.3667		0	-1	-3.7	69.11
c.2619C>G	S873R 2D AIThe SynGAP1 missense variant S873R is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33443171‑C‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic versus two benign votes), and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors 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.			0.414856	Structured	0.649816	Binding	0.283	0.866	0.125					Uncertain		1	6-33443171-C-G	1	6.20e-7	-5.856	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-2.74	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.67	Benign	0.06	Tolerated	3.77	5	0.0970	0.3667		0	-1	-3.7	69.11
c.2794T>G	F932V 2D AIThe SynGAP1 missense variant F932V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-5.728	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.392	Likely Benign	-3.68	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.32	Pathogenic	0.01	Affected			0.2137	0.3082		-1	-1	1.4	-48.04
c.3476C>T	S1159F 2D AIThe SynGAP1 missense variant S1159F 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 the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains benign; Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-5.627	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.11	Neutral	0.997	Probably Damaging	0.996	Probably Damaging	2.66	Benign	0.20	Tolerated			0.0527	0.5211		-3	-2	3.6	60.10
c.3539T>A	L1180H 2D AIThe SynGAP1 missense variant L1180H is not reported in ClinVar and has no gnomAD allele, so its population frequency is unknown. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments highlight AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus leans benign; Foldetta results are not available. Overall, five of nine individual predictors favor pathogenicity, four favor benign, and the consensus tool suggests benign. Thus, the variant is most likely pathogenic based on the preponderance of high‑confidence predictions, and this assessment is not contradicted by ClinVar, which contains no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-5.621	Likely Benign	0.976	Likely Pathogenic	Likely Pathogenic										0.213	Likely Benign	-0.22	Neutral	0.987	Probably Damaging	0.865	Possibly Damaging	2.65	Benign	0.00	Affected			0.0991	0.0860		-2	-3	-7.0	23.98
c.3597G>C	E1199D 2D AIThe SynGAP1 missense variant E1199D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-10.917	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.234	Likely Benign	-2.08	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.52	Benign	0.00	Affected			0.1728	0.2146		3	2	0.0	-14.03
c.3597G>T	E1199D 2D AIThe SynGAP1 missense variant E1199D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.538167	Disordered	0.444533	Uncertain	0.878	0.598	0.250											-10.917	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.236	Likely Benign	-2.08	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.52	Benign	0.00	Affected			0.1728	0.2146		3	2	0.0	-14.03
c.3749A>C	Q1250P 2D AIThe SynGAP1 missense variant Q1250P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic. No Foldetta stability prediction is available for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750											-10.383	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.085	Likely Benign	-3.12	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	2.62	Benign	0.02	Affected			0.2376	0.4149		0	-1	1.9	-31.01
c.404G>C	R135P 2D AIThe SynGAP1 missense variant R135P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. In silico predictors that classify the variant as benign include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy tools give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this assessment is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-9.512	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.139	Likely Benign	-3.19	Deleterious	0.609	Possibly Damaging	0.308	Benign	3.68	Benign	0.01	Affected			0.2052	0.4535		0	-2	2.9	-59.07
c.404G>T	R135L 2D AIThe SynGAP1 missense variant R135L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized predicts pathogenicity. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy tools, support a pathogenic classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.676514	Binding	0.380	0.898	0.250											-7.372	In-Between	0.976	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-3.61	Deleterious	0.308	Benign	0.122	Benign	3.70	Benign	0.01	Affected			0.1962	0.4727		-3	-2	8.3	-43.03
c.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	-3.11	Deleterious	0.392	Benign	0.230	Benign	3.60	Benign	0.00	Affected			0.1934	0.4627		1	-1	-0.8	10.04
c.437C>T	S146L 2D AIThe SynGAP1 missense variant S146L is not 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. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) which 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 majority of predictions indicate a pathogenic impact, and this is consistent with the lack of ClinVar annotation—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625											-15.179	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.130	Likely Benign	-3.77	Deleterious	0.084	Benign	0.063	Benign	3.63	Benign	0.00	Affected			0.0856	0.4975		-3	-2	4.6	26.08
c.499G>T	D167Y 2D AIThe SynGAP1 missense variant D167Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and FATHMM, whereas the remaining eight predictors—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 indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a pathogenic impact for D167Y, and this conclusion is not contradicted by any ClinVar annotation, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.502306	Binding	0.377	0.667	0.375											-14.228	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic										0.414	Likely Benign	-4.23	Deleterious	0.898	Possibly Damaging	0.557	Possibly Damaging	3.90	Benign	0.00	Affected			0.0493	0.6358		-4	-3	2.2	48.09
c.626T>C	V209A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V209A is reported in gnomAD (ID 6‑33435268‑T‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL and FATHMM. In contrast, a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Stability‑based methods FoldX, Rosetta, and the combined Foldetta score are uncertain and therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that V209A is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.247041	Structured	0.397624	Uncertain	0.874	0.331	0.125								6-33435268-T-C	1	6.20e-7	-9.796	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.56	Ambiguous	0.3	1.85	Ambiguous	1.71	Ambiguous	1.60	Destabilizing	0.236	Likely Benign	-2.79	Deleterious	0.958	Probably Damaging	0.581	Possibly Damaging	3.70	Benign	0.02	Affected	3.41	13	0.2237	0.1919		0	0	-2.4	-28.05
c.721A>C	K241Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K241Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, FATHMM, and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, nine tools predict pathogenicity versus four predicting benign, with no ClinVar evidence to contradict these findings. Thus, the variant is most likely pathogenic. 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											-10.593	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.33	Likely Benign	0.0	0.46	Likely Benign	0.40	Likely Benign	0.63	Ambiguous	0.767	Likely Pathogenic	-3.33	Deleterious	0.995	Probably Damaging	0.914	Probably Damaging	5.83	Benign	0.04	Affected			0.4225	0.1527		1	1	0.4	-0.04
c.795G>C	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, whereas the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this 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	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.350	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.795G>T	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, while the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain or inconclusive results are reported only for FoldX, Foldetta, and premPS, and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this 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 Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.351	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
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	1.52	Ambiguous	0.1	2.15	Destabilizing	1.84	Ambiguous	0.91	Ambiguous	0.379	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.60	Pathogenic	0.02	Affected			0.1908	0.2540		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	1.52	Ambiguous	0.1	2.15	Destabilizing	1.84	Ambiguous	0.91	Ambiguous	0.383	Likely Benign	-2.76	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.60	Pathogenic	0.02	Affected			0.1908	0.2540		3	2	0.0	-14.03
c.931C>G	H311D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H311D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess evolutionary conservation and protein function uniformly indicate a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as pathogenic. The majority‑vote consensus (SGM‑Consensus) also reports it as likely pathogenic. Tools that evaluate structural stability give inconclusive results: FoldX, Rosetta, Foldetta, and premPS are listed as uncertain. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (derived from the same set of predictors) reports likely pathogenic, while Foldetta’s combined FoldX‑MD/Rosetta stability analysis remains uncertain. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect, which is consistent with the absence of a benign ClinVar annotation and the lack of population frequency data. 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											-13.513	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.27	Ambiguous	0.0	1.83	Ambiguous	1.55	Ambiguous	0.89	Ambiguous	0.633	Likely Pathogenic	-6.94	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.94	Pathogenic	0.02	Affected			0.2301	0.2008		1	-1	-0.3	-22.05
c.953C>A	P318Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity. Only FoldX, Rosetta, and Foldetta provide uncertain results and are therefore not considered evidence for benign impact. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Consequently, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000											-11.403	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	1.64	Ambiguous	0.2	1.29	Ambiguous	1.47	Ambiguous	1.18	Destabilizing	0.638	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.83	Pathogenic	0.01	Affected			0.1467	0.4731		0	-1	-1.9	31.01
c.978T>A	H326Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and SIFT, whereas a majority of tools predict a pathogenic outcome: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools, Foldetta (combining FoldX‑MD and Rosetta) and Rosetta alone, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for H326Q. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-8.688	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.1	1.67	Ambiguous	1.07	Ambiguous	1.00	Destabilizing	0.444	Likely Benign	-6.89	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.07	Pathogenic	0.10	Tolerated			0.1485	0.3500		3	0	-0.3	-9.01
c.978T>G	H326Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H326Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and SIFT, whereas a majority of tools predict a pathogenic outcome: premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools, Foldetta (combining FoldX‑MD and Rosetta) and Rosetta alone, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus also indicates likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence from multiple independent predictors points to a pathogenic effect for H326Q. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.342579	Structured	0.418150	Uncertain	0.944	0.455	0.000											-8.688	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.1	1.67	Ambiguous	1.07	Ambiguous	1.00	Destabilizing	0.444	Likely Benign	-6.89	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.07	Pathogenic	0.10	Tolerated			0.1485	0.3500		3	0	-0.3	-9.01
c.1073T>C	F358S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358S variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of algorithms predict a pathogenic outcome: FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Rosetta’s assessment is uncertain and is not taken as evidence. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the preponderance of pathogenic predictions and the agreement of the high‑accuracy tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-9.316	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.32	Destabilizing	0.2	1.97	Ambiguous	2.15	Destabilizing	1.14	Destabilizing	0.493	Likely Benign	-6.48	Deleterious	0.998	Probably Damaging	0.986	Probably Damaging	4.07	Benign	0.20	Tolerated			0.3891	0.1333		-3	-2	-3.6	-60.10
c.1085G>T	W362L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362L is not reported in ClinVar and is absent from gnomAD. All tools except premPS predict pathogenic, leaving no benign predictions. Functional prediction tools uniformly indicate a deleterious effect: SGM‑Consensus, 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. High‑accuracy methods corroborate this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Consequently, the variant is most likely pathogenic, and this prediction 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	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-12.748	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.16	Destabilizing	0.1	2.60	Destabilizing	2.38	Destabilizing	0.71	Ambiguous	0.523	Likely Pathogenic	-11.95	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.32	Pathogenic	0.01	Affected			0.2701	0.2452		-2	-2	4.7	-73.05
c.1213C>A	R405S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R405S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM‑Consensus itself is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts Pathogenic. Taken together, the overwhelming majority of evidence indicates that R405S 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	0.250310	Structured	0.404888	Uncertain	0.949	0.315	0.000											-11.326	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.66	Destabilizing	0.5	2.08	Destabilizing	2.37	Destabilizing	1.22	Destabilizing	0.405	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.67	Benign	0.05	Affected			0.2829	0.4646		0	-1	3.7	-69.11
c.1217A>C	Y406S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FoldX, Rosetta, premPS, and Foldetta all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-12.014	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	3.51	Destabilizing	0.3	4.08	Destabilizing	3.80	Destabilizing	1.40	Destabilizing	0.190	Likely Benign	-6.72	Deleterious	0.991	Probably Damaging	0.886	Possibly Damaging	3.80	Benign	0.06	Tolerated			0.4719	0.2817		-3	-2	0.5	-76.10
c.1231A>T	I411F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411F is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction is missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000											-13.377	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	5.71	Destabilizing	0.1	4.53	Destabilizing	5.12	Destabilizing	0.73	Ambiguous	0.503	Likely Pathogenic	-3.69	Deleterious	0.998	Probably Damaging	0.973	Probably Damaging	3.30	Benign	0.00	Affected			0.0538	0.2853		1	0	-1.7	34.02
c.1244A>G	E415G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E415G 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. Tools that predict a pathogenic effect comprise 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‑based methods (FoldX, Rosetta, premPS) and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for E415G. This prediction is consistent with the lack of ClinVar annotation and does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.330366	Uncertain	0.915	0.236	0.000											-12.244	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.16	Ambiguous	0.2	0.88	Ambiguous	1.02	Ambiguous	0.65	Ambiguous	0.432	Likely Benign	-6.45	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.20	Benign	0.01	Affected			0.2518	0.3158		0	-2	3.1	-72.06
c.1381G>C	A461P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A461P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and FATHMM, whereas the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS remains uncertain. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is pathogenic. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-13.869	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	-0.35	Likely Benign	0.1	5.09	Destabilizing	2.37	Destabilizing	0.84	Ambiguous	0.451	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.849	Possibly Damaging	3.32	Benign	0.03	Affected			0.1748	0.3949		1	-1	-3.4	26.04
c.147C>G	C49W 2D AIThe SynGAP1 missense variant C49W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic and the SGM‑Consensus is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that C49W 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		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-12.247	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.291	Likely Benign	-3.56	Deleterious	0.880	Possibly Damaging	0.914	Probably Damaging	3.83	Benign	0.00	Affected			0.1380	0.3172		-8	-2	-3.4	83.07
c.1574A>C	E525A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E525A is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, premPS, and FATHMM, whereas the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, whereas Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign impact. Overall, the preponderance of evidence from both general and high‑accuracy tools points to a pathogenic classification for E525A, 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	0.206376	Structured	0.023618	Uncertain	0.937	0.382	0.125											-12.627	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.23	Ambiguous	0.6	-0.62	Ambiguous	0.31	Likely Benign	0.09	Likely Benign	0.680	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.68	Benign	0.00	Affected			0.3554	0.3960		0	-1	5.3	-58.04
c.1636T>G	C546G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant C546G is not reported in ClinVar and is present in gnomAD (ID 6‑33438879‑T‑G). Prediction tools that indicate a benign effect include only SIFT, whereas the remaining tools—REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta is inconclusive and therefore not considered evidence. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.009041	Uncertain	0.960	0.288	0.000								6-33438879-T-G	1	6.20e-7	-14.026	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.55	Ambiguous	0.0	2.43	Destabilizing	1.99	Ambiguous	1.53	Destabilizing	0.877	Likely Pathogenic	-9.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.26	Pathogenic	0.06	Tolerated	3.37	35	0.3135	0.2513		-3	-3	-2.9	-46.09
c.1738G>C	G580R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, 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 outcome. No tool predicts a benign effect. Several methods return uncertain results—Rosetta, Foldetta (combining FoldX‑MD and Rosetta outputs), and premPS—so these do not influence the overall assessment. High‑accuracy evaluations reinforce the pathogenic prediction: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains uncertain. Based on the collective evidence, 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	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000											-11.459	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.20	Destabilizing	0.1	1.26	Ambiguous	1.73	Ambiguous	0.81	Ambiguous	0.623	Likely Pathogenic	-7.33	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.26	Pathogenic	0.03	Affected			0.1009	0.3197		-3	-2	-4.1	99.14
c.1757A>T	D586V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D586V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and SIFT. Tools that predict pathogenicity include SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (nine pathogenic vs. five benign) indicate a pathogenic effect. 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.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000											-12.409	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.2	0.03	Likely Benign	0.22	Likely Benign	0.18	Likely Benign	0.801	Likely Pathogenic	-5.58	Deleterious	0.998	Probably Damaging	0.999	Probably Damaging	-1.23	Pathogenic	0.24	Tolerated			0.0826	0.5458		-2	-3	7.7	-15.96
c.176T>A	L59Q 2D AIThe SynGAP1 missense variant L59Q is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools are mixed: benign calls come from SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. No Foldetta stability analysis is available for this residue. Overall, the majority of high‑confidence tools lean toward a pathogenic interpretation, but the presence of several strong benign predictions and the lack of ClinVar evidence suggest uncertainty. The variant is most likely pathogenic based on the prevailing predictions, and this does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-3.841	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.287	Likely Benign	-2.21	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.26	Benign	0.00	Affected			0.1103	0.0758		-2	-2	-7.3	14.97
c.2150T>A	L717H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L717H occurs in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM; all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overwhelming majority of computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-11.107	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	2.27	Destabilizing	0.1	2.04	Destabilizing	2.16	Destabilizing	1.05	Destabilizing	0.317	Likely Benign	-5.23	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.29	Benign	0.00	Affected			0.0918	0.0558		-2	-3	-7.0	23.98
c.2171C>A	A724D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A724D is not reported in ClinVar or gnomAD. Prediction tools that indicate a benign effect include REVEL, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Four methods (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for A724D, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.476583	Structured	0.458050	Uncertain	0.923	0.483	0.250											-12.233	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	1.06	Ambiguous	0.2	0.86	Ambiguous	0.96	Ambiguous	0.60	Ambiguous	0.335	Likely Benign	-4.44	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1596	0.1812		0	-2	-5.3	44.01
c.2465C>A	T822K 2D AIThe SynGAP1 missense variant T822K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of conventional tools lean toward a benign interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction contradicts this. Because ClinVar has no entry for this variant, there is no existing clinical classification to conflict with; thus, the variant is most likely benign based on the preponderance of evidence, though high‑accuracy predictions remain inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750											-1.814	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.215	Likely Benign	-2.25	Neutral	1.000	Probably Damaging	0.988	Probably Damaging	2.51	Benign	0.07	Tolerated			0.1369	0.3552		0	-1	-3.2	27.07
c.2537T>C	L846S 2D AIThe SynGAP1 missense variant L846S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with a likely pathogenic classification. Foldetta predictions are unavailable. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.944	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-3.44	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.25	Pathogenic	0.00	Affected			0.3128	0.1070		-3	-2	-4.6	-26.08
c.3485C>G	P1162R 2D AIThe SynGAP1 missense variant P1162R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs 4 benign) and the pathogenic call from AlphaMissense‑Optimized suggest the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375											-2.657	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.208	Likely Benign	-2.68	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.14	Tolerated			0.1269	0.3439		0	-2	-2.9	59.07
c.3731G>T	S1244I 2D AIThe SynGAP1 missense variant S1244I is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-13.073	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.284	Likely Benign	-4.39	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.08	Pathogenic	0.02	Affected			0.0780	0.4684		-1	-2	5.3	26.08
c.3805G>A	V1269M 2D AIThe SynGAP1 missense variant V1269M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for V1269M, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.787464	Binding	0.843	0.647	0.125											-3.743	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.300	Likely Benign	-2.53	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0582	0.3676		2	1	-2.3	32.06
c.4006G>A	E1336K 2D AIThe SynGAP1 missense variant E1336K is listed in ClinVar (ID 984837) with an “Uncertain” status and is present in gnomAD (6‑33451880‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, 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 likely benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign effect, and this conclusion 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		0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750					Conflicting		3	6-33451880-G-A	6	4.20e-6	-4.697	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic										0.272	Likely Benign	-2.44	Neutral	0.748	Possibly Damaging	0.079	Benign	3.23	Benign	0.00	Affected	3.77	5	0.2630	0.7501		0	1	-0.4	-0.94
c.419C>G	S140C 2D AIThe SynGAP1 missense variant S140C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the S140C variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.587898	Binding	0.321	0.896	0.625											-10.103	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic										0.170	Likely Benign	-3.11	Deleterious	0.999	Probably Damaging	0.990	Probably Damaging	3.49	Benign	0.01	Affected			0.0811	0.5709		0	-1	3.3	16.06
c.469C>A	R157S 2D AIThe SynGAP1 R157S missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic majority vote (2 pathogenic, 1 benign, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that R157S is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.483068	Structured	0.523978	Binding	0.306	0.777	0.375											-7.573	In-Between	0.977	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-2.82	Deleterious	0.993	Probably Damaging	0.982	Probably Damaging	3.85	Benign	0.00	Affected			0.3484	0.2563		0	-1	3.7	-69.11
c.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	-4.22	Deleterious	0.964	Probably Damaging	0.650	Possibly Damaging	3.89	Benign	0.00	Affected			0.2060	0.4039		0	-2	-1.6	40.02
c.620A>T	K207M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K207M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact; premPS is uncertain. High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.596	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	-0.22	Likely Benign	0.0	-0.47	Likely Benign	-0.35	Likely Benign	0.59	Ambiguous	0.336	Likely Benign	-4.67	Deleterious	0.985	Probably Damaging	0.832	Possibly Damaging	3.94	Benign	0.03	Affected			0.0982	0.4705		0	-1	5.8	3.02
c.694G>C	A232P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A232P is 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 FATHMM. Tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from Rosetta, premPS, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome, and Foldetta remains uncertain. Overall, the majority of evaluated tools predict a pathogenic impact, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.307228	Uncertain	0.878	0.305	0.000											-12.697	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.8	1.25	Ambiguous	0.65	Ambiguous	0.71	Ambiguous	0.748	Likely Pathogenic	-2.75	Deleterious	0.917	Possibly Damaging	0.502	Possibly Damaging	5.78	Benign	0.06	Tolerated			0.2163	0.5259		1	-1	-3.4	26.04
c.704C>A	S235Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S235Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include FATHMM and Rosetta, whereas the majority of other in silico predictors (REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the variant as pathogenic. Two tools give inconclusive results: Foldetta (protein‑folding stability) and premPS. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic,” and Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for S235Y, and this conclusion is not contradicted by any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.250310	Structured	0.319150	Uncertain	0.743	0.331	0.000											-15.842	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	3.53	Destabilizing	1.8	0.43	Likely Benign	1.98	Ambiguous	0.66	Ambiguous	0.887	Likely Pathogenic	-5.14	Deleterious	0.971	Probably Damaging	0.641	Possibly Damaging	5.45	Benign	0.00	Affected			0.0733	0.5269		-3	-2	-0.5	76.10
c.754C>G	P252A 2D 3DClick to see structure in 3D Viewer AISynGAP1 P252A is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: a single benign call from FATHMM, and a majority of pathogenic calls from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for P252A, and 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	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-10.587	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.97	Ambiguous	0.1	1.74	Ambiguous	1.36	Ambiguous	0.69	Ambiguous	0.831	Likely Pathogenic	-7.35	Deleterious	0.941	Possibly Damaging	0.607	Possibly Damaging	5.87	Benign	0.03	Affected			0.3490	0.4161		1	-1	3.4	-26.04
c.757A>G	N253D 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N253D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on benign effects include FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while those that predict pathogenicity are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicating likely pathogenic, whereas Foldetta predicts a benign effect on protein stability. Overall, the majority of tools (8/15) favor a pathogenic outcome, with no conflict with ClinVar status because the variant is not yet catalogued. Thus, the variant is most likely pathogenic based on current computational predictions, and this assessment does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.201744	Uncertain	0.771	0.298	0.250											-14.105	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.37	Likely Benign	0.31	Likely Benign	0.09	Likely Benign	0.742	Likely Pathogenic	-4.13	Deleterious	0.993	Probably Damaging	0.971	Probably Damaging	5.60	Benign	0.09	Tolerated			0.2248	0.5186		2	1	0.0	0.98
c.1271T>G	V424G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 V424G missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM. All other evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic consensus (3 pathogenic vs. 1 benign); and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also classifies the variant as pathogenic. No predictions are missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.050641	Structured	0.411431	Uncertain	0.973	0.248	0.000											-13.697	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	3.90	Destabilizing	0.1	4.84	Destabilizing	4.37	Destabilizing	2.44	Destabilizing	0.622	Likely Pathogenic	-6.26	Deleterious	0.994	Probably Damaging	1.000	Probably Damaging	3.34	Benign	0.00	Affected			0.1396	0.2029		-1	-3	-4.6	-42.08
c.1403T>A	M468K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M468K is listed in ClinVar (ID 642691.0) as Pathogenic and is not reported in gnomAD. All available in silico predictors classify the variant as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Thus, the variant is most likely pathogenic, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.284882	Structured	0.339253	Uncertain	0.932	0.257	0.000					Likely Pathogenic		1				-16.982	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	3.21	Destabilizing	0.1	3.30	Destabilizing	3.26	Destabilizing	2.57	Destabilizing	0.828	Likely Pathogenic	-4.61	Deleterious	0.878	Possibly Damaging	0.922	Probably Damaging	-1.34	Pathogenic	0.04	Affected	3.37	31	0.1576	0.0456		0	-1	-5.8	-3.02	188.7	69.3	0.0	0.0	-0.1	0.2			X				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 positively charged side chain of Lys468 rotates outward to escape the hydrophobic niche, forming an H-bond with the hydroxyl group of the Ser471 side chain and a salt bridge with the carboxylate group of the Glu472 side chain. This residue swap also disrupts the methionine-aromatic stacking with the phenyl ring of the Phe464 side chain. Although no large-scale structural changes are observed during the variant simulations, the importance of hydrophobic packing suggests that the effects could be more pronounced during protein folding.
c.1562A>T	E521V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521V missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized score is pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact for E521V, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-10.297	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.49	Likely Benign	0.40	Likely Benign	0.21	Likely Benign	0.413	Likely Benign	-5.15	Deleterious	0.995	Probably Damaging	0.996	Probably Damaging	3.26	Benign	0.05	Affected			0.0913	0.7104		-2	-2	7.7	-29.98
c.1579G>T	D527Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D527Y is listed in ClinVar with an uncertain significance (ClinVar ID 1698369.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: the single benign prediction from premPS versus a consensus of pathogenic predictions from the remaining 12 tools (REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Protein‑stability calculations from FoldX and Rosetta are also uncertain. Overall, the preponderance of evidence indicates that D527Y is most likely pathogenic, which does not contradict the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.021908	Uncertain	0.913	0.408	0.000					Uncertain		1				-15.386	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	-0.77	Ambiguous	0.2	1.89	Ambiguous	0.56	Ambiguous	-0.14	Likely Benign	0.905	Likely Pathogenic	-8.79	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-2.41	Pathogenic	0.00	Affected	3.37	35	0.0554	0.4229		-4	-3	2.2	48.09	270.9	-45.7	0.1	0.1	-0.1	0.0		X						Potentially Pathogenic	Asp527 is located on an α-α loop between the two α-helices (res. Gly502-Tyr518 and Ala533-Val560). In the WT simulations, the carboxylate group of the Asp527 side chain forms hydrogen bonds with the backbone atoms of loop residues (e.g., Ile529, Lys530) facing the membrane surface. In the variant simulations, Tyr527 is a bulkier residue that faces away from the loop and stacks with Phe646 in a nearby α-helix (res. Ser614-Ser668). Regardless, no negative structural effects are observed during the variant simulations. However, due to its location near the SynGAP-membrane interface, the effect of the residue swap cannot be fully addressed using the SynGAP solvent-only simulations.
c.1670C>A	S557Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S557Y is not reported in ClinVar and has no gnomAD entry. Prediction tools largely agree on a deleterious effect: all except premPS (which predicts benign) return pathogenic or likely pathogenic. The high‑accuracy methods reinforce this: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No tool indicates a benign outcome. Consequently, the variant is most likely pathogenic according to the available computational evidence, and this assessment does not conflict with ClinVar status, which currently contains no entry for S557Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.010261	Uncertain	0.924	0.215	0.000											-13.792	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	18.89	Destabilizing	1.1	3.48	Destabilizing	11.19	Destabilizing	-0.20	Likely Benign	0.965	Likely Pathogenic	-5.45	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.77	Pathogenic	0.00	Affected			0.1157	0.6087		-3	-2	-0.5	76.10
c.1820T>G	L607R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L607R is 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 algorithms—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. Rosetta and Foldetta provide uncertain results and are therefore treated as unavailable evidence. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” while Foldetta remains uncertain. 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 annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-14.234	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	-0.15	Likely Benign	0.1	1.48	Ambiguous	0.67	Ambiguous	1.24	Destabilizing	0.920	Likely Pathogenic	-5.98	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.51	Pathogenic	0.01	Affected			0.1490	0.0615		-3	-2	-8.3	43.03
c.1838A>T	E613V 2D 3DClick to see structure in 3D Viewer AISynGAP1 E613V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are Foldetta and premPS, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. FoldX and Rosetta give uncertain results and are not included in the agreement groups. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Because the majority of evidence points to a deleterious effect, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.193489	Uncertain	0.816	0.254	0.000											-12.799	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.5	-0.76	Ambiguous	-0.02	Likely Benign	0.31	Likely Benign	0.767	Likely Pathogenic	-6.57	Deleterious	0.996	Probably Damaging	0.991	Probably Damaging	-1.25	Pathogenic	0.03	Affected			0.0935	0.6565		-2	-2	7.7	-29.98
c.1893G>C	Q631H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q631H is reported in gnomAD (6‑33440945‑G‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (Rosetta, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) all indicate a pathogenic impact. Uncertain results come from FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.038963	Uncertain	0.948	0.230	0.000								6-33440945-G-C	2	1.24e-6	-13.282	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.84	Ambiguous	0.2	2.21	Destabilizing	1.53	Ambiguous	0.84	Ambiguous	0.475	Likely Benign	-4.98	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	2.75	Benign	0.00	Affected	3.37	34	0.0834	0.1757		0	3	0.3	9.01
c.1893G>T	Q631H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q631H is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, whereas the majority of algorithms—including AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, Rosetta, and the SGM Consensus—classify the change as pathogenic. Predictions from FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while Foldetta’s stability analysis is uncertain. Overall, the preponderance of evidence points to a pathogenic impact for Q631H, which is consistent with the absence of a benign ClinVar annotation and the lack of population data in gnomAD. 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											-13.282	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.84	Ambiguous	0.2	2.21	Destabilizing	1.53	Ambiguous	0.84	Ambiguous	0.475	Likely Benign	-4.98	Deleterious	0.995	Probably Damaging	0.986	Probably Damaging	2.75	Benign	0.00	Affected	3.37	34	0.0834	0.1757		0	3	0.3	9.01
c.1915T>A	F639I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F639I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FATHMM and Rosetta, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.117665	Uncertain	0.942	0.284	0.000											-12.548	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	4.32	Destabilizing	0.3	0.47	Likely Benign	2.40	Destabilizing	1.44	Destabilizing	0.545	Likely Pathogenic	-5.98	Deleterious	0.994	Probably Damaging	0.659	Possibly Damaging	3.08	Benign	0.01	Affected			0.2070	0.1755		1	0	1.7	-34.02
c.1949A>C	N650T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N650T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, and FATHMM, whereas a larger group predicts pathogenicity: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results come from Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as inconclusive. Overall, the majority of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.086953	Structured	0.361944	Uncertain	0.961	0.357	0.000											-13.626	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.31	Likely Benign	0.1	0.73	Ambiguous	0.52	Ambiguous	0.69	Ambiguous	0.471	Likely Benign	-5.98	Deleterious	0.986	Probably Damaging	0.710	Possibly Damaging	3.04	Benign	0.01	Affected			0.1700	0.4843		0	0	2.8	-13.00
c.1967A>G	E656G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E656G missense variant has no ClinVar entry and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Only premPS and FATHMM predict a benign outcome, while FoldX and Foldetta are inconclusive. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for E656G, and this conclusion is not contradicted by ClinVar status, which currently lacks an entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.032017	Structured	0.242242	Uncertain	0.963	0.264	0.000											-14.112	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.1	2.02	Destabilizing	1.49	Ambiguous	0.22	Likely Benign	0.534	Likely Pathogenic	-6.28	Deleterious	1.000	Probably Damaging	0.941	Probably Damaging	3.44	Benign	0.05	Affected			0.3216	0.5208		0	-2	3.1	-72.06
c.2065C>T	L689F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Two tools (Rosetta and premPS) yield uncertain results. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No prediction or stability result is missing or inconclusive. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-9.817	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	2.45	Destabilizing	0.2	1.95	Ambiguous	2.20	Destabilizing	0.67	Ambiguous	0.286	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.860	Possibly Damaging	3.18	Benign	0.00	Affected			0.0608	0.2891		2	0	-1.0	34.02
c.2077C>A	H693N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and FATHMM, whereas the majority of other in silico predictors—premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—label it pathogenic. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy methods specifically give AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for H693N, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000											-12.275	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.1	0.80	Ambiguous	1.27	Ambiguous	1.28	Destabilizing	0.436	Likely Benign	-6.98	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.10	Benign	0.01	Affected			0.1380	0.1849		2	1	-0.3	-23.04
c.2111G>T	S704I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704I lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) report a pathogenic or likely pathogenic outcome. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy methods specifically give AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-14.222	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.1	1.32	Ambiguous	1.48	Ambiguous	0.29	Likely Benign	0.232	Likely Benign	-4.05	Deleterious	0.997	Probably Damaging	0.758	Possibly Damaging	3.49	Benign	0.02	Affected			0.0727	0.4798		-1	-2	5.3	26.08
c.253A>C	T85P 2D AIThe SynGAP1 missense variant T85P is not 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 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear majority and is therefore unavailable; Foldetta results are not provided. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate a pathogenic effect. There is no ClinVar entry to contradict this assessment, so 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.			0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-8.406	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.28	Neutral	0.813	Possibly Damaging	0.053	Benign	3.80	Benign	0.00	Affected			0.1499	0.4485		0	-1	-0.9	-3.99
c.253A>G	T85A 2D AIThe SynGAP1 missense variant T85A is not reported in ClinVar and is absent from gnomAD. Consensus and most in‑silico predictors classify it as benign: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM all indicate a benign effect. In contrast, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict a pathogenic impact. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized reports a pathogenic change, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools and the consensus prediction lean toward a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.680603	Disordered	0.542004	Binding	0.288	0.888	0.500											-4.803	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.101	Likely Benign	-1.79	Neutral	0.060	Benign	0.004	Benign	3.88	Benign	0.00	Affected			0.3155	0.3517		1	0	2.5	-30.03
c.3455A>T	E1152V 2D AIThe SynGAP1 missense variant E1152V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500											-3.304	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.408	Likely Benign	-4.65	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1247	0.6384		-2	-2	7.7	-29.98
c.3478A>G	N1160D 2D AIThe SynGAP1 missense variant at position N1160D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas a majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.222	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.225	Likely Benign	-3.22	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.84	Pathogenic	0.08	Tolerated			0.1618	0.3920		2	1	0.0	0.98
c.3478A>T	N1160Y 2D AIThe SynGAP1 missense variant N1160Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability prediction is available. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-4.074	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.421	Likely Benign	-4.90	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.79	Pathogenic	0.01	Affected			0.0591	0.5681		-2	-2	2.2	49.07
c.3497C>A	A1166D 2D AIThe SynGAP1 missense variant A1166D is not 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. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence (five benign vs. four pathogenic) and the consensus score lean toward a benign interpretation, with no conflict with ClinVar status. Thus, the variant is most likely benign, although the AlphaMissense‑Optimized prediction introduces some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.811691	Binding	0.381	0.803	0.375											-4.204	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.417	Likely Benign	-1.56	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	5.29	Benign	0.42	Tolerated			0.1709	0.2104		0	-2	-5.3	44.01
c.3580A>G	R1194G 2D AIThe SynGAP1 missense variant R1194G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of conventional tools lean toward pathogenicity, and the high‑accuracy predictions are split, with no ClinVar evidence to contradict the pathogenic interpretation. Thus, the variant is most likely pathogenic based on the current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-6.849	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic										0.477	Likely Benign	-2.17	Neutral	0.991	Probably Damaging	0.991	Probably Damaging	5.56	Benign	0.02	Affected			0.3275	0.2847		-3	-2	4.1	-99.14
c.3580A>T	R1194W 2D AIThe SynGAP1 missense variant R1194W is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to the variant being most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375											-9.583	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.514	Likely Pathogenic	-2.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.41	Benign	0.00	Affected			0.1252	0.3162		2	-3	3.6	30.03
c.3623G>T	R1208L 2D AIThe SynGAP1 missense variant R1208L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that R1208L is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-10.576	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.70	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.51	Benign	0.01	Affected			0.1621	0.3816		-3	-2	8.3	-43.03
c.3655T>A	Y1219N 2D AIThe SynGAP1 missense variant Y1219N is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact largely agree on a deleterious effect: SIFT, polyPhen‑2 (HumDiv and HumVar), PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the only benign prediction comes from REVEL. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as “Likely Pathogenic.” High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-11.679	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.366	Likely Benign	-6.41	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.2478	0.0573		-2	-2	-2.2	-49.07
c.3679G>A	E1227K 2D AIThe SynGAP1 missense variant E1227K is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500											-11.825	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.280	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.1661	0.6348		0	1	-0.4	-0.94
c.3796C>G	L1266V 2D AIThe SynGAP1 missense variant L1266V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-10.024	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.53	Deleterious	0.995	Probably Damaging	0.890	Possibly Damaging	2.16	Pathogenic	0.00	Affected			0.1301	0.3118		2	1	0.4	-14.03
c.3810G>C	E1270D 2D AIThe SynGAP1 missense variant E1270D is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250											-9.379	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1655	0.3271		3	2	0.0	-14.03
c.3810G>T	E1270D 2D AIThe SynGAP1 missense variant E1270D is catalogued in gnomAD (6-33447858‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic.” The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence indicates that E1270D is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.771865	Binding	0.805	0.659	0.250								6-33447858-G-T			-9.379	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1655	0.3271		3	2	0.0	-14.03
c.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	-3.54	Deleterious	0.247	Benign	0.166	Benign	3.63	Benign	0.00	Affected			0.1965	0.3611		0	-1	3.2	-27.07
c.508C>T	R170W 2D AIThe SynGAP1 missense variant R170W is listed in ClinVar (ID 1310195.0) 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 (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus indicates it is likely pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250					Uncertain		2				-11.660	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.241	Likely Benign	-4.28	Deleterious	0.999	Probably Damaging	0.849	Possibly Damaging	3.84	Benign	0.00	Affected	3.74	4	0.1026	0.3469		2	-3	3.6	30.03
c.521T>A	M174K 2D AIThe SynGAP1 missense variant M174K has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic, and AlphaMissense‑Optimized independently predicts it as Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence from high‑accuracy predictors and the consensus score points to a pathogenic classification. This assessment is not contradicted by ClinVar, which currently contains no entry for M174K. 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											-9.542	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.325	Likely Benign	-3.21	Deleterious	0.002	Benign	0.002	Benign	4.06	Benign	0.01	Affected			0.1373	0.0688		0	-1	-5.8	-3.02
c.547C>A	H183N 2D AIThe SynGAP1 H183N missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic impact are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of predictions, including the high‑accuracy tools, point to a pathogenic effect, 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		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-12.028	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-4.97	Deleterious	0.012	Benign	0.006	Benign	3.81	Benign	0.01	Affected			0.1714	0.2589		2	1	-0.3	-23.04
c.547C>T	H183Y 2D AIThe SynGAP1 H183Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, 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. Overall, the majority of computational evidence points to a pathogenic impact, 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		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-9.481	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.250	Likely Benign	-4.48	Deleterious	0.818	Possibly Damaging	0.255	Benign	3.77	Benign	0.00	Affected			0.0831	0.4406		0	2	1.9	26.03
c.583G>C	A195P 2D AIThe SynGAP1 missense variant A195P is listed in ClinVar as Pathogenic (ClinVar ID 375527.0) and is not reported in gnomAD. Prediction tools that indicate a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence supports a pathogenic classification, which aligns with the ClinVar status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.346032	Structured	0.430388	Uncertain	0.363	0.533	0.125					Likely Pathogenic		1				-9.715	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.152	Likely Benign	-3.03	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	4.00	Benign	0.04	Affected	3.54	6	0.1403	0.4402		1	-1	-3.4	26.04
c.652T>G	F218V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F218V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; pathogenic predictions arise from REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus agrees on a likely pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenicity. No predictions or stability results are missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion aligns with the absence of a ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.281712	Structured	0.408725	Uncertain	0.848	0.272	0.000											-10.081	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	4.18	Destabilizing	0.2	6.35	Destabilizing	5.27	Destabilizing	1.15	Destabilizing	0.691	Likely Pathogenic	-4.14	Deleterious	0.300	Benign	0.066	Benign	5.81	Benign	0.08	Tolerated			0.2173	0.2258		-1	-1	1.4	-48.04
c.833A>C	K278T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any ClinVar annotation 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	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-11.227	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.85	Ambiguous	0.2	-0.08	Likely Benign	0.39	Likely Benign	0.46	Likely Benign	0.484	Likely Benign	-5.40	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.70	Pathogenic	0.04	Affected			0.1775	0.2220		0	-1	3.2	-27.07
c.847G>C	E283Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E283Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise 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). The premPS score is uncertain and does not contribute to the consensus. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of tools (nine 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 for this variant. 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											-10.650	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.48	Likely Benign	0.1	-0.01	Likely Benign	0.24	Likely Benign	0.61	Ambiguous	0.372	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.67	Pathogenic	0.01	Affected			0.1432	0.5389		2	2	0.0	-0.98
c.1308G>C	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1308G>T	E436D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E436D missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions are limited to FATHMM, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict pathogenicity. Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also pathogenic (3 pathogenic vs. 1 benign). Foldetta’s stability prediction is uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000											-10.355	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.55	Ambiguous	0.1	0.71	Ambiguous	0.63	Ambiguous	0.73	Ambiguous	0.554	Likely Pathogenic	-2.85	Deleterious	0.986	Probably Damaging	0.921	Probably Damaging	4.61	Benign	0.01	Affected			0.1938	0.3553		3	2	0.0	-14.03
c.1393C>T	L465F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465F is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and Rosetta, whereas the majority of tools predict a pathogenic impact: 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, PROVEAN). Two tools (Foldetta and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus also pathogenic, and Foldetta remains uncertain. Overall, the consensus of high‑confidence predictors points to a pathogenic effect for L465F. 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	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-12.626	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	3.11	Destabilizing	0.7	0.05	Likely Benign	1.58	Ambiguous	0.52	Ambiguous	0.432	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.0771	0.2759		2	0	-1.0	34.02
c.1421A>C	D474A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474A missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, premPS, and SIFT, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, SGM Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000											-11.082	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.08	Likely Benign	0.0	0.15	Likely Benign	0.12	Likely Benign	0.17	Likely Benign	0.757	Likely Pathogenic	-6.73	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.22	Pathogenic	0.22	Tolerated			0.3265	0.4354		0	-2	5.3	-44.01
c.1517T>G	L506R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506R 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. Thus, all available evidence indicates that the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-14.119	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	4.92	Destabilizing	0.6	5.85	Destabilizing	5.39	Destabilizing	1.77	Destabilizing	0.738	Likely Pathogenic	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1207	0.0488		-3	-2	-8.3	43.03
c.1633A>G	M545V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545V is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include SIFT and Rosetta, while a majority of tools predict a pathogenic outcome: PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus. Tools with inconclusive results (FoldX, Foldetta, premPS, ESM1b) are considered unavailable for interpretation. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for M545V. This conclusion is not contradicted by ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000											-7.481	In-Between	0.979	Likely Pathogenic	Likely Pathogenic	0.91	Ambiguous	0.1	0.33	Likely Benign	0.62	Ambiguous	0.94	Ambiguous	0.688	Likely Pathogenic	-3.54	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.26	Pathogenic	0.34	Tolerated			0.2454	0.2953		2	1	2.3	-32.06
c.1843C>G	P615A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P615A variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include SIFT and Rosetta, whereas the majority of predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) and the SGM‑Consensus score (Likely Pathogenic) all suggest a pathogenic impact. Uncertain results are reported by FoldX, Foldetta, and premPS. 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’s stability analysis is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for P615A, 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	0.236433	Structured	0.179032	Uncertain	0.879	0.255	0.000											-12.156	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	1.73	Ambiguous	0.3	0.35	Likely Benign	1.04	Ambiguous	0.85	Ambiguous	0.693	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.25	Pathogenic	0.10	Tolerated			0.3169	0.3214		1	-1	3.4	-26.04
c.1858T>C	S620P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S620P is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly favor 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 premPS remains uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.100377	Uncertain	0.936	0.219	0.000											-12.208	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	4.89	Destabilizing	0.5	12.23	Destabilizing	8.56	Destabilizing	0.73	Ambiguous	0.834	Likely Pathogenic	-3.62	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	-1.35	Pathogenic	0.02	Affected			0.2147	0.4776		1	-1	-0.8	10.04
c.1865C>T	T622I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T622I is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign are Foldetta and premPS, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all predict it to be pathogenic; FoldX and Rosetta 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. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.071403	Uncertain	0.957	0.198	0.000											-13.276	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	-1.47	Ambiguous	0.1	0.67	Ambiguous	-0.40	Likely Benign	0.45	Likely Benign	0.905	Likely Pathogenic	-5.57	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	-1.57	Pathogenic	0.00	Affected			0.0855	0.4926		0	-1	5.2	12.05
c.1889T>A	I630N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I630N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts pathogenic. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.036106	Uncertain	0.966	0.236	0.000											-14.259	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	2.96	Destabilizing	0.0	2.55	Destabilizing	2.76	Destabilizing	2.39	Destabilizing	0.825	Likely Pathogenic	-4.86	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	-1.49	Pathogenic	0.00	Affected			0.0853	0.0270		-2	-3	-8.0	0.94
c.2516A>T	K839M 2D AIThe SynGAP1 missense variant K839M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL indicates a benign likelihood, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM consensus also reports a likely pathogenic outcome. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-13.688	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.241	Likely Benign	-3.54	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.40	Pathogenic	0.00	Affected			0.1253	0.4481		0	-1	5.8	3.02
c.265C>A	P89T 2D AIThe SynGAP1 missense variant P89T has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta stability analysis is unavailable. Overall, the preponderance of evidence leans toward a benign effect, but the presence of a pathogenic prediction from AlphaMissense‑Optimized introduces uncertainty. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-5.429	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-2.49	Neutral	0.588	Possibly Damaging	0.036	Benign	3.74	Benign	0.00	Affected			0.1786	0.4702		0	-1	0.9	3.99
c.265C>T	P89S 2D AIThe SynGAP1 missense variant P89S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (majority vote) indicates likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, and this assessment does not contradict the absence of a ClinVar classification. Thus, based on the available computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-5.198	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-2.40	Neutral	0.225	Benign	0.020	Benign	3.76	Benign	0.00	Affected			0.3459	0.4191		1	-1	0.8	-10.04
c.2789C>G	P930R 2D AIThe SynGAP1 missense variant P930R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. No tool in the dataset predicts a benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the consensus of available predictions indicates that P930R is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry (i.e., no contradictory status). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-9.474	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.505	Likely Pathogenic	-6.67	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0.1460	0.3515		0	-2	-2.9	59.07
c.3233T>A	V1078D 2D AIThe SynGAP1 missense variant V1078D is listed in ClinVar (ID 2993122.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default, AlphaMissense‑Optimized, 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 pathogenic, SGM‑Consensus as likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the ClinVar “Uncertain” designation; there is no contradiction with the existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.986989	Binding	0.294	0.898	0.750					Uncertain		1				-5.155	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.158	Likely Benign	-1.45	Neutral	0.003	Benign	0.008	Benign	3.84	Benign	0.00	Affected	3.77	5	0.1570	0.1173		-3	-2	-7.7	15.96
c.3494C>G	S1165W 2D AIThe SynGAP1 missense variant S1165W has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); 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 a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the evidence is split, with an equal number of tools supporting benign versus pathogenic effects. Consequently, the variant is most likely pathogenic based on the current computational predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.835017	Binding	0.308	0.807	0.375											-6.419	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-2.29	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.54	Benign	0.02	Affected			0.0671	0.4807		-2	-3	-0.1	99.14
c.3557C>G	S1186W 2D AIThe SynGAP1 missense variant S1186W is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—also favors pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that S1186W is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.506433	Binding	0.634	0.636	0.625											-7.814	In-Between	0.979	Likely Pathogenic	Likely Pathogenic										0.214	Likely Benign	-3.43	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.62	Benign	0.01	Affected			0.0556	0.4158		-2	-3	-0.1	99.14
c.3688A>C	T1230P 2D AIThe SynGAP1 missense variant T1230P is not reported in ClinVar and has no entries in gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta results are unavailable, so no additional stability evidence is provided. Overall, the consensus of available predictions points to a pathogenic effect for T1230P, with no conflict from ClinVar status (which is currently unreported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.570702	Disordered	0.486342	Uncertain	0.845	0.543	0.250											-13.200	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.588	Likely Pathogenic	-2.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	5.54	Benign	0.01	Affected			0.1529	0.3710		0	-1	-0.9	-3.99
c.394T>G	F132V 2D AIThe SynGAP1 missense variant F132V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictions indicate a pathogenic effect, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-7.637	In-Between	0.979	Likely Pathogenic	Likely Pathogenic										0.328	Likely Benign	-3.86	Deleterious	0.084	Benign	0.034	Benign	3.38	Benign	0.00	Affected			0.2349	0.1725		-1	-1	1.4	-48.04
c.424A>C	K142Q 2D AIThe SynGAP1 missense variant K142Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of computational evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-11.295	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-2.50	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.50	Benign	0.00	Affected			0.4232	0.1132		1	1	0.4	-0.04
c.732G>C	E244D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX and FATHMM, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported by Rosetta, Foldetta, premPS, and ESM1b. 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 remains uncertain. Overall, the balance of evidence favors a pathogenic classification for E244D, 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.		PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-7.839	In-Between	0.979	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.1	1.61	Ambiguous	1.04	Ambiguous	0.93	Ambiguous	0.730	Likely Pathogenic	-2.53	Deleterious	0.976	Probably Damaging	0.675	Possibly Damaging	5.78	Benign	0.03	Affected			0.1740	0.3783		3	2	0.0	-14.03
c.732G>T	E244D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E244D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX and FATHMM, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results come from Rosetta, Foldetta, premPS, and ESM1b. 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 remains uncertain. Overall, the balance of evidence points to a likely pathogenic effect for E244D, 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.		PH	0.450668	Structured	0.329406	Uncertain	0.778	0.360	0.000											-7.839	In-Between	0.979	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.1	1.61	Ambiguous	1.04	Ambiguous	0.93	Ambiguous	0.730	Likely Pathogenic	-2.53	Deleterious	0.976	Probably Damaging	0.675	Possibly Damaging	5.78	Benign	0.03	Affected			0.1740	0.3783		3	2	0.0	-14.03
c.743G>A	R248Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R248Q is catalogued in gnomAD (ID 6‑33435594‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: benign predictions come from FoldX and FATHMM, whereas pathogenic predictions are made by REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are reported by Rosetta and Foldetta. 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 remains Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for R248Q, and this conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.267126	Uncertain	0.781	0.346	0.250								6-33435594-G-A	2	1.24e-6	-10.573	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.45	Likely Benign	0.2	1.67	Ambiguous	1.06	Ambiguous	1.05	Destabilizing	0.739	Likely Pathogenic	-3.34	Deleterious	0.999	Probably Damaging	0.715	Possibly Damaging	5.74	Benign	0.01	Affected	3.41	14	0.2572	0.2549		1	1	1.0	-28.06
c.760A>C	K254Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K254Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, SIFT, and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools, Rosetta and premPS, give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375											-12.332	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.13	Likely Benign	0.1	-0.61	Ambiguous	-0.24	Likely Benign	0.90	Ambiguous	0.737	Likely Pathogenic	-3.04	Deleterious	0.997	Probably Damaging	0.879	Possibly Damaging	5.91	Benign	0.11	Tolerated			0.3749	0.1483		1	1	0.4	-0.04
c.862G>T	D288Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288Y missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, and premPS; pathogenic predictions from SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from the available tools suggests a benign effect. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-15.269	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.11	Likely Benign	0.2	1.10	Ambiguous	0.61	Ambiguous	0.10	Likely Benign	0.472	Likely Benign	-7.11	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			0.0635	0.5009		-4	-3	2.2	48.09
c.1216T>A	Y406N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y406N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also indicates pathogenicity. Taken together, the preponderance of evidence points to a pathogenic effect for Y406N, 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	C2	0.179055	Structured	0.393707	Uncertain	0.946	0.291	0.000											-13.206	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	2.90	Destabilizing	0.1	2.88	Destabilizing	2.89	Destabilizing	1.58	Destabilizing	0.288	Likely Benign	-7.11	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	3.78	Benign	0.02	Affected			0.2532	0.1071		-2	-2	-2.2	-49.07
c.1256A>T	E419V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E419V missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, FoldX, FATHMM, and premPS, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from the high‑accuracy tools contradicts the pathogenic prediction. Overall, the majority of computational evidence points to a pathogenic effect, which is consistent with the lack of ClinVar reporting and gnomAD absence, suggesting the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.371949	Uncertain	0.961	0.261	0.000											-12.290	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.45	Likely Benign	0.0	1.41	Ambiguous	0.93	Ambiguous	0.27	Likely Benign	0.494	Likely Benign	-6.55	Deleterious	0.998	Probably Damaging	0.983	Probably Damaging	3.35	Benign	0.01	Affected			0.0953	0.6834		-2	-2	7.7	-29.98
c.1357C>G	H453D 2D 3DClick to see structure in 3D Viewer AISynGAP1 H453D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are made by FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods reinforce a pathogenic interpretation: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenicity. premPS remains uncertain. Overall, the majority of evidence points to a pathogenic effect for H453D, and this conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000											-15.256	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	3.33	Destabilizing	0.0	2.68	Destabilizing	3.01	Destabilizing	0.97	Ambiguous	0.443	Likely Benign	-8.89	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.48	Benign	0.09	Tolerated			0.2225	0.1815		1	-1	-0.3	-22.05
c.1373C>G	T458R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T458R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, and FATHMM, whereas a larger set—SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict pathogenicity. Uncertain results come from FoldX and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.185198	Structured	0.294848	Uncertain	0.915	0.144	0.000											-12.984	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	-0.81	Ambiguous	0.1	-0.11	Likely Benign	-0.46	Likely Benign	0.61	Ambiguous	0.390	Likely Benign	-5.26	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.52	Benign	0.20	Tolerated			0.1016	0.3013		-1	-1	-3.8	55.08
c.1375G>T	G459C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G459C 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, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Uncertain or inconclusive results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence points to a pathogenic effect for G459C, 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	0.289888	Uncertain	0.903	0.150	0.125											-12.109	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	2.46	Destabilizing	0.2	1.49	Ambiguous	1.98	Ambiguous	0.65	Ambiguous	0.586	Likely Pathogenic	-8.46	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.00	Benign	0.00	Affected			0.0960	0.4103		-3	-3	2.9	46.09
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	3.65	Destabilizing	0.2	9.24	Destabilizing	6.45	Destabilizing	0.84	Ambiguous	0.530	Likely Pathogenic	-4.03	Deleterious	0.552	Possibly Damaging	0.141	Benign	-1.31	Pathogenic	0.05	Affected			0.2007	0.4769		1	-1	-0.8	10.04
c.1457A>C	E486A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E486A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, premPS, SIFT, and FATHMM, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore unavailable. Overall, the majority of evidence supports a pathogenic effect. The prediction aligns with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.196879	Structured	0.358545	Uncertain	0.833	0.245	0.125											-11.902	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.32	Likely Benign	0.48	Likely Benign	-0.03	Likely Benign	0.398	Likely Benign	-5.17	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	3.44	Benign	0.39	Tolerated			0.3561	0.5859		0	-1	5.3	-58.04