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.2618G>A	S873N 2D AIThe SynGAP1 missense variant S873N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S873N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-6.453	Likely Benign	0.706	Likely Pathogenic	Likely Benign										0.180	Likely Benign	-1.88	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.66	Benign	0.12	Tolerated			0.1440	0.4612		1	1	-2.7	27.03
c.2681G>A	G894E 2D AIThe SynGAP1 missense variant G894E is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443233‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is reported as uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and no Foldetta (FoldX‑MD/Rosetta) result is available. Overall, the majority of predictions support a benign impact, and this is consistent with the ClinVar “Uncertain” classification; thus the variant is most likely benign and does not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.425700	Uncertain	0.310	0.925	0.750					Uncertain		1	6-33443233-G-A	6	3.72e-6	-5.377	Likely Benign	0.859	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-2.07	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.68	Benign	0.01	Affected	4.32	4	0.1489	0.3686		0	-2	-3.1	72.06
c.2681G>C	G894A 2D AIThe SynGAP1 missense variant G894A is reported in gnomAD (ID 6‑33443233‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.425700	Uncertain	0.310	0.925	0.750								6-33443233-G-C	1	6.20e-7	-3.997	Likely Benign	0.267	Likely Benign	Likely Benign										0.180	Likely Benign	-1.26	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	2.69	Benign	0.97	Tolerated	4.32	4	0.3857	0.4670		0	1	2.2	14.03
c.2795T>A	F932Y 2D AIThe SynGAP1 missense variant F932Y is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of other predictors (polyPhen‑2 HumDiv and HumVar) suggest pathogenic. When predictions are grouped by agreement, the benign‑predicating tools outnumber the pathogenic ones, and the single uncertain call from AlphaMissense‑Default does not alter this balance. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as Likely Benign. Foldetta data are unavailable. Overall, the computational evidence overwhelmingly supports a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.989197	Binding	0.293	0.858	0.500											-5.248	Likely Benign	0.540	Ambiguous	Likely Benign										0.180	Likely Benign	1.58	Neutral	0.997	Probably Damaging	0.987	Probably Damaging	3.13	Benign	0.74	Tolerated			0.1473	0.2003		7	3	-4.1	16.00
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.3272T>C	L1091P 2D AIThe SynGAP1 missense variant L1091P is listed in gnomAD (ID 6‑33443824‑T‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and ESM1b, while pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, leaving it inconclusive. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools (five pathogenic vs three benign) predict a deleterious effect, and the high‑accuracy AlphaMissense‑Optimized score is uncertain. Consequently, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000								6-33443824-T-C			-4.139	Likely Benign	0.871	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-1.25	Neutral	0.997	Probably Damaging	0.939	Probably Damaging	2.45	Pathogenic	0.04	Affected	3.77	5	0.3199	0.1918		-3	-3	-5.4	-16.04
c.3397A>G	I1133V 2D AIThe SynGAP1 missense variant I1133V is listed in ClinVar as Benign (ClinVar ID 999690.0) and is present in the gnomAD database (gnomAD ID 6‑33443949‑A‑G). All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. Foldetta results are unavailable. Consequently, the variant is most likely benign, and this prediction aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.832785	Binding	0.316	0.892	0.750					Benign		1	6-33443949-A-G	22	1.48e-5	-3.362	Likely Benign	0.067	Likely Benign	Likely Benign										0.180	Likely Benign	0.06	Neutral	0.007	Benign	0.007	Benign	5.47	Benign	0.58	Tolerated	4.32	3	0.1190	0.3985		4	3	-0.3	-14.03																10.1016/j.ajhg.2020.11.011
c.3499G>A	D1167N 2D AIThe SynGAP1 missense variant D1167N is not 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 predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 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 interpretation. This prediction does not contradict any ClinVar status, as the variant is not yet catalogued in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500											-3.671	Likely Benign	0.924	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-1.72	Neutral	0.995	Probably Damaging	0.963	Probably Damaging	2.33	Pathogenic	0.01	Affected			0.1315	0.7940		2	1	0.0	-0.98
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.3991A>C	I1331L 2D AIThe SynGAP1 missense variant I1331L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify 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 Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, with no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.941705	Binding	0.359	0.752	0.875											-2.450	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.180	Likely Benign	-1.04	Neutral	0.762	Possibly Damaging	0.785	Possibly Damaging	3.45	Benign	0.00	Affected			0.0752	0.3616		2	2	-0.7	0.00
c.466T>C	F156L 2D AIThe SynGAP1 missense variant F156L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of conventional tools predict pathogenicity, but the high‑accuracy consensus is ambiguous. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500											-7.437	In-Between	0.996	Likely Pathogenic	Likely Pathogenic										0.180	Likely Benign	-2.31	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.04	Benign	0.00	Affected			0.2067	0.3109		2	0	1.0	-34.02
c.577G>T	A193S 2D AIThe SynGAP1 missense variant A193S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-2.408	Likely Benign	0.533	Ambiguous	Likely Benign										0.180	Likely Benign	-1.62	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	4.04	Benign	0.04	Affected			0.2595	0.5852		1	1	-2.6	16.00
c.157G>A	G53R 2D AIThe SynGAP1 missense variant G53R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic + 2 benign), and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic impact. Because there is no ClinVar entry to contradict this assessment, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.400	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.20	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.13	Benign	0.00	Affected			0.0953	0.4347		-3	-2	-4.1	99.14
c.157G>C	G53R 2D AIThe SynGAP1 missense variant G53R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic + 2 benign), and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable. Overall, the majority of tools (5 pathogenic vs. 3 benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-8.400	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.20	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	4.13	Benign	0.00	Affected			0.0953	0.4347		-3	-2	-4.1	99.14
c.2326G>C	G776R 2D AIThe SynGAP1 missense variant G776R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the Foldetta protein‑folding stability assessment is unavailable for this variant. 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		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250											-6.209	Likely Benign	0.886	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.28	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	4.22	Benign	0.01	Affected			0.0932	0.5115		-3	-2	-4.1	99.14
c.2326G>T	G776C 2D AIThe SynGAP1 missense variant G776C is not reported in ClinVar but is present in gnomAD (ID 6‑33442484‑G‑T). Prediction tools cluster into benign (REVEL, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). Two tools (ESM1b, AlphaMissense‑Default) return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, whereas the single high‑accuracy tool suggests benign. Given the preponderance of pathogenic predictions and the absence of a ClinVar entry, the variant is most likely pathogenic and does not contradict any existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442484-G-T			-7.974	In-Between	0.380	Ambiguous	Likely Benign										0.181	Likely Benign	-2.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	4.15	Benign	0.01	Affected	3.64	6	0.1235	0.4403		-3	-3	2.9	46.09
c.2498A>T	K833M 2D AIThe SynGAP1 missense variant K833M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evaluated predictors (six benign vs. four pathogenic) support a benign classification. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-3.234	Likely Benign	0.685	Likely Pathogenic	Likely Benign										0.181	Likely Benign	-2.05	Neutral	0.997	Probably Damaging	0.954	Probably Damaging	2.55	Benign	0.01	Affected			0.0867	0.3652		0	-1	5.8	3.02
c.2515A>G	K839E 2D AIThe SynGAP1 missense variant K839E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic predictions versus four benign, plus a Likely Pathogenic consensus—suggests the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-12.616	Likely Pathogenic	0.931	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.90	Neutral	0.316	Benign	0.139	Benign	2.47	Pathogenic	0.01	Affected			0.3822	0.1198		0	1	0.4	0.94
c.2527A>C	M843L 2D AIThe SynGAP1 missense variant M843L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of benign predictions and the lack of pathogenic evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-4.406	Likely Benign	0.426	Ambiguous	Likely Benign										0.181	Likely Benign	-1.02	Neutral	0.699	Possibly Damaging	0.833	Possibly Damaging	2.92	Benign	0.33	Tolerated			0.1717	0.4571		4	2	1.9	-18.03
c.2527A>T	M843L 2D AIThe SynGAP1 missense variant M843L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-4.406	Likely Benign	0.426	Ambiguous	Likely Benign										0.181	Likely Benign	-1.02	Neutral	0.699	Possibly Damaging	0.833	Possibly Damaging	2.92	Benign	0.33	Tolerated			0.1717	0.4571		4	2	1.9	-18.03
c.2693C>T	S898F 2D AIThe SynGAP1 missense variant S898F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500											-5.242	Likely Benign	0.673	Likely Pathogenic	Likely Benign										0.181	Likely Benign	-2.87	Deleterious	0.998	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1183	0.6643		-3	-2	3.6	60.10
c.2759A>T	Q920L 2D AIThe SynGAP1 missense variant Q920L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.927260	Binding	0.306	0.845	0.250											-4.048	Likely Benign	0.280	Likely Benign	Likely Benign										0.181	Likely Benign	-2.36	Neutral	0.891	Possibly Damaging	0.596	Possibly Damaging	2.60	Benign	0.00	Affected			0.0774	0.5995		-2	-2	7.3	-14.97
c.2873A>T	H958L 2D AIThe SynGAP1 missense variant H958L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, SIFT and ESM1b, predict a pathogenic outcome. When the high‑accuracy consensus is considered, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a likely benign verdict, and AlphaMissense‑Optimized also reports benign. Foldetta predictions are unavailable. Overall, the majority of evidence supports a benign interpretation, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign and does not contradict existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.976011	Binding	0.371	0.913	0.750											-8.422	Likely Pathogenic	0.087	Likely Benign	Likely Benign										0.181	Likely Benign	-1.28	Neutral	0.001	Benign	0.001	Benign	4.25	Benign	0.03	Affected			0.1723	0.5338		-2	-3	7.0	-23.98
c.3004C>T	H1002Y 2D AIThe SynGAP1 missense variant H1002Y is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy methods that are available—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign interpretation. Therefore, the variant is most likely benign based on the current predictive evidence, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500											-6.159	Likely Benign	0.489	Ambiguous	Likely Benign										0.181	Likely Benign	-1.85	Neutral	0.961	Probably Damaging	0.808	Possibly Damaging	2.74	Benign	0.14	Tolerated			0.1243	0.4427		0	2	1.9	26.03
c.3264C>A	S1088R 2D AIThe SynGAP1 missense variant S1088R is not reported in ClinVar and is present in gnomAD (ID 6‑33443816‑C‑A). Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence—five pathogenic versus four benign predictions—suggests the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for S1088R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000								6-33443816-C-A			-4.588	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.72	Benign	0.01	Affected	3.77	5	0.1190	0.4502		-1	0	-3.7	69.11
c.3264C>G	S1088R 2D AIThe SynGAP1 missense variant S1088R has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, whereas the SGM‑Consensus remains Benign; Foldetta results are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation, with no conflict with ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-4.588	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.72	Benign	0.01	Affected	3.77	5	0.1190	0.4502		-1	0	-3.7	69.11
c.3452C>G	S1151C 2D AIThe SynGAP1 missense variant S1151C is reported in gnomAD (ID 6‑33444487‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools (polyPhen‑2 HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.741537	Disordered	0.805072	Binding	0.394	0.839	0.625								6-33444487-C-G	1	6.20e-7	-6.778	Likely Benign	0.225	Likely Benign	Likely Benign										0.181	Likely Benign	-0.86	Neutral	0.999	Probably Damaging	0.944	Probably Damaging	2.67	Benign	0.07	Tolerated	3.77	5	0.1056	0.5260		-1	0	3.3	16.06
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.3536A>T	K1179M 2D AIThe SynGAP1 missense variant K1179M is not reported in ClinVar and is absent from gnomAD. Functional 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, and Foldetta results are unavailable. Taken together, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign based on current 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											-4.429	Likely Benign	0.929	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-1.98	Neutral	0.998	Probably Damaging	0.969	Probably Damaging	2.61	Benign	0.00	Affected			0.1057	0.2715		0	-1	5.8	3.02
c.3575T>C	L1192P 2D AIThe SynGAP1 missense variant L1192P is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, 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 Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-4.610	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.959	Probably Damaging	2.65	Benign	0.05	Affected			0.3515	0.1053		-3	-3	-5.4	-16.04
c.3607C>A	H1203N 2D AIThe SynGAP1 missense variant H1203N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this view: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely benign, and Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.618285	Disordered	0.527023	Binding	0.892	0.589	0.250											-4.278	Likely Benign	0.109	Likely Benign	Likely Benign										0.181	Likely Benign	-1.07	Neutral	0.002	Benign	0.018	Benign	5.61	Benign	0.31	Tolerated			0.1155	0.0914		2	1	-0.3	-23.04
c.3742C>G	L1248V 2D AIThe SynGAP1 missense variant L1248V is not 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. AlphaMissense‑Optimized is uncertain. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (five pathogenic vs three benign) predict a deleterious impact, and no high‑accuracy consensus or folding‑stability evidence contradicts this. Therefore, the variant is most likely pathogenic, and this assessment does not conflict with the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625											-6.460	Likely Benign	0.899	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.33	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.73	Pathogenic	0.00	Affected			0.1510	0.1883		2	1	0.4	-14.03
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.4017C>G	N1339K 2D AISynGAP1 missense variant N1339K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority 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 (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑to‑2 tie, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.771762	Disordered	0.977585	Binding	0.396	0.687	1.000											-3.009	Likely Benign	0.872	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-3.56	Deleterious	0.980	Probably Damaging	0.968	Probably Damaging	2.90	Benign	0.00	Affected	3.77	5	0.2201	0.6507		0	1	-0.4	14.07
c.428G>A	R143Q 2D AIThe SynGAP1 missense variant R143Q is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33432725‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, 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, PROVEAN) is inconclusive (2 pathogenic vs 2 benign), and Foldetta stability analysis is unavailable. Overall, the majority of predictions (5 pathogenic vs 4 benign) and the pathogenic call from AlphaMissense‑Optimized suggest 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.			0.575842	Disordered	0.538584	Binding	0.338	0.838	0.625								6-33432725-G-A	2	1.35e-6	-12.110	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-2.48	Neutral	0.678	Possibly Damaging	0.176	Benign	3.53	Benign	0.00	Affected	3.61	5	0.3255	0.2678		1	1	1.0	-28.06
c.455G>A	R152Q 2D AIThe SynGAP1 missense variant R152Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33432752‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus remains unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no reported result for this variant. Overall, the preponderance of evidence (seven pathogenic versus three benign predictions) 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.			0.618285	Disordered	0.500158	Binding	0.319	0.842	0.625					Uncertain		1	6-33432752-G-A	5	3.14e-6	-10.336	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.181	Likely Benign	-2.34	Neutral	0.997	Probably Damaging	0.968	Probably Damaging	3.89	Benign	0.00	Affected	3.61	5	0.3618	0.2996		1	1	1.0	-28.06
c.505G>C	D169H 2D AIThe SynGAP1 D169H 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 effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the majority of computational evidence points toward 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		0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125											-12.048	Likely Pathogenic	0.921	Likely Pathogenic	Ambiguous										0.181	Likely Benign	-2.83	Deleterious	0.651	Possibly Damaging	0.417	Benign	4.03	Benign	0.00	Affected			0.1791	0.7624		1	-1	0.3	22.05
c.118G>T	D40Y 2D AIThe SynGAP1 D40Y missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for D40Y, 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 Benign		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-4.313	Likely Benign	0.483	Ambiguous	Likely Benign										0.182	Likely Benign	-1.72	Neutral	0.388	Benign	0.328	Benign	3.98	Benign	0.00	Affected			0.1173	0.7918		-4	-3	2.2	48.09
c.1557A>T	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E519D is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM, while those that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicating a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign interpretation. This consensus does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.182	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.1876A>G	I626V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I626V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are uncertain or unavailable are AlphaMissense‑Default, FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also indicates a likely benign outcome, while Foldetta’s stability analysis is inconclusive. Based on the overall consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.109221	Structured	0.040732	Uncertain	0.970	0.223	0.000											-6.636	Likely Benign	0.398	Ambiguous	Likely Benign	1.24	Ambiguous	0.0	1.06	Ambiguous	1.15	Ambiguous	0.80	Ambiguous	0.182	Likely Benign	-0.80	Neutral	0.969	Probably Damaging	0.960	Probably Damaging	3.33	Benign	0.13	Tolerated			0.1003	0.2891		4	3	-0.3	-14.03
c.2118A>C	E706D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E706D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments likewise support a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. **Thus, the variant is most likely benign, and this prediction does not contradict any ClinVar status (none is available).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000											-4.216	Likely Benign	0.087	Likely Benign	Likely Benign	0.22	Likely Benign	0.0	0.02	Likely Benign	0.12	Likely Benign	-0.16	Likely Benign	0.182	Likely Benign	-0.01	Neutral	0.000	Benign	0.000	Benign	4.17	Benign	0.41	Tolerated			0.1681	0.2726		3	2	0.0	-14.03
c.2118A>T	E706D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E706D is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts pathogenicity. High‑accuracy assessments further support a benign effect: AlphaMissense‑Optimized predicts benign, the SGM Consensus indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. With all evidence pointing to a neutral impact and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.200174	Structured	0.377033	Uncertain	0.929	0.363	0.000											-4.216	Likely Benign	0.087	Likely Benign	Likely Benign	0.22	Likely Benign	0.0	0.02	Likely Benign	0.12	Likely Benign	-0.16	Likely Benign	0.182	Likely Benign	-0.01	Neutral	0.000	Benign	0.000	Benign	4.17	Benign	0.41	Tolerated			0.1681	0.2726		3	2	0.0	-14.03
c.2149C>A	L717I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome, while premPS is inconclusive. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) reports Benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-4.836	Likely Benign	0.168	Likely Benign	Likely Benign	0.27	Likely Benign	0.0	0.33	Likely Benign	0.30	Likely Benign	-0.73	Ambiguous	0.182	Likely Benign	0.60	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.43	Benign	1.00	Tolerated			0.0712	0.2570		2	2	0.7	0.00
c.2416T>A	F806I 2D AIThe SynGAP1 missense variant F806I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the balance of evidence from the consensus of prediction algorithms points to a pathogenic impact for F806I. This conclusion is not contradicted by ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-5.040	Likely Benign	0.744	Likely Pathogenic	Likely Benign										0.182	Likely Benign	-3.19	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	2.15	Pathogenic	0.03	Affected			0.2583	0.1357		1	0	1.7	-34.02
c.2603A>T	D868V 2D AIThe SynGAP1 missense variant D868V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, and ESM1b, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250											-5.200	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.182	Likely Benign	-3.17	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.49	Pathogenic	0.25	Tolerated			0.1485	0.6753		-2	-3	7.7	-15.96
c.2683A>T	S895C 2D AIThe SynGAP1 missense variant S895C is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. 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											-8.006	Likely Pathogenic	0.259	Likely Benign	Likely Benign										0.182	Likely Benign	-2.44	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.60	Benign	0.08	Tolerated			0.1072	0.6350		0	-1	3.3	16.06
c.2693C>A	S898Y 2D AISynGAP1 missense variant S898Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools and the consensus prediction indicate a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500											-5.927	Likely Benign	0.712	Likely Pathogenic	Likely Benign										0.182	Likely Benign	-2.69	Deleterious	0.998	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.00	Affected			0.1244	0.6838		-3	-2	-0.5	76.10
c.2787C>A	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2787C>G	N929K 2D AIThe SynGAP1 missense variant N929K is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign—REVEL—and pathogenic—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic status; Foldetta results are not available. Taken together, the preponderance of evidence supports a pathogenic interpretation for N929K, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.986867	Binding	0.321	0.851	0.375											-10.041	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.182	Likely Benign	-4.35	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.48	Pathogenic	0.00	Affected			0.2098	0.6046		1	0	-0.4	14.07
c.2791C>G	L931V 2D AIThe SynGAP1 missense variant L931V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for the L931V variant, and this conclusion does not contradict any ClinVar annotation, as none exists for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375											-1.512	Likely Benign	0.234	Likely Benign	Likely Benign										0.182	Likely Benign	0.71	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	3.03	Benign	0.70	Tolerated			0.1690	0.3164		2	1	0.4	-14.03
c.2877C>A	H959Q 2D AIThe SynGAP1 missense variant H959Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely benign. Only ESM1b predicts a pathogenic outcome, representing the sole discordant signal. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that H959Q is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.980566	Binding	0.333	0.905	0.750											-8.657	Likely Pathogenic	0.126	Likely Benign	Likely Benign										0.182	Likely Benign	-0.77	Neutral	0.255	Benign	0.105	Benign	4.15	Benign	0.10	Tolerated			0.2264	0.3936		3	0	-0.3	-9.01
c.2877C>G	H959Q 2D AIThe SynGAP1 missense variant H959Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while the single pathogenic prediction comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that H959Q is most likely benign, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.980566	Binding	0.333	0.905	0.750											-8.657	Likely Pathogenic	0.126	Likely Benign	Likely Benign										0.182	Likely Benign	-0.77	Neutral	0.255	Benign	0.105	Benign	4.15	Benign	0.10	Tolerated			0.2264	0.3936		3	0	-0.3	-9.01
c.2896C>G	H966D 2D AIThe SynGAP1 missense variant H966D is listed in gnomAD (ID 6‑33443448‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign or likely benign. Only two tools predict a damaging outcome—polyPhen‑2 HumDiv and ESM1b—which are outliers relative to the consensus. High‑accuracy assessments confirm the benign trend: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus also indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions support a benign impact, and this is consistent with the absence of a pathogenic ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.976962	Disordered	0.974672	Binding	0.378	0.879	0.750								6-33443448-C-G	1	6.20e-7	-8.426	Likely Pathogenic	0.201	Likely Benign	Likely Benign										0.182	Likely Benign	-1.09	Neutral	0.494	Possibly Damaging	0.170	Benign	4.05	Benign	0.93	Tolerated	4.32	2	0.2504	0.3066		-1	1	-0.3	-22.05
c.299A>C	Y100S 2D AIThe SynGAP1 missense variant Y100S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.675421	Binding	0.341	0.880	0.625											-1.217	Likely Benign	0.129	Likely Benign	Likely Benign										0.182	Likely Benign	-0.14	Neutral	0.675	Possibly Damaging	0.175	Benign	4.31	Benign	0.00	Affected			0.5066	0.1600	Weaken	-3	-2	0.5	-76.10
c.3211G>T	G1071C 2D AIThe SynGAP1 missense variant G1071C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy predictions—supports a benign classification, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983740	Binding	0.313	0.905	0.875											-5.364	Likely Benign	0.305	Likely Benign	Likely Benign										0.182	Likely Benign	-2.16	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	4.01	Benign	0.00	Affected			0.1323	0.4227		-3	-3	2.9	46.09
c.3266G>T	G1089V 2D AIThe SynGAP1 missense variant G1089V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for G1089V. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000											-4.809	Likely Benign	0.527	Ambiguous	Likely Benign										0.182	Likely Benign	-2.81	Deleterious	0.984	Probably Damaging	0.722	Possibly Damaging	2.40	Pathogenic	0.00	Affected			0.1326	0.4413		-1	-3	4.6	42.08
c.493A>G	S165G 2D AIThe SynGAP1 missense variant S165G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-7.691	In-Between	0.223	Likely Benign	Likely Benign										0.182	Likely Benign	-1.17	Neutral	0.272	Benign	0.086	Benign	3.99	Benign	0.00	Affected			0.2622	0.4441		1	0	0.4	-30.03
c.62T>C	F21S 2D AIThe SynGAP1 missense variant F21S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500											-2.396	Likely Benign	0.745	Likely Pathogenic	Likely Benign										0.182	Likely Benign	-0.22	Neutral	0.462	Possibly Damaging	0.307	Benign	4.15	Benign	0.00	Affected			0.4793	0.1133		-3	-2	-3.6	-60.10
c.1557A>C	E519D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven benign predictions versus six pathogenic ones, the overall evidence slightly favors a benign classification. This conclusion does not contradict the ClinVar status, which contains no pathogenic assertion for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.009	Likely Pathogenic	0.723	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.0	0.40	Likely Benign	0.32	Likely Benign	0.05	Likely Benign	0.183	Likely Benign	-2.62	Deleterious	0.989	Probably Damaging	0.979	Probably Damaging	3.31	Benign	0.07	Tolerated			0.2088	0.1824		3	2	0.0	-14.03
c.160A>T	N54Y 2D AIThe SynGAP1 missense variant N54Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). High‑accuracy methods show AlphaMissense‑Optimized as benign; the SGM Consensus is unavailable, and Foldetta results are not provided, so its stability prediction is also unavailable. Overall, more tools (five) predict pathogenicity than benign (four), and the high‑accuracy benign prediction is outweighed by the majority of pathogenic calls. Thus, the variant is most likely pathogenic based on current computational 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.			0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000											-9.313	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-1.57	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.16	Benign	0.00	Affected			0.0512	0.6687		-2	-2	2.2	49.07
c.2115G>C	K705N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705N is listed in ClinVar (ID 872011.0) as Pathogenic and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, Rosetta, premPS, FATHMM) and pathogenic predictions (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default). Uncertain results come from FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is inconclusive, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic, and Foldetta also yields an uncertain stability change. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, which aligns with its ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000					Likely Pathogenic		1				-9.767	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.0	0.37	Likely Benign	0.56	Ambiguous	0.44	Likely Benign	0.183	Likely Benign	-3.12	Deleterious	0.996	Probably Damaging	0.876	Possibly Damaging	3.37	Benign	0.02	Affected	3.47	10	0.2480	0.1124		1	0	0.4	-14.07	221.4	-20.2	0.0	0.0	0.0	0.1						X		Uncertain	The amino side chain of Lys705, located at the end and outer surface of an α-helix (res. Thr704-Gly712), does not form any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Asn705 briefly forms a salt bridge with Glu706. However, there is no apparent difference between the systems. Due to the model ending abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2115G>T	K705N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K705N is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Three tools (FoldX, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further support a pathogenic interpretation: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic”; AlphaMissense‑Optimized remains uncertain, and Foldetta is also uncertain. Overall, the balance of evidence favors a pathogenic effect for K705N, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.767	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.0	0.37	Likely Benign	0.56	Ambiguous	0.44	Likely Benign	0.183	Likely Benign	-3.12	Deleterious	0.996	Probably Damaging	0.876	Possibly Damaging	3.37	Benign	0.02	Affected	3.47	10	0.2480	0.1124		1	0	0.4	-14.07	221.4	-20.2	0.0	0.0	0.0	0.1						X		Uncertain	The amino side chain of Lys705, located at the end and outer surface of an α-helix (res. Thr704-Gly712), does not form any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Asn705 briefly forms a salt bridge with Glu706. However, there is no apparent difference between the systems. Due to the model ending abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2128A>C	K710Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K710Q missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The high‑accuracy AlphaMissense‑Optimized score classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (pathogenic), FATHMM (benign), and PROVEAN (pathogenic)—indicates pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts a benign effect. Overall, the majority of evidence points to a benign impact, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-8.920	Likely Pathogenic	0.372	Ambiguous	Likely Benign	0.12	Likely Benign	0.0	0.02	Likely Benign	0.07	Likely Benign	0.49	Likely Benign	0.183	Likely Benign	-3.58	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.39	Benign	0.01	Affected			0.3043	0.1214		1	1	0.4	-0.04
c.212A>T	D71V 2D AIThe SynGAP1 D71V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign classification (3 benign vs. 1 pathogenic votes). High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.456046	Uncertain	0.350	0.799	0.375											-3.549	Likely Benign	0.780	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-2.28	Neutral	0.334	Benign	0.060	Benign	4.01	Benign	0.00	Affected			0.0771	0.6197		-2	-3	7.7	-15.96
c.2173C>G	L725V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The remaining methods (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) are inconclusive. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta provides no definitive stability change. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625											-8.291	Likely Pathogenic	0.461	Ambiguous	Likely Benign	1.76	Ambiguous	0.1	1.87	Ambiguous	1.82	Ambiguous	0.77	Ambiguous	0.183	Likely Benign	-2.69	Deleterious	0.993	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.01	Affected			0.1739	0.3977		2	1	0.4	-14.03
c.2254T>C	S752P 2D AIThe SynGAP1 missense variant S752P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for S752P, and this conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.690594	Binding	0.365	0.877	0.625											-3.491	Likely Benign	0.158	Likely Benign	Likely Benign										0.183	Likely Benign	-1.09	Neutral	0.998	Probably Damaging	0.912	Probably Damaging	1.51	Pathogenic	0.02	Affected			0.2288	0.5882		1	-1	-0.8	10.04
c.2318T>G	M773R 2D AIThe SynGAP1 missense variant M773R is listed in gnomAD (ID 6‑33442476‑T‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are 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 further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250								6-33442476-T-G	1	1.28e-6	-4.340	Likely Benign	0.597	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-1.87	Neutral	0.220	Benign	0.471	Possibly Damaging	4.18	Benign	0.02	Affected	3.64	6	0.1778	0.0800		-1	0	-6.4	24.99
c.2461T>C	C821R 2D AIThe SynGAP1 missense variant C821R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (six out of nine) indicate a pathogenic impact, while three suggest benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-3.997	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			0.1944	0.1746		-4	-3	-7.0	53.05
c.248G>T	R83I 2D AIThe SynGAP1 missense variant R83I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of evidence (seven pathogenic vs. three benign predictions) indicates that R83I is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.637480	Disordered	0.522784	Binding	0.275	0.895	0.250											-4.021	Likely Benign	0.998	Likely Pathogenic	Likely Pathogenic										0.183	Likely Benign	-3.15	Deleterious	0.972	Probably Damaging	0.766	Possibly Damaging	3.17	Benign	0.00	Affected			0.1450	0.3219		-2	-3	9.0	-43.03
c.2522T>C	V841A 2D AIThe SynGAP1 missense variant V841A (ClinVar ID 1395978.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443074‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool reports an uncertain outcome, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie (two pathogenic, two benign) and is therefore inconclusive. No Foldetta stability assessment is available for this variant. Overall, the balance of evidence favors a pathogenic interpretation, which does not contradict the current ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.616495	Binding	0.261	0.873	0.125					Uncertain		1	6-33443074-T-C	3	1.86e-6	-8.152	Likely Pathogenic	0.901	Likely Pathogenic	Ambiguous										0.183	Likely Benign	-2.13	Neutral	0.992	Probably Damaging	0.989	Probably Damaging	2.57	Benign	0.02	Affected	3.77	5	0.3069	0.2106		0	0	-2.4	-28.05
c.2561G>A	R854H 2D AIThe SynGAP1 missense variant R854H is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443113‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.488780	Uncertain	0.277	0.815	0.750					Uncertain		1	6-33443113-G-A	4	2.48e-6	-3.686	Likely Benign	0.094	Likely Benign	Likely Benign										0.183	Likely Benign	-1.38	Neutral	0.997	Probably Damaging	0.899	Possibly Damaging	4.07	Benign	0.04	Affected	3.88	3	0.3103	0.2202		2	0	1.3	-19.05
c.2897A>T	H966L 2D AIThe SynGAP1 missense variant H966L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No pathogenic predictions are present among the evaluated algorithms. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) reports likely benign. Foldetta results are not available for this variant. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.976962	Disordered	0.974672	Binding	0.378	0.879	0.750											-6.119	Likely Benign	0.095	Likely Benign	Likely Benign										0.183	Likely Benign	-1.74	Neutral	0.174	Benign	0.062	Benign	4.05	Benign	0.35	Tolerated			0.1514	0.5316		-2	-3	7.0	-23.98
c.298T>A	Y100N 2D AIThe SynGAP1 missense variant Y100N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.675421	Binding	0.341	0.880	0.625											-2.579	Likely Benign	0.109	Likely Benign	Likely Benign										0.183	Likely Benign	-0.66	Neutral	0.675	Possibly Damaging	0.099	Benign	4.23	Benign	0.00	Affected			0.2487	0.0373		-2	-2	-2.2	-49.07
c.3065T>G	L1022R 2D AIThe SynGAP1 missense variant L1022R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L1022R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500											-2.875	Likely Benign	0.659	Likely Pathogenic	Likely Benign										0.183	Likely Benign	-1.96	Neutral	0.986	Probably Damaging	0.894	Possibly Damaging	2.51	Benign	0.01	Affected			0.1279	0.1387		-3	-2	-8.3	43.03
c.3209G>T	R1070M 2D AIThe SynGAP1 missense variant R1070M 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 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 as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus benign call and the absence of pathogenic predictions from the most reliable tools, suggests the variant is most likely benign. 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		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875											-6.455	Likely Benign	0.917	Likely Pathogenic	Ambiguous										0.183	Likely Benign	-2.27	Neutral	0.995	Probably Damaging	0.907	Possibly Damaging	3.74	Benign	0.00	Affected			0.1661	0.4324		0	-1	6.4	-24.99
c.3227T>G	L1076W 2D AIThe SynGAP1 missense variant L1076W is not 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 predict 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 interpretation. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.989617	Binding	0.301	0.892	0.750											-6.377	Likely Benign	0.822	Likely Pathogenic	Ambiguous										0.183	Likely Benign	-1.40	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	2.38	Pathogenic	0.02	Affected			0.0749	0.3740		-2	-2	-4.7	73.05
c.3350G>C	G1117A 2D AIThe SynGAP1 missense variant G1117A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750											-6.514	Likely Benign	0.082	Likely Benign	Likely Benign										0.183	Likely Benign	-0.41	Neutral	0.152	Benign	0.071	Benign	4.61	Benign	0.23	Tolerated			0.3545	0.4944		1	0	2.2	14.03
c.3427A>C	T1143P 2D AIThe SynGAP1 missense variant T1143P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic effect. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.722918	Binding	0.275	0.837	1.000											-2.307	Likely Benign	0.155	Likely Benign	Likely Benign										0.183	Likely Benign	0.80	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.69	Benign	0.24	Tolerated			0.1818	0.4108		0	-1	-0.9	-3.99
c.3598G>C	E1200Q 2D AIThe SynGAP1 missense variant E1200Q is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available, so these do not influence the overall interpretation. High‑accuracy assessments—AlphaMissense‑Optimized (benign) and SGM‑Consensus (likely benign)—support a benign classification. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-4.411	Likely Benign	0.464	Ambiguous	Likely Benign										0.183	Likely Benign	0.14	Neutral	0.994	Probably Damaging	0.946	Probably Damaging	2.84	Benign	0.30	Tolerated			0.0767	0.4012		2	2	0.0	-0.98
c.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.3751C>G	Q1251E 2D AIThe SynGAP1 missense variant Q1251E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two uncertain and two benign calls, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875											-7.836	In-Between	0.499	Ambiguous	Likely Benign										0.183	Likely Benign	-2.26	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.50	Benign	0.00	Affected			0.1281	0.1266		2	2	0.0	0.98
c.41C>G	P14R 2D AIThe SynGAP1 missense variant P14R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus methods give a benign verdict: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No result is available from Foldetta, so its folding‑stability assessment is not considered. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of any 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		0.433034	Structured	0.471596	Uncertain	0.399	0.909	0.375											-2.794	Likely Benign	0.253	Likely Benign	Likely Benign										0.183	Likely Benign	0.13	Neutral	0.486	Possibly Damaging	0.032	Benign	4.20	Benign	0.00	Affected			0.1597	0.3536		0	-2	-2.9	59.07
c.973C>G	L325V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L325V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Rosetta and Foldetta give uncertain results. The high‑accuracy consensus from AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta remains uncertain. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.352862	Structured	0.424577	Uncertain	0.955	0.436	0.000											-3.104	Likely Benign	0.162	Likely Benign	Likely Benign	2.26	Destabilizing	0.1	1.27	Ambiguous	1.77	Ambiguous	-0.39	Likely Benign	0.183	Likely Benign	0.16	Neutral	0.898	Possibly Damaging	0.472	Possibly Damaging	1.68	Pathogenic	1.00	Tolerated			0.1571	0.3957		2	1	0.4	-14.03
c.1003C>A	R335S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, premPS, and SIFT; pathogenic predictions from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, 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 labeled Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No evidence from FoldX or Rosetta alone is available. Based on the preponderance of pathogenic predictions and the high‑accuracy tools, the variant is most likely pathogenic, which is consistent with the absence of ClinVar reporting and gnomAD data. 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											-9.286	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.68	Ambiguous	0.1	0.72	Ambiguous	0.70	Ambiguous	0.14	Likely Benign	0.184	Likely Benign	-3.30	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.89	Pathogenic	0.11	Tolerated			0.2598	0.4005		0	-1	3.7	-69.11
c.1274C>G	T425S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425S is not 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, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, Rosetta) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (five benign vs. four pathogenic) lean toward a benign interpretation, and this assessment 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.		GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-7.420	In-Between	0.676	Likely Pathogenic	Likely Benign	0.22	Likely Benign	0.1	0.77	Ambiguous	0.50	Ambiguous	0.63	Ambiguous	0.184	Likely Benign	-3.05	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.42	Benign	0.07	Tolerated			0.2511	0.2324		1	1	-0.1	-14.03
c.165G>C	Q55H 2D AIThe SynGAP1 missense variant Q55H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-5.624	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.76	Neutral	0.676	Possibly Damaging	0.585	Possibly Damaging	3.81	Benign	0.00	Affected			0.1352	0.4143		3	0	0.3	9.01
c.165G>T	Q55H 2D AIThe SynGAP1 missense variant Q55H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000											-5.624	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.76	Neutral	0.676	Possibly Damaging	0.585	Possibly Damaging	3.81	Benign	0.00	Affected			0.1352	0.4143		3	0	0.3	9.01
c.1701G>C	E567D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567D missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points toward 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	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-8.276	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.1	1.94	Ambiguous	1.41	Ambiguous	0.70	Ambiguous	0.184	Likely Benign	-2.72	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.21	Tolerated			0.1602	0.3426		3	2	0.0	-14.03
c.1701G>T	E567D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E567D missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain or unavailable results come from FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta’s stability prediction is inconclusive. Overall, the majority of pathogenic predictions outweigh the benign ones, suggesting the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.021816	Structured	0.051008	Uncertain	0.916	0.234	0.000											-8.276	Likely Pathogenic	0.575	Likely Pathogenic	Likely Benign	0.87	Ambiguous	0.1	1.94	Ambiguous	1.41	Ambiguous	0.70	Ambiguous	0.184	Likely Benign	-2.72	Deleterious	0.996	Probably Damaging	0.989	Probably Damaging	3.41	Benign	0.21	Tolerated			0.1602	0.3426		3	2	0.0	-14.03
c.2011G>A	D671N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D671N is reported in gnomAD (6‑33441270‑G‑A) but has no ClinVar entry. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus remains pathogenic. Overall, the predictions are split, with a slight bias toward benign outcomes from the majority of tools, but the consensus pathogenic signal from SGM and several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of benign predictions, and this 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	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000								6-33441270-G-A			-10.347	Likely Pathogenic	0.685	Likely Pathogenic	Likely Benign	0.18	Likely Benign	0.1	0.39	Likely Benign	0.29	Likely Benign	0.19	Likely Benign	0.184	Likely Benign	-3.19	Deleterious	0.887	Possibly Damaging	0.592	Possibly Damaging	3.36	Benign	0.02	Affected	3.39	27	0.1298	0.6463		1	2	0.0	-0.98
c.2303A>G	D768G 2D AIThe SynGAP1 D768G missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all predict benign, whereas AlphaMissense‑Default predicts pathogenic. The high‑accuracy AlphaMissense‑Optimized result is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, which would provide a protein‑folding stability assessment, has no available output for this variant. Overall, the preponderance of evidence points to a benign effect, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.332115	Structured	0.928237	Binding	0.314	0.877	0.250											-7.150	In-Between	0.697	Likely Pathogenic	Likely Benign										0.184	Likely Benign	0.03	Neutral	0.393	Benign	0.131	Benign	4.09	Benign	0.72	Tolerated			0.4130	0.7476		1	-1	3.1	-58.04
c.2483C>G	T828R 2D AIThe SynGAP1 missense variant T828R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T828R, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500											-4.887	Likely Benign	0.773	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.38	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.64	Benign	0.47	Tolerated			0.0815	0.2530		-1	-1	-3.8	55.08
c.2506A>T	S836C 2D AIThe SynGAP1 missense variant S836C 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT; ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.634582	Binding	0.269	0.859	0.250											-7.859	In-Between	0.208	Likely Benign	Likely Benign										0.184	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.923	Probably Damaging	2.50	Benign	0.04	Affected			0.0834	0.5468		0	-1	3.3	16.06
c.2552C>A	P851H 2D AIThe SynGAP1 missense variant P851H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.526893	Binding	0.347	0.819	0.625											-4.730	Likely Benign	0.102	Likely Benign	Likely Benign										0.184	Likely Benign	0.19	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	4.18	Benign	0.15	Tolerated			0.1577	0.5378		0	-2	-1.6	40.02
c.2725A>C	M909L 2D AIThe SynGAP1 missense variant M909L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions points to a benign effect, and this is consistent with the lack of a ClinVar classification—there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250											-1.417	Likely Benign	0.152	Likely Benign	Likely Benign										0.184	Likely Benign	-0.85	Neutral	0.002	Benign	0.006	Benign	2.82	Benign	0.32	Tolerated	3.77	5	0.1591	0.4352		2	4	1.9	-18.03
c.2725A>T	M909L 2D AIThe SynGAP1 missense variant M909L is catalogued in gnomAD (ID 6‑33443277‑A‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions is benign, 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		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250								6-33443277-A-T	4	2.48e-6	-1.417	Likely Benign	0.152	Likely Benign	Likely Benign										0.184	Likely Benign	-0.85	Neutral	0.002	Benign	0.006	Benign	2.82	Benign	0.32	Tolerated	3.77	5	0.1591	0.4352		2	4	1.9	-18.03
c.2740G>C	D914H 2D AIThe SynGAP1 missense variant D914H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) support a benign classification. This consensus does not contradict ClinVar status, as no ClinVar entry exists for this variant. Thus, based on current computational evidence, the D914H variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250											-3.755	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.26	Neutral	1.000	Probably Damaging	0.993	Probably Damaging	2.74	Benign	0.01	Affected			0.1963	0.8451		1	-1	0.3	22.05
c.3063G>C	Q1021H 2D AIThe SynGAP1 missense variant Q1021H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, as no ClinVar status is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500											-4.694	Likely Benign	0.664	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.72	Neutral	0.996	Probably Damaging	0.995	Probably Damaging	2.61	Benign	0.01	Affected			0.1211	0.3601		3	0	0.3	9.01
c.3063G>T	Q1021H 2D AIThe SynGAP1 missense variant Q1021H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500											-4.694	Likely Benign	0.664	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.72	Neutral	0.996	Probably Damaging	0.995	Probably Damaging	2.61	Benign	0.01	Affected			0.1211	0.3601		3	0	0.3	9.01
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.323A>G	K108R 2D AIThe SynGAP1 missense variant K108R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33432188‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875					Uncertain		1	6-33432188-A-G	6	3.72e-6	-2.892	Likely Benign	0.148	Likely Benign	Likely Benign										0.184	Likely Benign	0.37	Neutral	0.993	Probably Damaging	0.956	Probably Damaging	4.22	Benign	1.00	Tolerated	3.61	5	0.5286	0.1229	Weaken	3	2	-0.6	28.01
c.3575T>G	L1192R 2D AIThe SynGAP1 missense variant L1192R is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-3.221	Likely Benign	0.695	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.33	Neutral	0.992	Probably Damaging	0.940	Probably Damaging	2.75	Benign	0.35	Tolerated			0.1148	0.0558		-3	-2	-8.3	43.03
c.3698T>G	I1233S 2D AIThe SynGAP1 missense variant I1233S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and FATHMM, whereas the majority of other predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus likewise indicates likely pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.564054	Binding	0.881	0.531	0.125											-8.066	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.184	Likely Benign	-3.60	Deleterious	0.946	Possibly Damaging	0.673	Possibly Damaging	2.53	Benign	0.00	Affected			0.2848	0.0910		-1	-2	-5.3	-26.08
c.491G>A	R164Q 2D AISynGAP1 missense variant R164Q is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33432788‑G‑A). Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta results are not available. Overall, the balance of evidence slightly favors a benign interpretation, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.512396	Binding	0.317	0.666	0.250					Uncertain		1	6-33432788-G-A	2	1.24e-6	-11.208	Likely Pathogenic	0.600	Likely Pathogenic	Likely Benign										0.184	Likely Benign	-1.86	Neutral	0.957	Probably Damaging	0.342	Benign	3.82	Benign	0.00	Affected	3.74	4	0.3607	0.2711		1	1	1.0	-28.06
c.529T>C	F177L 2D AIThe SynGAP1 missense variant F177L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence (seven benign predictions versus two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.461817	Uncertain	0.357	0.598	0.500											-5.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.184	Likely Benign	0.24	Neutral	0.022	Benign	0.022	Benign	4.41	Benign	1.00	Tolerated			0.2376	0.4280		2	0	1.0	-34.02
c.1274C>A	T425N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T425N 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, and AlphaMissense‑Default. Predictions labeled uncertain (Foldetta, premPS, AlphaMissense‑Optimized, Rosetta) are treated as unavailable. High‑accuracy assessments further indicate a likely pathogenic outcome from the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and an uncertain result from AlphaMissense‑Optimized and Foldetta. Overall, the majority of definitive predictions support a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.401218	Uncertain	0.964	0.280	0.000											-10.709	Likely Pathogenic	0.925	Likely Pathogenic	Ambiguous	0.19	Likely Benign	0.1	0.81	Ambiguous	0.50	Ambiguous	0.82	Ambiguous	0.185	Likely Benign	-3.87	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.44	Benign	0.04	Affected			0.1169	0.2843		0	0	-2.8	13.00
c.1598C>G	A533G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533G resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome; Rosetta is uncertain and therefore not counted as evidence. High‑accuracy assessments—all of which are available—show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta as Benign, reinforcing the benign consensus. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000											-3.412	Likely Benign	0.122	Likely Benign	Likely Benign	0.32	Likely Benign	0.1	0.64	Ambiguous	0.48	Likely Benign	0.33	Likely Benign	0.185	Likely Benign	-1.94	Neutral	0.258	Benign	0.099	Benign	-1.23	Pathogenic	0.23	Tolerated			0.2348	0.4737		1	0	-2.2	-14.03
c.2609T>A	L870Q 2D AIThe SynGAP1 missense variant L870Q is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as benign, and the SGM‑Consensus itself is labeled likely benign. No output is available from the Foldetta stability analysis, so it does not influence the overall assessment. Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.688079	Binding	0.274	0.850	0.125											-4.029	Likely Benign	0.417	Ambiguous	Likely Benign										0.185	Likely Benign	-1.90	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	2.63	Benign	0.02	Affected			0.1027	0.1003		-2	-2	-7.3	14.97
c.2852A>G	H951R 2D AIThe SynGAP1 missense variant H951R is listed in ClinVar as Pathogenic (ClinVar ID 1003739.0) and is not reported in gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Based on the collective predictions, the variant is most likely benign, which contradicts its ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.901477	Binding	0.415	0.925	0.750					Likely Pathogenic		1				-4.964	Likely Benign	0.125	Likely Benign	Likely Benign										0.185	Likely Benign	-1.08	Neutral	0.048	Benign	0.029	Benign	5.46	Benign	0.24	Tolerated	3.77	5	0.2808	0.3220		2	0	-1.3	19.05
c.3257C>A	P1086Q 2D AIThe SynGAP1 missense variant P1086Q is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33443809‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (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 predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000								6-33443809-C-A			-4.668	Likely Benign	0.652	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-2.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.77	Benign	0.00	Affected	3.77	5	0.1285	0.4784		-1	0	-1.9	31.01
c.3505G>A	E1169K 2D AISynGAP1 missense variant E1169K is listed in gnomAD (ID 6‑33444540‑G‑A) but has no ClinVar record. Functional prediction tools fall into two groups: benign predictions come from SGM‑Consensus, REVEL, PROVEAN, ESM1b, and FATHMM; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign. Foldetta stability analysis is unavailable. Overall, the evidence is split evenly, with one high‑accuracy tool supporting pathogenicity and the consensus tool supporting benignity. Therefore, the variant’s impact remains uncertain; it is not contradicted by ClinVar status, which has no entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625								6-33444540-G-A	1	6.20e-7	-3.335	Likely Benign	0.973	Likely Pathogenic	Likely Pathogenic										0.185	Likely Benign	-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.3746G>C	R1249T 2D AIThe SynGAP1 missense variant R1249T is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The SGM‑Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence (10 pathogenic vs. 2 benign predictions) points to a pathogenic impact for R1249T. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-8.014	Likely Pathogenic	0.712	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-4.59	Deleterious	0.990	Probably Damaging	0.903	Possibly Damaging	1.71	Pathogenic	0.00	Affected			0.1646	0.2458		-1	-1	3.8	-55.08
c.3862A>G	K1288E 2D AISynGAP1 missense variant K1288E is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33447910‑A‑G). Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this change. Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a clear benign classification. Thus, the variant is most likely pathogenic, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625					Uncertain		1	6-33447910-A-G	5	3.22e-6	-2.751	Likely Benign	0.407	Ambiguous	Likely Benign										0.185	Likely Benign	-3.27	Deleterious	0.979	Probably Damaging	0.973	Probably Damaging	2.13	Pathogenic	0.00	Affected	3.77	5	0.3627	0.0676		1	0	0.4	0.94
c.440A>T	Q147L 2D AIThe SynGAP1 missense variant Q147L 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default; the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points toward a pathogenic interpretation, and this is not contradicted by any ClinVar classification because none exists. 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											-9.879	Likely Pathogenic	0.740	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-3.51	Deleterious	0.079	Benign	0.037	Benign	3.92	Benign	0.03	Affected			0.0861	0.4927		-2	-2	7.3	-14.97
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.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.47T>A	M16K 2D AIThe SynGAP1 missense variant M16K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational predictions and the high‑accuracy consensus suggest that M16K is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375											-2.567	Likely Benign	0.635	Likely Pathogenic	Likely Benign										0.185	Likely Benign	-0.37	Neutral	0.003	Benign	0.001	Benign	4.23	Benign	0.00	Affected			0.1984	0.1112		0	-1	-5.8	-3.02
c.525A>C	Q175H 2D AIThe SynGAP1 missense variant Q175H 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. 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” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-6.635	Likely Benign	0.824	Likely Pathogenic	Ambiguous										0.185	Likely Benign	-1.52	Neutral	0.875	Possibly Damaging	0.459	Possibly Damaging	4.09	Benign	0.10	Tolerated			0.1273	0.3411		3	0	0.3	9.01
c.525A>T	Q175H 2D AIThe SynGAP1 missense variant Q175H 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 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” and the SGM‑Consensus as “Likely Benign”; no Foldetta stability data are available. Overall, the balance of evidence favors a benign classification, 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		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-6.635	Likely Benign	0.824	Likely Pathogenic	Ambiguous										0.185	Likely Benign	-1.52	Neutral	0.875	Possibly Damaging	0.459	Possibly Damaging	4.09	Benign	0.10	Tolerated			0.1273	0.3411		3	0	0.3	9.01
c.64A>G	R22G 2D AIThe SynGAP1 missense variant R22G is reported in ClinVar as “Not submitted” and is present in gnomAD (ID 6‑33420328‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.441505	Uncertain	0.377	0.891	0.500								6-33420328-A-G			-3.628	Likely Benign	0.322	Likely Benign	Likely Benign										0.185	Likely Benign	-0.42	Neutral	0.462	Possibly Damaging	0.152	Benign	4.19	Benign	0.00	Affected	4.32	1	0.3590	0.4098		-2	-3	4.1	-99.14
c.1008G>C	K336N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K336N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, and polyPhen‑2 HumVar, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus also predicts likely pathogenic, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. No prediction or stability result is missing. Overall, the majority of tools and the high‑accuracy methods lean toward pathogenicity, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status because ClinVar has no entry. 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											-13.307	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	-0.02	Likely Benign	0.09	Likely Benign	0.20	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.801	Possibly Damaging	0.315	Benign	1.59	Pathogenic	0.01	Affected			0.3710	0.1599		1	0	0.4	-14.07
c.1008G>T	K336N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K336N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate 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. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, 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 majority of evidence points toward a pathogenic impact for K336N, 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											-13.307	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.1	-0.02	Likely Benign	0.09	Likely Benign	0.20	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.801	Possibly Damaging	0.315	Benign	1.59	Pathogenic	0.01	Affected			0.3710	0.1599		1	0	0.4	-14.07
c.1129A>T	M377L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377L is reported in gnomAD (variant ID 6‑33438034‑A‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus all classify the change as benign or likely benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a benign effect. No inconclusive or missing predictions are present. Based on the collective evidence, the variant is most likely benign, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.675549	Disordered	0.431183	Uncertain	0.324	0.884	0.625								6-33438034-A-T			-2.394	Likely Benign	0.082	Likely Benign	Likely Benign	0.13	Likely Benign	0.1	0.69	Ambiguous	0.41	Likely Benign	0.16	Likely Benign	0.186	Likely Benign	-0.32	Neutral	0.000	Benign	0.001	Benign	5.46	Benign	0.58	Tolerated	4.32	12	0.2516	0.4885		2	4	1.9	-18.03
c.1985A>T	Q662L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q662L is not 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, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen2_HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen2_HumDiv, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Overall, the majority of evidence supports a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.046336	Structured	0.103446	Uncertain	0.932	0.323	0.000											-10.291	Likely Pathogenic	0.300	Likely Benign	Likely Benign	0.04	Likely Benign	0.0	0.12	Likely Benign	0.08	Likely Benign	0.17	Likely Benign	0.186	Likely Benign	-4.09	Deleterious	0.699	Possibly Damaging	0.057	Benign	3.42	Benign	0.10	Tolerated			0.1070	0.5255		-2	-2	7.3	-14.97
c.2023A>C	N675H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. Predictions that are inconclusive are Foldetta and premPS. High‑accuracy methods give a benign result from AlphaMissense‑Optimized, a benign consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and an uncertain result from Foldetta. Taken together, the majority of evidence points to a benign impact, and this does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000											-5.593	Likely Benign	0.254	Likely Benign	Likely Benign	3.06	Destabilizing	1.1	-0.16	Likely Benign	1.45	Ambiguous	0.56	Ambiguous	0.186	Likely Benign	-2.62	Deleterious	0.999	Probably Damaging	0.929	Probably Damaging	3.39	Benign	0.04	Affected			0.1478	0.7478		2	1	0.3	23.04
c.2419T>G	Y807D 2D AIThe SynGAP1 missense variant Y807D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, while the majority of algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Uncertain calls come from ESM1b and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for Y807D, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-7.598	In-Between	0.862	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-4.40	Deleterious	0.966	Probably Damaging	0.773	Possibly Damaging	2.42	Pathogenic	0.00	Affected			0.3944	0.0704		-4	-3	-2.2	-48.09
c.2776T>G	S926A 2D AIThe SynGAP1 missense variant S926A is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of reliable predictions indicate a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-3.042	Likely Benign	0.463	Ambiguous	Likely Benign										0.186	Likely Benign	-2.13	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.59	Pathogenic	0.00	Affected			0.4657	0.4488		1	1	2.6	-16.00
c.2851C>G	H951D 2D AIThe SynGAP1 missense variant H951D is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated methods. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.901477	Binding	0.415	0.925	0.750											-5.901	Likely Benign	0.188	Likely Benign	Likely Benign										0.186	Likely Benign	-0.33	Neutral	0.000	Benign	0.001	Benign	5.43	Benign	0.46	Tolerated			0.2851	0.2475		1	-1	-0.3	-22.05
c.3398T>G	I1133S 2D AIThe SynGAP1 missense variant I1133S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) is likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective evidence strongly supports a benign impact for I1133S, 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		0.919029	Disordered	0.832785	Binding	0.316	0.892	0.750											-4.034	Likely Benign	0.492	Ambiguous	Likely Benign										0.186	Likely Benign	-0.60	Neutral	0.007	Benign	0.016	Benign	5.70	Benign	0.08	Tolerated			0.2762	0.1110		-1	-2	-5.3	-26.08
c.364C>A	P122T 2D AIThe SynGAP1 missense variant P122T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that P122T is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.672358	Binding	0.400	0.887	0.750											-3.954	Likely Benign	0.088	Likely Benign	Likely Benign										0.186	Likely Benign	-1.43	Neutral	0.580	Possibly Damaging	0.185	Benign	4.19	Benign	0.13	Tolerated			0.2068	0.5270		0	-1	0.9	3.99
c.4009T>C	F1337L 2D AIThe SynGAP1 missense variant F1337L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of evaluated predictors (six pathogenic vs. three benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625											-2.396	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.186	Likely Benign	-3.17	Deleterious	0.880	Possibly Damaging	0.899	Possibly Damaging	2.81	Benign	0.00	Affected	3.77	5	0.2765	0.3543		0	2	1.0	-34.02
c.4015A>G	N1339D 2D AIThe SynGAP1 missense variant N1339D is catalogued in gnomAD (ID 6‑33451889‑A‑G) but has no ClinVar submission. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. When aggregated into a consensus, the four contributing scores (AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) split evenly, leaving the SGM Consensus inconclusive. High‑accuracy assessments further indicate a benign outcome from AlphaMissense‑Optimized; the SGM Consensus and Foldetta predictions are unavailable. Overall, the majority of individual tools predict pathogenicity, and the high‑accuracy benign prediction does not overturn this trend. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.771762	Disordered	0.977585	Binding	0.396	0.687	1.000								6-33451889-A-G			-2.533	Likely Benign	0.634	Likely Pathogenic	Likely Benign										0.186	Likely Benign	-3.04	Deleterious	0.980	Probably Damaging	0.956	Probably Damaging	2.92	Benign	0.00	Affected	3.77	5	0.2087	0.4721		1	2	0.0	0.98
c.506A>G	D169G 2D AIThe SynGAP1 missense variant D169G is not 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a tie (2 pathogenic vs 2 benign) and is therefore unavailable; Foldetta results are not provided. Overall, the majority of standard predictors lean toward a benign classification, and this is consistent with the lack of ClinVar evidence. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.418646	Structured	0.497160	Uncertain	0.420	0.675	0.125											-9.853	Likely Pathogenic	0.820	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-2.44	Neutral	0.000	Benign	0.000	Benign	4.04	Benign	0.01	Affected			0.3907	0.6560		1	-1	3.1	-58.04
c.553T>A	S185T 2D AIThe SynGAP1 missense variant S185T 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. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a pathogenic impact. The variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-10.943	Likely Pathogenic	0.903	Likely Pathogenic	Ambiguous										0.186	Likely Benign	-2.54	Deleterious	0.596	Possibly Damaging	0.142	Benign	3.60	Benign	0.00	Affected			0.1484	0.6236		1	1	0.1	14.03
c.912C>A	D304E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304E missense variant has no ClinVar entry and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign effect, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-2.715	Likely Benign	0.233	Likely Benign	Likely Benign	0.34	Likely Benign	0.1	0.21	Likely Benign	0.28	Likely Benign	0.48	Likely Benign	0.186	Likely Benign	-3.29	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.77	Pathogenic	0.04	Affected			0.1504	0.6998		3	2	0.0	14.03
c.912C>G	D304E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D304E missense variant 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, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive. Overall, the balance of evidence favors a benign classification, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250											-2.715	Likely Benign	0.233	Likely Benign	Likely Benign	0.34	Likely Benign	0.1	0.21	Likely Benign	0.28	Likely Benign	0.48	Likely Benign	0.186	Likely Benign	-3.29	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.77	Pathogenic	0.04	Affected			0.1504	0.6998		3	2	0.0	14.03
c.991T>C	S331P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S331P is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are Rosetta, polyPhen‑2 HumDiv, and FATHMM. Two tools give inconclusive results: AlphaMissense‑Default and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.433034	Structured	0.346458	Uncertain	0.658	0.475	0.250											-5.104	Likely Benign	0.409	Ambiguous	Likely Benign	0.33	Likely Benign	0.2	2.35	Destabilizing	1.34	Ambiguous	0.44	Likely Benign	0.186	Likely Benign	-1.81	Neutral	0.784	Possibly Damaging	0.390	Benign	1.83	Pathogenic	0.26	Tolerated			0.2306	0.4086		1	-1	-0.8	10.04
c.1247T>A	L416Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict benign. Only two tools, polyPhen‑2 (HumDiv and HumVar), predict a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta remains uncertain. Overall, the evidence strongly supports a benign classification for this variant, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-6.445	Likely Benign	0.234	Likely Benign	Likely Benign	1.17	Ambiguous	0.1	0.54	Ambiguous	0.86	Ambiguous	0.88	Ambiguous	0.187	Likely Benign	-1.07	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.46	Tolerated			0.1281	0.0860		-2	-2	-7.3	14.97
c.1315C>A	L439M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L439M is reported in gnomAD (variant ID 6‑33438220‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on benign impact include REVEL, FoldX, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from premPS, polyPhen‑2 (HumDiv and HumVar) and SIFT. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta as inconclusive. Overall, the majority of evidence points to a benign effect; there is no ClinVar classification to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000								6-33438220-C-A	1	6.20e-7	-5.840	Likely Benign	0.363	Ambiguous	Likely Benign	-0.33	Likely Benign	0.1	1.34	Ambiguous	0.51	Ambiguous	1.01	Destabilizing	0.187	Likely Benign	-1.43	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	3.24	Benign	0.02	Affected	3.38	25	0.0720	0.2753		2	4	-1.9	18.03
c.1597G>C	A533P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict benign. Only FATHMM predicts pathogenic. Stability‑based methods are inconclusive: FoldX, Rosetta, and the combined Foldetta output are listed as uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as unavailable. Overall, the consensus of the majority of tools indicates a benign impact. This prediction does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000											-3.951	Likely Benign	0.081	Likely Benign	Likely Benign	-0.93	Ambiguous	0.3	-0.92	Ambiguous	-0.93	Ambiguous	-0.18	Likely Benign	0.187	Likely Benign	-0.48	Neutral	0.000	Benign	0.001	Benign	-1.26	Pathogenic	0.09	Tolerated			0.1925	0.5299		1	-1	-3.4	26.04
c.2155A>T	N719Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N719Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also uncertain. Overall, the majority of evaluated tools (7 benign vs 4 pathogenic) support a benign classification. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.384043	Structured	0.445381	Uncertain	0.961	0.386	0.000											-11.005	Likely Pathogenic	0.302	Likely Benign	Likely Benign	-0.38	Likely Benign	0.0	-0.62	Ambiguous	-0.50	Ambiguous	0.33	Likely Benign	0.187	Likely Benign	-4.15	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.09	Tolerated			0.0412	0.3951		-2	-2	2.2	49.07
c.2294G>T	S765I 2D AIThe SynGAP1 missense variant S765I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.370445	Structured	0.922652	Binding	0.335	0.865	0.250											-6.891	Likely Benign	0.699	Likely Pathogenic	Likely Benign										0.187	Likely Benign	-1.24	Neutral	0.996	Probably Damaging	0.985	Probably Damaging	4.09	Benign	0.69	Tolerated			0.0768	0.5577		-1	-2	5.3	26.08
c.2461T>G	C821G 2D AIThe SynGAP1 missense variant C821G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.613	Likely Benign	0.910	Likely Pathogenic	Ambiguous										0.187	Likely Benign	-2.94	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.68	Benign	0.05	Affected			0.3287	0.2747		-3	-3	-2.9	-46.09
c.2510T>G	V837G 2D AIThe SynGAP1 missense variant V837G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.626284	Binding	0.318	0.871	0.125											-2.599	Likely Benign	0.315	Likely Benign	Likely Benign										0.187	Likely Benign	0.93	Neutral	0.997	Probably Damaging	0.999	Probably Damaging	3.18	Benign	1.00	Tolerated			0.2260	0.2422		-1	-3	-4.6	-42.08
c.2614T>C	S872P 2D AIThe SynGAP1 missense variant S872P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also predicts Likely Benign. Foldetta results are not available for this variant. Overall, the majority of evidence indicates that S872P is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.662664	Binding	0.262	0.865	0.125											-4.291	Likely Benign	0.273	Likely Benign	Likely Benign										0.187	Likely Benign	-1.91	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.59	Benign	0.13	Tolerated			0.2321	0.5581		1	-1	-0.8	10.04
c.2741A>T	D914V 2D AIThe SynGAP1 missense variant D914V is listed in ClinVar (ID 2582846.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools 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, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as benign; Foldetta results are unavailable. Overall, the balance of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250					Uncertain		1				-4.260	Likely Benign	0.723	Likely Pathogenic	Likely Benign										0.187	Likely Benign	-2.24	Neutral	0.999	Probably Damaging	0.986	Probably Damaging	2.64	Benign	0.01	Affected	3.77	5	0.1316	0.7249		-3	-2	7.7	-15.96
c.2939A>T	H980L 2D AIThe SynGAP1 missense variant H980L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.974598	Binding	0.309	0.892	0.625											-1.984	Likely Benign	0.293	Likely Benign	Likely Benign										0.187	Likely Benign	-1.98	Neutral	0.625	Possibly Damaging	0.265	Benign	4.16	Benign	0.00	Affected			0.1488	0.5538		-2	-3	7.0	-23.98
c.3389A>G	K1130R 2D AIThe SynGAP1 missense variant K1130R is reported in gnomAD (variant ID 6‑33443941‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750								6-33443941-A-G			-2.163	Likely Benign	0.155	Likely Benign	Likely Benign										0.187	Likely Benign	-0.94	Neutral	0.014	Benign	0.008	Benign	5.44	Benign	0.00	Affected	4.32	4	0.5096	0.2074	Weaken	2	3	-0.6	28.01
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.3725A>C	E1242A 2D AIThe SynGAP1 missense variant E1242A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated tools (five pathogenic vs. three benign) predict a pathogenic impact. This prediction does not contradict 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.		Coiled-coil	0.557691	Disordered	0.456349	Uncertain	0.870	0.549	0.500											-5.654	Likely Benign	0.437	Ambiguous	Likely Benign										0.187	Likely Benign	-4.66	Deleterious	0.939	Possibly Damaging	0.735	Possibly Damaging	2.21	Pathogenic	0.00	Affected			0.2738	0.4169		0	-1	5.3	-58.04
c.380G>C	R127P 2D AIThe SynGAP1 missense variant R127P is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. In contrast, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default predict pathogenicity. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors a benign outcome. No Foldetta stability assessment is available, so it does not influence the interpretation. Overall, the preponderance of evidence points to a benign effect for R127P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.711716	Binding	0.333	0.870	0.625											-0.375	Likely Benign	0.703	Likely Pathogenic	Likely Benign										0.187	Likely Benign	-2.25	Neutral	0.748	Possibly Damaging	0.110	Benign	3.92	Benign	0.01	Affected			0.2295	0.3741		0	-2	2.9	-59.07
c.826C>G	P276A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P276A is reported in gnomAD (variant ID 6‑33437731‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. The high‑accuracy consensus methods give a benign signal: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is available). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.037156	Structured	0.338937	Uncertain	0.724	0.230	0.250								6-33437731-C-G	5	3.10e-6	-3.414	Likely Benign	0.058	Likely Benign	Likely Benign	1.42	Ambiguous	0.1	1.01	Ambiguous	1.22	Ambiguous	0.50	Likely Benign	0.187	Likely Benign	-2.31	Neutral	0.044	Benign	0.030	Benign	1.98	Pathogenic	0.57	Tolerated	3.38	19	0.3149	0.3669		-1	1	3.4	-26.04
c.1102C>A	P368T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P368T missense variant is not listed in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. FoldX, Rosetta, and Foldetta report uncertain or inconclusive stability changes and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie (2 benign, 2 pathogenic) and thus inconclusive, and Foldetta remains uncertain. Overall, the predictions are evenly split between benign and pathogenic, providing no definitive classification. The variant’s status does not contradict ClinVar, which has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.363090	Structured	0.439989	Uncertain	0.580	0.677	0.250											-5.308	Likely Benign	0.284	Likely Benign	Likely Benign	1.95	Ambiguous	0.6	1.61	Ambiguous	1.78	Ambiguous	0.45	Likely Benign	0.188	Likely Benign	-5.43	Deleterious	0.941	Possibly Damaging	0.527	Possibly Damaging	1.72	Pathogenic	0.01	Affected			0.1983	0.6155		0	-1	0.9	3.99
c.1612G>C	E538Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E538Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of evidence supports a benign impact. 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.		GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-10.380	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	0.07	Likely Benign	0.0	0.07	Likely Benign	0.07	Likely Benign	-0.08	Likely Benign	0.188	Likely Benign	-2.14	Neutral	0.890	Possibly Damaging	0.436	Benign	3.37	Benign	0.11	Tolerated			0.1127	0.3952		2	2	0.0	-0.98
c.211G>T	D71Y 2D AIThe SynGAP1 missense variant D71Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. Thus, 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		0.575842	Disordered	0.456046	Uncertain	0.350	0.799	0.375											-4.090	Likely Benign	0.740	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.49	Neutral	0.842	Possibly Damaging	0.189	Benign	4.00	Benign	0.00	Affected			0.0584	0.6086		-4	-3	2.2	48.09
c.2161A>C	I721L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I721L 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, PROVEAN, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Two tools (premPS and ESM1b) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the predictions are split, but the majority of high‑confidence tools lean toward a benign interpretation. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-7.843	In-Between	0.757	Likely Pathogenic	Likely Benign	0.35	Likely Benign	0.0	0.34	Likely Benign	0.35	Likely Benign	0.65	Ambiguous	0.188	Likely Benign	-1.83	Neutral	0.955	Possibly Damaging	0.985	Probably Damaging	2.37	Pathogenic	0.02	Affected			0.0627	0.3446		2	2	-0.7	0.00
c.2327G>A	G776D 2D AIThe SynGAP1 missense variant G776D is catalogued in gnomAD (ID 6‑33442485‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates benign. Foldetta stability analysis is unavailable, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G776D, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.377384	Structured	0.886983	Binding	0.296	0.888	0.250								6-33442485-G-A			0.388	Likely Benign	0.566	Likely Pathogenic	Likely Benign										0.188	Likely Benign	0.16	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.30	Benign	0.10	Tolerated	3.64	6	0.1835	0.2971		-1	1	-3.1	58.04
c.2422G>C	V808L 2D AIThe SynGAP1 missense variant V808L is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for V808L, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-4.723	Likely Benign	0.306	Likely Benign	Likely Benign										0.188	Likely Benign	-1.82	Neutral	0.911	Possibly Damaging	0.621	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1166	0.4745		2	1	-0.4	14.03
c.2422G>T	V808L 2D AIThe SynGAP1 missense variant V808L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.699094	Disordered	0.856438	Binding	0.289	0.903	0.500											-4.723	Likely Benign	0.306	Likely Benign	Likely Benign										0.188	Likely Benign	-1.82	Neutral	0.911	Possibly Damaging	0.621	Possibly Damaging	2.33	Pathogenic	0.00	Affected			0.1166	0.4745		2	1	-0.4	14.03
c.2525C>T	S842F 2D AIThe SynGAP1 missense variant S842F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL, polyPhen‑2 HumDiv and HumVar, whereas pathogenic calls come from PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default and AlphaMissense‑Optimized. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus result is consistent with this. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250											-14.590	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-4.12	Deleterious	0.029	Benign	0.043	Benign	1.98	Pathogenic	0.00	Affected			0.0584	0.5692		-3	-2	3.6	60.10
c.2651G>C	R884P 2D AIThe SynGAP1 missense variant R884P is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.641526	Binding	0.305	0.898	0.250											-1.882	Likely Benign	0.185	Likely Benign	Likely Benign										0.188	Likely Benign	-1.28	Neutral	0.000	Benign	0.002	Benign	2.58	Benign	0.20	Tolerated			0.2186	0.4337		0	-2	2.9	-59.07
c.2681G>T	G894V 2D AIThe SynGAP1 missense variant G894V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with the ClinVar status. 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.			0.788093	Disordered	0.425700	Uncertain	0.310	0.925	0.750											-5.047	Likely Benign	0.395	Ambiguous	Likely Benign										0.188	Likely Benign	-2.61	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.64	Benign	0.02	Affected			0.1187	0.4091		-1	-3	4.6	42.08
c.3221A>C	Q1074P 2D AIThe SynGAP1 missense variant Q1074P is listed in gnomAD (ID 6‑33443773‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single outlier. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.987006	Binding	0.339	0.897	0.750								6-33443773-A-C	1	6.23e-7	-4.259	Likely Benign	0.083	Likely Benign	Likely Benign										0.188	Likely Benign	0.52	Neutral	0.925	Possibly Damaging	0.432	Benign	2.66	Benign	0.13	Tolerated	3.77	5	0.2046	0.5784		-1	0	1.9	-31.01
c.3439A>G	T1147A 2D AIThe SynGAP1 missense variant T1147A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.746520	Binding	0.345	0.839	0.875											-3.115	Likely Benign	0.061	Likely Benign	Likely Benign										0.188	Likely Benign	-1.60	Neutral	0.001	Benign	0.004	Benign	5.54	Benign	0.03	Affected			0.3816	0.3705		1	0	2.5	-30.03
c.3475T>C	S1159P 2D AIThe SynGAP1 missense variant S1159P 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, which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. 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 (majority vote) is benign. No Foldetta stability prediction is available for this residue. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.867068	Binding	0.343	0.846	0.375											-3.656	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-2.06	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.64	Benign	0.14	Tolerated			0.1807	0.5111		1	-1	-0.8	10.04
c.3480C>A	N1160K 2D AIThe SynGAP1 missense variant N1160K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.768	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-3.92	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.04	Affected			0.1919	0.5017		1	0	-0.4	14.07
c.3604A>T	I1202F 2D AIThe SynGAP1 missense variant I1202F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is likely pathogenic. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.510422	Binding	0.874	0.593	0.250											-12.304	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.188	Likely Benign	-3.23	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.81	Pathogenic	0.02	Affected			0.0583	0.2079		1	0	-1.7	34.02
c.3816G>T	E1272D 2D AIThe SynGAP1 missense variant E1272D is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33447864‑G‑T). Functional prediction tools show mixed results: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized tool classifies the change as benign, while the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. No Foldetta stability assessment is available for this variant. Overall, the majority of conventional predictors and the consensus score lean toward pathogenicity, which is consistent with the SGM‑Consensus designation but contradicts the benign calls from AlphaMissense‑Optimized and a few other tools. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion aligns with the SGM‑Consensus prediction rather than the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500								6-33447864-G-T			-4.781	Likely Benign	0.751	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.1450	0.3471		2	3	0.0	-14.03
c.383C>G	P128R 2D AIThe SynGAP1 missense variant P128R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. When predictions are grouped by consensus, the majority of methods (six) predict benign, while three predict pathogenic. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a likely benign effect. Foldetta results are unavailable. Overall, the computational evidence favors a benign classification for P128R, and this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.713069	Binding	0.376	0.878	0.625											-5.048	Likely Benign	0.748	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-1.76	Neutral	0.984	Probably Damaging	0.601	Possibly Damaging	4.19	Benign	0.08	Tolerated			0.1810	0.2401		0	-2	-2.9	59.07
c.3917A>T	N1306I 2D AIThe SynGAP1 missense variant N1306I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.902190	Binding	0.367	0.888	0.875											-3.234	Likely Benign	0.296	Likely Benign	Likely Benign										0.188	Likely Benign	-6.15	Deleterious	0.890	Possibly Damaging	0.761	Possibly Damaging	2.56	Benign	0.00	Affected			0.0837	0.6672		-2	-3	8.0	-0.94
c.524A>T	Q175L 2D AIThe SynGAP1 missense variant Q175L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, seven tools favor benign while two favor pathogenic, with no ClinVar evidence to contradict this. Thus, the variant is most likely benign based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-8.699	Likely Pathogenic	0.579	Likely Pathogenic	Likely Benign										0.188	Likely Benign	-2.46	Neutral	0.118	Benign	0.039	Benign	4.10	Benign	0.14	Tolerated			0.0647	0.5109		-2	-2	7.3	-14.97
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.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.996C>G	D332E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D332E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign classification. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-4.915	Likely Benign	0.320	Likely Benign	Likely Benign	0.50	Ambiguous	0.2	0.04	Likely Benign	0.27	Likely Benign	0.35	Likely Benign	0.188	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.29	Pathogenic	0.24	Tolerated			0.0970	0.3915		3	2	0.0	14.03
c.2312C>T	S771F 2D AIThe SynGAP1 missense variant S771F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.436924	Structured	0.922503	Binding	0.306	0.883	0.250											-7.988	In-Between	0.525	Ambiguous	Likely Benign										0.189	Likely Benign	-2.29	Neutral	0.990	Probably Damaging	0.892	Possibly Damaging	4.02	Benign	0.04	Affected			0.0624	0.5428		-3	-2	3.6	60.10
c.2350G>C	A784P 2D AIThe SynGAP1 missense variant A784P is reported in gnomAD (variant ID 6-33442902‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact for A784P. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625								6-33442902-G-C	4	2.48e-6	-3.777	Likely Benign	0.154	Likely Benign	Likely Benign										0.189	Likely Benign	-0.73	Neutral	0.586	Possibly Damaging	0.396	Benign	2.66	Benign	0.19	Tolerated	3.64	6	0.1846	0.4771		-1	1	-3.4	26.04
c.2572A>C	S858R 2D AIThe SynGAP1 missense variant S858R is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields 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 conclusion does not contradict the ClinVar status, which currently has no pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-3.924	Likely Benign	0.753	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-1.18	Neutral	0.818	Possibly Damaging	0.899	Possibly Damaging	4.12	Benign	0.02	Affected			0.0996	0.3778		0	-1	-3.7	69.11
c.2843G>C	G948A 2D AIThe SynGAP1 missense variant G948A is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988505	Disordered	0.862121	Binding	0.365	0.919	0.750											-5.627	Likely Benign	0.078	Likely Benign	Likely Benign										0.189	Likely Benign	0.04	Neutral	0.288	Benign	0.103	Benign	4.64	Benign	0.39	Tolerated			0.3350	0.4957		1	0	2.2	14.03
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.3088C>G	H1030D 2D AIThe SynGAP1 missense variant H1030D is reported in gnomAD (variant ID 6‑33443640‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only SIFT predicts a pathogenic effect, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.849326	Disordered	0.995856	Binding	0.375	0.735	0.500								6-33443640-C-G	1	6.19e-7	-3.500	Likely Benign	0.424	Ambiguous	Likely Benign										0.189	Likely Benign	-0.85	Neutral	0.126	Benign	0.066	Benign	2.78	Benign	0.05	Affected	3.77	5	0.2273	0.2422		-1	1	-0.3	-22.05
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.3364G>A	G1122S 2D AIThe SynGAP1 missense variant G1122S is listed in ClinVar as a benign alteration (ClinVar ID 643187.0) and is present in gnomAD (gnomAD ID 6‑33443916‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely benign, while Foldetta’s protein‑folding stability result is unavailable. Overall, the variant is most likely benign, and this assessment is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.814918	Binding	0.357	0.932	0.875					Benign/Likely benign		2	6-33443916-G-A	27	1.79e-5	-4.880	Likely Benign	0.072	Likely Benign	Likely Benign										0.189	Likely Benign	-0.08	Neutral	0.022	Benign	0.006	Benign	4.89	Benign	0.92	Tolerated	3.77	5	0.2537	0.5111		1	0	-0.4	30.03
c.3480C>G	N1160K 2D AIThe SynGAP1 missense variant N1160K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.585406	Disordered	0.861611	Binding	0.361	0.836	0.375											-3.768	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic										0.189	Likely Benign	-3.92	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.83	Pathogenic	0.04	Affected			0.1919	0.5017		1	0	-0.4	14.07
c.3695A>C	K1232T 2D AIThe SynGAP1 missense variant K1232T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-9.276	Likely Pathogenic	0.568	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-4.49	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.1846	0.3196		0	-1	3.2	-27.07
c.3816G>C	E1272D 2D AIThe SynGAP1 missense variant E1272D has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments further show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect. There is no ClinVar classification to contradict this conclusion, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500											-4.781	Likely Benign	0.751	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.53	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.1450	0.3471		2	3	0.0	-14.03
c.76G>A	G26R 2D AIThe SynGAP1 missense variant G26R is listed in ClinVar as a benign alteration (ClinVar ID 1521495.0) and is present in the gnomAD database (gnomAD ID 6‑33423485‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence supports a benign impact, aligning with the ClinVar designation and indicating no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375					Benign		1	6-33423485-G-A	3	1.86e-6	-2.946	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.22	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.87	Benign	0.00	Affected	4.32	1	0.1097	0.4407		-3	-2	-4.1	99.14
c.76G>C	G26R 2D AIThe SynGAP1 missense variant G26R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of the four high‑accuracy tools) also yields benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy consensus—indicates that G26R is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375											-2.946	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.189	Likely Benign	-2.22	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.87	Benign	0.00	Affected	4.32	1	0.1097	0.4407		-3	-2	-4.1	99.14
c.892C>T	P298S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P298S is listed in ClinVar as Benign (ClinVar ID 2965590.0) and is present in gnomAD (ID 6‑33437797‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. No evidence from FoldX, Rosetta, or premPS is available to support either outcome. Overall, the majority of predictions support a benign impact, aligning with the ClinVar designation. Thus, the variant is most likely benign and does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500					Benign		1	6-33437797-C-T	5	3.10e-6	-6.342	Likely Benign	0.144	Likely Benign	Likely Benign	1.38	Ambiguous	0.2	1.41	Ambiguous	1.40	Ambiguous	0.58	Ambiguous	0.189	Likely Benign	-1.20	Neutral	0.991	Probably Damaging	0.898	Possibly Damaging	2.03	Pathogenic	0.85	Tolerated	3.39	20	0.3678	0.5855		-1	1	0.8	-10.04
c.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.2018T>A	L673Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX and Foldetta, as well as AlphaMissense‑Default, are inconclusive and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta remains uncertain. Overall, the majority of available predictions (seven pathogenic vs. three benign) indicate 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.		GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-11.963	Likely Pathogenic	0.445	Ambiguous	Likely Benign	1.56	Ambiguous	0.2	2.32	Destabilizing	1.94	Ambiguous	1.02	Destabilizing	0.190	Likely Benign	-3.40	Deleterious	1.000	Probably Damaging	0.968	Probably Damaging	3.32	Benign	0.03	Affected			0.1045	0.1172		-2	-2	-7.3	14.97
c.2206C>T	R736C 2D AISynGAP1 missense variant R736C is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441671‑C‑T). Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also returns benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates a benign effect, which does not conflict with the ClinVar uncertain designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.926919	Disordered	0.415259	Uncertain	0.305	0.771	0.875					Conflicting		3	6-33441671-C-T	8	4.96e-6	-7.113	In-Between	0.120	Likely Benign	Likely Benign										0.190	Likely Benign	-2.06	Neutral	0.999	Probably Damaging	0.825	Possibly Damaging	2.48	Pathogenic	0.00	Affected	4.07	3	0.3740	0.1691		-4	-3	7.0	-53.05
c.2353C>G	R785G 2D AIThe SynGAP1 missense variant R785G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome. High‑accuracy assessments further reveal that AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus again suggests pathogenicity; Foldetta stability analysis is not available for this variant. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the SGM‑Consensus result. Because the variant is not present in ClinVar, there is no existing clinical classification to contradict; thus, based on the available computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625											-3.684	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-3.44	Deleterious	0.980	Probably Damaging	0.818	Possibly Damaging	2.25	Pathogenic	0.00	Affected			0.3695	0.3686		-3	-2	4.1	-99.14
c.2369C>T	T790I 2D AIThe SynGAP1 missense variant T790I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.964893	Disordered	0.509280	Binding	0.385	0.896	0.875											-3.556	Likely Benign	0.482	Ambiguous	Likely Benign										0.190	Likely Benign	-3.08	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.28	Pathogenic	0.01	Affected			0.0987	0.5431		0	-1	5.2	12.05
c.2461T>A	C821S 2D AIThe SynGAP1 missense variant C821S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for C821S, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-0.425	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-0.47	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.91	Benign	1.00	Tolerated			0.5284	0.2012	Weaken	0	-1	-3.3	-16.06
c.2926T>G	F976V 2D AIThe SynGAP1 missense variant F976V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625											-3.328	Likely Benign	0.268	Likely Benign	Likely Benign										0.190	Likely Benign	-1.32	Neutral	0.451	Benign	0.157	Benign	4.18	Benign	0.23	Tolerated			0.2696	0.2902		-1	-1	1.4	-48.04
c.2948G>T	S983I 2D AIThe SynGAP1 missense variant S983I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that S983I is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-6.259	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.67	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1380	0.4625		-1	-2	5.3	26.08
c.2949C>A	S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that S983R is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently lacks a classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-4.733	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1163	0.3740		0	-1	-3.7	69.11
c.2949C>G	S983R 2D AIThe SynGAP1 missense variant S983R is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S983R is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently lacks a pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-4.733	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1163	0.3740		0	-1	-3.7	69.11
c.334G>T	G112W 2D AIThe SynGAP1 missense variant G112W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic interpretation. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750											-6.382	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-3.98	Deleterious	0.983	Probably Damaging	0.778	Possibly Damaging	3.90	Benign	0.00	Affected			0.0631	0.4212		-7	-2	-0.5	129.16
c.3394T>A	S1132T 2D AIThe SynGAP1 missense variant S1132T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification—there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.845506	Binding	0.289	0.894	0.750											-3.700	Likely Benign	0.073	Likely Benign	Likely Benign										0.190	Likely Benign	-0.71	Neutral	0.011	Benign	0.017	Benign	5.45	Benign	0.50	Tolerated			0.1552	0.6309		1	1	0.1	14.03
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.3857A>C	E1286A 2D AIThe SynGAP1 missense variant E1286A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.817022	Binding	0.544	0.765	0.750											-3.136	Likely Benign	0.153	Likely Benign	Likely Benign										0.190	Likely Benign	-2.37	Neutral	0.770	Possibly Damaging	0.303	Benign	2.46	Pathogenic	0.02	Affected			0.3820	0.5016		0	-1	5.3	-58.04
c.4018A>C	T1340P 2D AIThe SynGAP1 missense variant T1340P is catalogued in gnomAD (ID 6‑33451892‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while only SIFT predicts a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that T1340P is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.977899	Binding	0.444	0.697	0.750								6-33451892-A-C			-2.681	Likely Benign	0.102	Likely Benign	Likely Benign										0.190	Likely Benign	-1.81	Neutral	0.334	Benign	0.099	Benign	4.08	Benign	0.01	Affected	3.77	5	0.2268	0.4983		-1	0	-0.9	-3.99
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.445A>C	K149Q 2D AIThe SynGAP1 missense variant K149Q is not 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. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) 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 no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-11.430	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.99	Neutral	0.535	Possibly Damaging	0.310	Benign	3.61	Benign	0.00	Affected			0.5243	0.1454	Weaken	1	1	0.4	-0.04
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.484C>G	R162G 2D AIThe SynGAP1 missense variant R162G is listed in ClinVar (ID 2703066.0) with an uncertain significance status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of predictions support a benign impact, and this is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250					Uncertain		1				-6.985	Likely Benign	0.664	Likely Pathogenic	Likely Benign										0.190	Likely Benign	-0.73	Neutral	0.487	Possibly Damaging	0.272	Benign	4.09	Benign	0.78	Tolerated	3.74	4	0.3562	0.4308		-2	-3	4.1	-99.14
c.489C>A	F163L 2D AIThe SynGAP1 missense variant F163L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this assessment does not contradict the ClinVar status, which currently has no classification for F163L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-6.380	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.22	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.21	Benign	0.37	Tolerated			0.2191	0.3491		2	0	1.0	-34.02
c.489C>G	F163L 2D AIThe SynGAP1 missense variant F163L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, six tools favor a benign outcome versus four favoring pathogenicity, and the high‑accuracy predictions are conflicting. Thus, the variant is most likely benign based on the current consensus, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-6.380	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-1.22	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.21	Benign	0.37	Tolerated			0.2191	0.3491		2	0	1.0	-34.02
c.490C>G	R164G 2D AIThe SynGAP1 missense variant R164G has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split opinion: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: the SGM‑Consensus remains Likely Pathogenic, AlphaMissense‑Optimized is inconclusive, and the Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic impact. Because there is no ClinVar classification to oppose 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		0.414856	Structured	0.512396	Binding	0.317	0.666	0.250											-12.416	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous										0.190	Likely Benign	-3.01	Deleterious	0.487	Possibly Damaging	0.272	Benign	3.77	Benign	0.00	Affected			0.3657	0.3631		-3	-2	4.1	-99.14
c.536A>T	E179V 2D AIThe SynGAP1 missense variant E179V 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 is not contradicted by any ClinVar annotation. 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											-10.930	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic										0.190	Likely Benign	-4.34	Deleterious	0.596	Possibly Damaging	0.328	Benign	3.94	Benign	0.01	Affected			0.1077	0.7864		-2	-2	7.7	-29.98
c.66A>C	R22S 2D AIThe SynGAP1 missense variant R22S is 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 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; a Foldetta stability prediction is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.441505	Uncertain	0.377	0.891	0.500											-3.419	Likely Benign	0.602	Likely Pathogenic	Likely Benign										0.190	Likely Benign	0.01	Neutral	0.462	Possibly Damaging	0.227	Benign	4.28	Benign	0.00	Affected	4.32	1	0.3252	0.5187		-1	0	3.7	-69.11
c.66A>T	R22S 2D AIThe SynGAP1 missense variant R22S is listed in gnomAD (ID 6‑33420330‑A‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its stability impact is unavailable. Overall, the majority of evidence points to a benign effect, and this is not in conflict with ClinVar, which has no classification for R22S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.441505	Uncertain	0.377	0.891	0.500								6-33420330-A-T			-3.419	Likely Benign	0.602	Likely Pathogenic	Likely Benign										0.190	Likely Benign	0.01	Neutral	0.462	Possibly Damaging	0.227	Benign	4.28	Benign	0.00	Affected	4.32	1	0.3252	0.5187		-1	0	3.7	-69.11
c.1042G>A	V348M 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V348M is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that report a clear outcome fall into two groups: benign calls come from REVEL, Foldetta, PROVEAN, and AlphaMissense‑Optimized; pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools (FoldX, Rosetta, premPS, AlphaMissense‑Default, ESM1b) give uncertain results, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is unavailable due to no majority. High‑accuracy methods specifically show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus is not available. With four benign and four pathogenic predictions, the evidence is evenly split, providing no definitive direction. Therefore, the variant is not clearly benign or pathogenic based on current predictions, and this lack of consensus does not contradict its ClinVar uncertain status. 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					Uncertain		1				-7.076	In-Between	0.546	Ambiguous	Likely Benign	-1.19	Ambiguous	0.1	0.72	Ambiguous	-0.24	Likely Benign	0.76	Ambiguous	0.191	Likely Benign	-1.62	Neutral	0.966	Probably Damaging	0.564	Possibly Damaging	1.58	Pathogenic	0.03	Affected	3.37	25	0.0903	0.4748		2	1	-2.3	32.06	253.8	-47.4	-0.3	0.1	0.2	0.1						X		Potentially Benign	The iso-propyl side chain of Val348, located in an anti-parallel β sheet strand (res. Gly341-Pro349), packs against multiple hydrophobic C2 domain residues (e.g., Leu353, Leu323, Leu402). In the variant simulations, the thioether side chain of Met348 can form similar interactions as valine due to its comparable hydrophobic profile. In fact, the thioether group of methionine can even stack favorably with the phenol ring of Tyr363 in the anti-parallel β sheet strand (res. Ala399-Ile411). Overall, the residue swap does not appear to cause negative effects on the protein structure based on the simulations.
c.1436G>A	R479Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R479Q is listed in ClinVar with an “Uncertain” significance and is present in gnomAD (variant ID 6‑33438468‑G‑A). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv and HumVar both predict a pathogenic impact. Uncertain or inconclusive results come from FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also as likely benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect, and this consensus does not contradict the ClinVar “Uncertain” status; 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	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000					Uncertain		1	6-33438468-G-A	7	4.34e-6	-7.109	In-Between	0.259	Likely Benign	Likely Benign	0.54	Ambiguous	0.1	0.57	Ambiguous	0.56	Ambiguous	0.49	Likely Benign	0.191	Likely Benign	-1.16	Neutral	1.000	Probably Damaging	0.991	Probably Damaging	3.42	Benign	0.31	Tolerated	3.39	32	0.2448	0.1812		1	1	1.0	-28.06
c.2282G>A	R761Q 2D AIThe SynGAP1 missense variant R761Q is listed in ClinVar (ID 2882770.0) with an “Uncertain” status and is present in gnomAD (6‑33441747‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250					Uncertain		1	6-33441747-G-A	11	6.81e-6	-4.187	Likely Benign	0.202	Likely Benign	Likely Benign										0.191	Likely Benign	-0.63	Neutral	0.996	Probably Damaging	0.878	Possibly Damaging	2.75	Benign	0.40	Tolerated	3.99	5	0.2640	0.2329		1	1	1.0	-28.06
c.2525C>A	S842Y 2D AIThe SynGAP1 missense variant S842Y is listed in ClinVar as Pathogenic (ClinVar ID 624244.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, in agreement with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.617281	Binding	0.274	0.861	0.250					Likely Pathogenic		1				-16.124	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-4.28	Deleterious	0.944	Possibly Damaging	0.676	Possibly Damaging	1.97	Pathogenic	0.00	Affected	3.77	5	0.0576	0.5403		-3	-2	-0.5	76.10
c.2669G>C	R890P 2D AIThe SynGAP1 missense variant R890P is listed in ClinVar (ID 575680.0) as Benign and is present in gnomAD (6‑33443221‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar status, showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625					Likely Benign		2	6-33443221-G-C	28	1.74e-5	-1.931	Likely Benign	0.301	Likely Benign	Likely Benign										0.191	Likely Benign	-1.21	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.02	Benign	0.28	Tolerated	4.32	4	0.2239	0.3551		0	-2	2.9	-59.07
c.2837G>C	G946A 2D AIThe SynGAP1 missense variant G946A is not reported 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G946A, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985417	Disordered	0.845792	Binding	0.357	0.920	0.750											-7.004	In-Between	0.079	Likely Benign	Likely Benign										0.191	Likely Benign	0.33	Neutral	0.649	Possibly Damaging	0.209	Benign	4.77	Benign	0.00	Affected			0.3378	0.4957		1	0	2.2	14.03
c.320G>C	R107T 2D AIThe SynGAP1 missense variant R107T is not 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 classifying the variant as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign) and Foldetta results are unavailable. Overall, the majority of predictions (five benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.663448	Binding	0.331	0.863	0.875											-2.902	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-2.63	Deleterious	0.421	Benign	0.050	Benign	2.98	Benign	0.00	Affected			0.1549	0.4761		-1	-1	3.8	-55.08
c.3272T>G	L1091R 2D AIThe SynGAP1 missense variant L1091R is not 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 predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools (five pathogenic vs. three benign) suggest a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000											-3.662	Likely Benign	0.896	Likely Pathogenic	Ambiguous										0.191	Likely Benign	-1.51	Neutral	0.997	Probably Damaging	0.939	Probably Damaging	2.47	Pathogenic	0.02	Affected			0.1274	0.1357		-3	-2	-8.3	43.03
c.3851T>C	L1284P 2D AIThe SynGAP1 missense variant L1284P is not reported in ClinVar (no ClinVar ID) but is present in gnomAD (ID 6‑33447899‑T‑C). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. Foldetta results are unavailable. Overall, the balance of evidence slightly favors a pathogenic interpretation (five pathogenic versus four benign predictions). This assessment does not conflict with ClinVar, as the variant has no ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875								6-33447899-T-C			-2.451	Likely Benign	0.076	Likely Benign	Likely Benign										0.191	Likely Benign	-3.05	Deleterious	0.990	Probably Damaging	0.722	Possibly Damaging	2.48	Pathogenic	0.01	Affected	3.77	5	0.3307	0.0848		-3	-3	-5.4	-16.04
c.4007A>C	E1336A 2D AIThe SynGAP1 missense variant E1336A is not 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, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of evidence (five benign vs. three pathogenic) supports a benign classification. This prediction does not contradict any ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750											-3.545	Likely Benign	0.879	Likely Pathogenic	Ambiguous										0.191	Likely Benign	-3.78	Deleterious	0.345	Benign	0.099	Benign	3.22	Benign	0.00	Affected			0.4000	0.7385		0	-1	5.3	-58.04
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.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.47T>G	M16R 2D AIThe SynGAP1 missense variant M16R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic call comes from SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus also indicates likely benign, and no Foldetta stability data are available. Taken together, the preponderance of evidence supports a benign classification for M16R, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.440853	Structured	0.459925	Uncertain	0.346	0.908	0.375											-1.475	Likely Benign	0.485	Ambiguous	Likely Benign										0.191	Likely Benign	-0.25	Neutral	0.014	Benign	0.003	Benign	4.21	Benign	0.00	Affected			0.1992	0.1093		0	-1	-6.4	24.99
c.484C>A	R162S 2D AIThe SynGAP1 missense variant R162S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). AlphaMissense‑Optimized is currently Uncertain, and no Foldetta stability result is available. Overall, the majority of high‑accuracy and consensus predictions indicate a benign impact. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250											-1.395	Likely Benign	0.894	Likely Pathogenic	Ambiguous										0.191	Likely Benign	-0.24	Neutral	0.487	Possibly Damaging	0.272	Benign	4.14	Benign	0.75	Tolerated			0.3080	0.4974		0	-1	3.7	-69.11
c.497C>T	A166V 2D AIThe SynGAP1 missense variant A166V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.505037	Binding	0.384	0.658	0.125											-6.689	Likely Benign	0.274	Likely Benign	Likely Benign										0.191	Likely Benign	-1.09	Neutral	0.141	Benign	0.091	Benign	4.07	Benign	0.02	Affected			0.1027	0.4281		0	0	2.4	28.05
c.573T>A	S191R 2D AIThe SynGAP1 missense variant S191R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.573T>G	S191R 2D AIThe SynGAP1 missense variant S191R 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 is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-10.046	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.191	Likely Benign	-3.82	Deleterious	0.838	Possibly Damaging	0.367	Benign	3.78	Benign	0.01	Affected			0.0973	0.4344		0	-1	-3.7	69.11
c.892C>G	P298A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P298A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from FoldX or Rosetta alone is conclusive. Based on the preponderance of benign predictions and the lack of pathogenic consensus, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500											-6.082	Likely Benign	0.074	Likely Benign	Likely Benign	1.22	Ambiguous	0.1	1.17	Ambiguous	1.20	Ambiguous	0.50	Likely Benign	0.191	Likely Benign	-0.98	Neutral	0.885	Possibly Damaging	0.589	Possibly Damaging	1.94	Pathogenic	0.66	Tolerated			0.3761	0.5787		1	-1	3.4	-26.04
c.996C>A	D332E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D332E 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, Rosetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Overall, the majority of evidence points to a benign effect. 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.		C2	0.339168	Structured	0.336528	Uncertain	0.537	0.445	0.375											-4.915	Likely Benign	0.320	Likely Benign	Likely Benign	0.50	Ambiguous	0.2	0.04	Likely Benign	0.27	Likely Benign	0.35	Likely Benign	0.191	Likely Benign	-2.66	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.29	Pathogenic	0.24	Tolerated			0.0970	0.3915		3	2	0.0	14.03
c.1300G>A	V434I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434I (ClinVar ID 212346.0, status Uncertain) is present in gnomAD (ID 6‑33438205‑G‑A). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No predictions or stability results are missing or inconclusive. Based on the collective evidence, the variant is most likely benign, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000					Uncertain		1	6-33438205-G-A	1	6.19e-7	-6.999	Likely Benign	0.129	Likely Benign	Likely Benign	-0.04	Likely Benign	0.0	0.22	Likely Benign	0.09	Likely Benign	0.31	Likely Benign	0.192	Likely Benign	-0.82	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.53	Benign	0.18	Tolerated	3.37	29	0.0675	0.3415		4	3	0.3	14.03	246.7	-27.7	0.0	0.0	0.1	0.0						X		Potentially Benign	The iso-propyl side chain of Val434, located at the end of an α helix (res. Met414-Glu436), packs against hydrophobic residues in an interhelix space (e.g., Met430, Ala707, Leu711). In the variant simulations, the sec-butyl group of Ile434 is able to form the same hydrophobic interactions. Accordingly, the residue swap does not negatively affect the protein structure based on the simulations.
c.1909T>C	S637P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S637P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls arise from FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments give a pathogenic signal: the SGM Consensus predicts likely pathogenic, Foldetta predicts destabilizing pathogenic effects, whereas AlphaMissense‑Optimized remains uncertain. Overall, 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	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-11.455	Likely Pathogenic	0.793	Likely Pathogenic	Ambiguous	6.73	Destabilizing	0.1	6.36	Destabilizing	6.55	Destabilizing	0.44	Likely Benign	0.192	Likely Benign	-3.12	Deleterious	0.946	Possibly Damaging	0.360	Benign	3.36	Benign	0.03	Affected			0.2374	0.4094		1	-1	-0.8	10.04
c.2297C>G	S766C 2D AIThe SynGAP1 missense variant S766C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S766C, 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		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250											-7.681	In-Between	0.326	Likely Benign	Likely Benign										0.192	Likely Benign	-2.02	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	4.07	Benign	0.00	Affected			0.1049	0.6110		0	-1	3.3	16.06
c.2416T>G	F806V 2D AIThe SynGAP1 missense variant F806V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic; a Foldetta stability analysis is unavailable. Overall, the balance of evidence from the majority of prediction algorithms points to a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.736850	Disordered	0.847454	Binding	0.276	0.904	0.500											-4.548	Likely Benign	0.676	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-3.79	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.16	Pathogenic	0.02	Affected			0.2464	0.1325		-1	-1	1.4	-48.04
c.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.2714G>A	R905H 2D AIThe SynGAP1 missense variant R905H is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443266‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta’s protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.618085	Binding	0.291	0.920	0.250					Uncertain		1	6-33443266-G-A	8	4.96e-6	-4.182	Likely Benign	0.457	Ambiguous	Likely Benign										0.192	Likely Benign	-1.11	Neutral	1.000	Probably Damaging	0.991	Probably Damaging	2.59	Benign	0.09	Tolerated	3.77	5	0.2658	0.2279		2	0	1.3	-19.05
c.2852A>T	H951L 2D AIThe SynGAP1 missense variant H951L is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population evidence. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.901477	Binding	0.415	0.925	0.750											-4.822	Likely Benign	0.087	Likely Benign	Likely Benign										0.192	Likely Benign	-0.99	Neutral	0.022	Benign	0.018	Benign	5.47	Benign	0.43	Tolerated			0.2224	0.4526		-2	-3	7.0	-23.98
c.3460A>T	T1154S 2D AIThe SynGAP1 missense variant T1154S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also reports it as likely pathogenic. Foldetta results are unavailable. Overall, the consensus of the available predictions indicates that T1154S is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.838654	Binding	0.382	0.851	0.625											-3.253	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-2.92	Deleterious	0.997	Probably Damaging	0.989	Probably Damaging	1.78	Pathogenic	0.00	Affected			0.2817	0.3206		1	1	-0.1	-14.03
c.3622C>T	R1208W 2D AIThe SynGAP1 missense variant R1208W is recorded in gnomAD (variant ID 6‑33446614‑C‑T) but has no ClinVar entry. Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic.” No Foldetta stability result is available. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R1208W is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375								6-33446614-C-T	1	6.20e-7	-12.124	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.192	Likely Benign	-5.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.47	Pathogenic	0.00	Affected	3.77	5	0.1247	0.2962		-3	2	3.6	30.03
c.3811G>A	E1271K 2D AIThe SynGAP1 missense variant E1271K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, whereas Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the preponderance of evidence—both from general predictors and the SGM Consensus—leans toward pathogenicity. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.767529	Binding	0.832	0.666	0.375											-2.295	Likely Benign	0.689	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-3.24	Deleterious	0.905	Possibly Damaging	0.433	Benign	2.07	Pathogenic	0.00	Affected			0.1780	0.5888		0	1	-0.4	-0.94
c.3920C>A	P1307Q 2D AIThe SynGAP1 missense variant P1307Q is listed in ClinVar (ID 982827.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451794‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.798249	Disordered	0.913511	Binding	0.491	0.901	0.875					Uncertain		1	6-33451794-C-A			-4.227	Likely Benign	0.114	Likely Benign	Likely Benign										0.192	Likely Benign	-0.88	Neutral	0.988	Probably Damaging	0.765	Possibly Damaging	2.82	Benign	0.03	Affected	3.77	5	0.1629	0.4464		0	-1	-1.9	31.01
c.473A>C	Q158P 2D AIThe SynGAP1 missense variant Q158P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q158P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.527565	Binding	0.286	0.750	0.375											-6.120	Likely Benign	0.150	Likely Benign	Likely Benign										0.192	Likely Benign	-0.99	Neutral	0.851	Possibly Damaging	0.374	Benign	4.12	Benign	0.03	Affected			0.2167	0.4190		0	-1	1.9	-31.01
c.520A>C	M174L 2D AIThe SynGAP1 missense variant M174L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact for M174L. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-5.839	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-0.82	Neutral	0.055	Benign	0.011	Benign	4.21	Benign	0.46	Tolerated			0.1335	0.4545		4	2	1.9	-18.03
c.520A>T	M174L 2D AIThe SynGAP1 missense variant M174L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact for M174L. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375											-5.839	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.192	Likely Benign	-0.82	Neutral	0.055	Benign	0.011	Benign	4.21	Benign	0.46	Tolerated			0.1335	0.4545		4	2	1.9	-18.03
c.985C>A	R329S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R329S 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 HumVar, and FATHMM. Those 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, Foldetta, premPS) 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. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	1.80	Ambiguous	0.3	0.78	Ambiguous	1.29	Ambiguous	0.78	Ambiguous	0.192	Likely Benign	-3.36	Deleterious	0.653	Possibly Damaging	0.226	Benign	4.07	Benign	0.04	Affected			0.2886	0.3625		0	-1	3.7	-69.11
c.1597G>T	A533S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only FATHMM predicts a pathogenic outcome. When predictions are grouped by consensus, the benign group contains all tools except FATHMM, which stands alone in the pathogenic group. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates a benign effect. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000											-3.740	Likely Benign	0.075	Likely Benign	Likely Benign	0.24	Likely Benign	0.0	-0.05	Likely Benign	0.10	Likely Benign	-0.14	Likely Benign	0.193	Likely Benign	0.33	Neutral	0.009	Benign	0.039	Benign	-1.14	Pathogenic	0.45	Tolerated			0.2612	0.5334		1	1	-2.6	16.00
c.1919C>T	T640I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T640I is not 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, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Only PROVEAN predicts a pathogenic outcome. The remaining tools (FoldX, Rosetta, ESM1b, AlphaMissense‑Default, and Foldetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is unavailable due to a tie, and Foldetta also yields an uncertain stability change. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.066181	Structured	0.137043	Uncertain	0.893	0.284	0.000											-7.256	In-Between	0.358	Ambiguous	Likely Benign	0.70	Ambiguous	0.1	0.66	Ambiguous	0.68	Ambiguous	0.28	Likely Benign	0.193	Likely Benign	-2.75	Deleterious	0.322	Benign	0.022	Benign	3.46	Benign	0.12	Tolerated			0.1030	0.4793		0	-1	5.2	12.05
c.2009T>G	L670R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign effect. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.801	Likely Pathogenic	0.552	Ambiguous	Likely Benign	0.64	Ambiguous	0.1	1.42	Ambiguous	1.03	Ambiguous	0.67	Ambiguous	0.193	Likely Benign	-1.74	Neutral	0.993	Probably Damaging	0.755	Possibly Damaging	3.43	Benign	0.41	Tolerated			0.1327	0.1145		-3	-2	-8.3	43.03
c.20C>A	S7Y 2D AIThe SynGAP1 missense variant S7Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.548467	Binding	0.386	0.922	0.750											-5.240	Likely Benign	0.230	Likely Benign	Likely Benign										0.193	Likely Benign	-0.36	Neutral	0.561	Possibly Damaging	0.047	Benign	4.06	Benign	0.00	Affected			0.0708	0.5053		-3	-2	-0.5	76.10
c.2281C>T	R761W 2D AIThe SynGAP1 missense variant R761W is listed in gnomAD (ID 6‑33441746‑C‑T) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the majority of tools (six pathogenic vs. four benign) suggest a pathogenic effect, and this conclusion does not contradict ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250								6-33441746-C-T	1	6.20e-7	-9.248	Likely Pathogenic	0.665	Likely Pathogenic	Likely Benign										0.193	Likely Benign	-3.52	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	2.66	Benign	0.06	Tolerated	3.99	5	0.1018	0.3668		-3	2	3.6	30.03
c.2296T>C	S766P 2D AIThe SynGAP1 missense variant S766P is reported in gnomAD (ID 6‑33442454‑T‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while SIFT uniquely predicts it as pathogenic. The remaining tools, ESM1b and AlphaMissense‑Default, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.405110	Structured	0.923125	Binding	0.338	0.874	0.250								6-33442454-T-C	1	1.28e-6	-7.343	In-Between	0.374	Ambiguous	Likely Benign										0.193	Likely Benign	-0.91	Neutral	0.006	Benign	0.013	Benign	4.07	Benign	0.01	Affected	3.64	6	0.2216	0.5862		-1	1	-0.8	10.04
c.2620C>G	Q874E 2D AIThe SynGAP1 missense variant Q874E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for Q874E, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.576	Likely Benign	0.197	Likely Benign	Likely Benign										0.193	Likely Benign	-1.95	Neutral	0.963	Probably Damaging	0.973	Probably Damaging	2.73	Benign	0.00	Affected			0.1489	0.3577		2	2	0.0	0.98
c.2686G>T	G896C 2D AIThe SynGAP1 missense variant G896C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625											-5.607	Likely Benign	0.245	Likely Benign	Likely Benign										0.193	Likely Benign	-2.59	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.50	Benign	0.10	Tolerated			0.1270	0.4369		-3	-3	2.9	46.09
c.2723A>T	Q908L 2D AIThe SynGAP1 missense variant Q908L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250											-3.589	Likely Benign	0.420	Ambiguous	Likely Benign										0.193	Likely Benign	-1.40	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.53	Benign	0.05	Affected			0.0706	0.5655		-2	-2	7.3	-14.97
c.3116T>C	I1039T 2D AIThe SynGAP1 missense variant I1039T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443668‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only AlphaMissense‑Default predicts a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus remains benign; a Foldetta stability analysis is not available. Overall, the majority of computational evidence supports a benign impact, and this is consistent with the ClinVar “Uncertain” classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.979204	Binding	0.292	0.806	0.625					Uncertain		1	6-33443668-T-C	12	7.43e-6	-2.465	Likely Benign	0.645	Likely Pathogenic	Likely Benign										0.193	Likely Benign	0.45	Neutral	0.004	Benign	0.008	Benign	2.75	Benign	0.10	Tolerated	3.77	5	0.1248	0.2293		-1	0	-5.2	-12.05
c.3401C>A	T1134N 2D AIThe SynGAP1 missense variant T1134N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that T1134N is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.813034	Binding	0.335	0.885	0.875											-4.368	Likely Benign	0.176	Likely Benign	Likely Benign										0.193	Likely Benign	-0.34	Neutral	0.001	Benign	0.001	Benign	5.42	Benign	0.04	Affected			0.1386	0.4870		0	0	-2.8	13.00
c.3698T>A	I1233N 2D AIThe SynGAP1 I1233N missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and FATHMM. All other evaluated tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.564054	Binding	0.881	0.531	0.125											-9.586	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-4.36	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	2.52	Benign	0.00	Affected			0.0879	0.0340		-2	-3	-8.0	0.94
c.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.487T>C	F163L 2D AIThe SynGAP1 missense variant F163L has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, whereas the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, and this assessment does not contradict the ClinVar status, which currently has no classification for F163L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.513928	Binding	0.325	0.686	0.375											-6.380	Likely Benign	0.986	Likely Pathogenic	Likely Pathogenic										0.193	Likely Benign	-1.22	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	4.21	Benign	0.37	Tolerated			0.2191	0.3491		2	0	1.0	-34.02
c.796C>G	L266V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L266V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. FoldX, Rosetta, and Foldetta give uncertain results and are therefore considered unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta is also inconclusive. Consequently, the variant is most likely benign based on the current predictions, and this assessment does not contradict ClinVar, which has no reported status for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.232838	Structured	0.297157	Uncertain	0.948	0.264	0.000											-8.586	Likely Pathogenic	0.153	Likely Benign	Likely Benign	1.71	Ambiguous	0.1	0.97	Ambiguous	1.34	Ambiguous	1.32	Destabilizing	0.193	Likely Benign	-2.20	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.37	Pathogenic	0.11	Tolerated			0.1152	0.2456		2	1	0.4	-14.03
c.1003C>G	R335G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, and SIFT, whereas those that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, 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 uncertain. Overall, more tools predict pathogenicity than benignity, and the high‑accuracy consensus also leans pathogenic. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. 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											-11.860	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous	1.01	Ambiguous	0.1	0.44	Likely Benign	0.73	Ambiguous	0.20	Likely Benign	0.194	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.01	Pathogenic	0.10	Tolerated			0.3000	0.3554		-3	-2	4.1	-99.14
c.1976C>T	S659F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659F is listed in ClinVar with an uncertain significance and is absent from gnomAD. Functional prediction tools that provide definitive calls cluster into two groups: benign predictions come from REVEL, Rosetta, premPS, polyPhen2_HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, SGM Consensus predicts pathogenic, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) yields an uncertain result and is therefore unavailable. Overall, the majority of reliable tools favor a pathogenic effect. Thus, the variant is most likely pathogenic, a conclusion that does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000					Uncertain		1				-10.925	Likely Pathogenic	0.662	Likely Pathogenic	Likely Benign	-0.81	Ambiguous	0.1	-0.25	Likely Benign	-0.53	Ambiguous	0.32	Likely Benign	0.194	Likely Benign	-4.59	Deleterious	0.806	Possibly Damaging	0.171	Benign	3.39	Benign	0.05	Affected	3.38	28	0.0897	0.5828		-3	-2	3.6	60.10	221.3	-61.2	0.0	0.0	0.6	0.4						X		Potentially Benign	In the WT simulations, the hydroxyl group of Ser659, located in a kink in the middle of the long α-helix (res. Ser641-Glu666), forms a hydrogen bond with the carboxylate group of Glu656. However, the phenol ring of the Phe659 side chain cannot form a similar hydrogen bond. Instead, it interacts with the hydrophobic isopropyl side chain of Val555 from the opposing α-helix (res. Ala533-Val560). This residue swap may therefore cause issues during protein folding.
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.2485G>A	E829K 2D AIThe SynGAP1 missense variant E829K is listed in ClinVar as Pathogenic (ClinVar ID 1721258.0) and is not reported in gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only REVEL predicts a benign outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta results are unavailable. Overall, the preponderance of evidence indicates that E829K is most likely pathogenic, and this conclusion aligns with the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375					Pathogenic		1				-7.527	In-Between	0.807	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-2.65	Deleterious	0.994	Probably Damaging	0.900	Possibly Damaging	2.27	Pathogenic	0.00	Affected	3.77	5	0.2400	0.7372		0	1	-0.4	-0.94
c.2542G>C	G848R 2D AIThe SynGAP1 missense variant G848R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G848R, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.563942	Binding	0.287	0.816	0.500											-4.867	Likely Benign	0.761	Likely Pathogenic	Likely Benign										0.194	Likely Benign	-1.05	Neutral	0.977	Probably Damaging	0.856	Possibly Damaging	2.59	Benign	0.03	Affected			0.0952	0.4251		-3	-2	-4.1	99.14
c.2548G>A	G850R 2D AIThe SynGAP1 missense variant G850R is listed in ClinVar with an uncertain significance (ClinVar ID 2042462.0) and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only SIFT predicts a pathogenic effect, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign and the SGM‑Consensus indicating a likely benign outcome; Foldetta, a protein‑folding stability method, did not provide a result for this substitution. Overall, the preponderance of evidence points to a benign impact, which aligns with the ClinVar designation of uncertain significance rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.540897	Binding	0.312	0.820	0.500					Uncertain		1				-5.082	Likely Benign	0.398	Ambiguous	Likely Benign										0.194	Likely Benign	-0.07	Neutral	0.010	Benign	0.010	Benign	4.30	Benign	0.01	Affected	3.77	5	0.1011	0.4476		-3	-2	-4.1	99.14
c.2548G>C	G850R 2D AIThe SynGAP1 missense variant G850R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM‑Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is “Likely Benign.” AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.540897	Binding	0.312	0.820	0.500											-5.082	Likely Benign	0.398	Ambiguous	Likely Benign										0.194	Likely Benign	-0.07	Neutral	0.010	Benign	0.010	Benign	4.30	Benign	0.01	Affected	3.77	5	0.1011	0.4476		-3	-2	-4.1	99.14
c.2609T>C	L870P 2D AIThe SynGAP1 missense variant L870P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.688079	Binding	0.274	0.850	0.125											-4.462	Likely Benign	0.402	Ambiguous	Likely Benign										0.194	Likely Benign	-1.92	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	2.59	Benign	0.13	Tolerated			0.3795	0.1864		-3	-3	-5.4	-16.04
c.2713C>T	R905C 2D AIThe SynGAP1 missense variant R905C (ClinVar ID 469152.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443265‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard predictors indicate a pathogenic impact, whereas the high‑accuracy AlphaMissense‑Optimized tool suggests a benign effect. Consequently, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.618085	Binding	0.291	0.920	0.250					Conflicting		2	6-33443265-C-T	15	9.31e-6	-5.578	Likely Benign	0.723	Likely Pathogenic	Likely Benign										0.194	Likely Benign	-3.14	Deleterious	1.000	Probably Damaging	0.980	Probably Damaging	2.57	Benign	0.01	Affected	3.77	5	0.3231	0.3642		-4	-3	7.0	-53.05
c.2804C>T	A935V 2D AIThe SynGAP1 missense variant A935V is not reported 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 AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs. 1 pathogenic votes). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A935V, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-4.750	Likely Benign	0.397	Ambiguous	Likely Benign										0.194	Likely Benign	-2.06	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.1340	0.5941		0	0	2.4	28.05
c.2812G>T	G938W 2D AIThe SynGAP1 missense variant G938W is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.905695	Disordered	0.949795	Binding	0.318	0.883	0.625											-8.763	Likely Pathogenic	0.604	Likely Pathogenic	Likely Benign										0.194	Likely Benign	-1.71	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.04	Affected			0.0762	0.4008		-7	-2	-0.5	129.16
c.293A>T	H98L 2D AIThe SynGAP1 H98L missense variant is reported in gnomAD (ID 6‑33425901‑A‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for H98L, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.631713	Binding	0.348	0.872	0.625								6-33425901-A-T	1	6.32e-7	-1.804	Likely Benign	0.113	Likely Benign	Likely Benign										0.194	Likely Benign	-0.51	Neutral	0.115	Benign	0.012	Benign	4.24	Benign	0.00	Affected	4.32	1	0.1125	0.6291		-3	-2	7.0	-23.98
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.3613C>G	L1205V 2D AIThe SynGAP1 missense variant L1205V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375											-12.077	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic										0.194	Likely Benign	-2.59	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1388	0.2289		2	1	0.4	-14.03
c.3787A>C	I1263L 2D AIThe SynGAP1 missense variant I1263L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign, two pathogenic). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-1.210	Likely Benign	0.699	Likely Pathogenic	Likely Benign										0.194	Likely Benign	-1.66	Neutral	0.011	Benign	0.022	Benign	1.94	Pathogenic	0.00	Affected			0.0717	0.2890		2	2	-0.7	0.00
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.524A>G	Q175R 2D AIThe SynGAP1 missense variant Q175R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. The only tool that predicts a pathogenic outcome is 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 unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-5.785	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.194	Likely Benign	-1.29	Neutral	0.012	Benign	0.006	Benign	4.14	Benign	0.26	Tolerated			0.1485	0.1352		1	1	-1.0	28.06
c.140G>C	R47P 2D AIThe SynGAP1 missense variant R47P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign) and therefore unavailable as evidence. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant and is likewise unavailable. High‑accuracy tools specifically indicate a benign prediction from AlphaMissense‑Optimized, while the other high‑accuracy methods (SGM Consensus, Foldetta) provide no definitive assessment. Overall, the balance of evidence (five pathogenic vs. four benign predictions) suggests the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125											-10.316	Likely Pathogenic	0.746	Likely Pathogenic	Likely Benign										0.195	Likely Benign	-1.63	Neutral	0.841	Possibly Damaging	0.809	Possibly Damaging	4.02	Benign	0.00	Affected			0.2050	0.4956		0	-2	2.9	-59.07
c.1555G>C	E519Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E519Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect on protein stability. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.078022	Structured	0.104514	Uncertain	0.899	0.328	0.000											-8.693	Likely Pathogenic	0.792	Likely Pathogenic	Ambiguous	-0.35	Likely Benign	0.1	-0.14	Likely Benign	-0.25	Likely Benign	-0.21	Likely Benign	0.195	Likely Benign	-2.48	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	3.28	Benign	0.14	Tolerated			0.1394	0.3418		2	2	0.0	-0.98
c.2255C>T	S752L 2D AIThe SynGAP1 missense variant S752L is listed in ClinVar with an “Uncertain” status (ClinVar ID 2143952.0) and is present in gnomAD (ID 6‑33441720‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.690594	Binding	0.365	0.877	0.625					Uncertain		2	6-33441720-C-T	6	3.72e-6	-3.386	Likely Benign	0.182	Likely Benign	Likely Benign										0.195	Likely Benign	-2.09	Neutral	0.993	Probably Damaging	0.641	Possibly Damaging	1.51	Pathogenic	0.01	Affected	3.99	5	0.1308	0.5909		-3	-2	4.6	26.08
c.2575A>T	S859C 2D AIThe SynGAP1 missense variant S859C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN reports the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do 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		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-8.268	Likely Pathogenic	0.136	Likely Benign	Likely Benign										0.195	Likely Benign	-2.01	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.94	Benign	0.03	Affected			0.1046	0.6153		0	-1	3.3	16.06
c.2585A>T	N862I 2D AIThe SynGAP1 missense variant N862I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; AlphaMissense‑Default is uncertain. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a pathogenic majority (2 pathogenic vs. 1 benign, 1 uncertain). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions support 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.			0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-8.702	Likely Pathogenic	0.561	Ambiguous	Likely Benign										0.195	Likely Benign	-3.19	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	4.03	Benign	0.03	Affected			0.0844	0.6443		-2	-3	8.0	-0.94
c.2945A>G	Y982C 2D AIThe SynGAP1 missense variant Y982C is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443497‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. 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					Conflicting		2	6-33443497-A-G	2	1.24e-6	-6.256	Likely Benign	0.746	Likely Pathogenic	Likely Benign										0.195	Likely Benign	-1.67	Neutral	0.997	Probably Damaging	0.923	Probably Damaging	3.87	Benign	0.00	Affected	4.32	1	0.2988	0.2345		0	-2	3.8	-60.04
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.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.3712C>A	Q1238K 2D AIThe SynGAP1 missense variant Q1238K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-8.631	Likely Pathogenic	0.513	Ambiguous	Likely Benign										0.195	Likely Benign	-1.70	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.51	Benign	0.30	Tolerated			0.1345	0.3494		1	1	-0.4	0.04
c.3739A>G	R1247G 2D AIThe SynGAP1 missense variant R1247G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain and SGM‑Consensus is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-7.920	In-Between	0.724	Likely Pathogenic	Likely Benign										0.195	Likely Benign	-5.58	Deleterious	0.980	Probably Damaging	0.721	Possibly Damaging	1.70	Pathogenic	0.00	Affected			0.3047	0.2327		-3	-2	4.1	-99.14
c.3856G>A	E1286K 2D AIThe SynGAP1 missense variant E1286K is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33447904‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign. Foldetta results are unavailable. Overall, the majority of evidence (5 benign vs. 3 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet classified there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.817022	Binding	0.544	0.765	0.750								6-33447904-G-A			-3.784	Likely Benign	0.395	Ambiguous	Likely Benign										0.195	Likely Benign	-2.36	Neutral	0.770	Possibly Damaging	0.242	Benign	2.47	Pathogenic	0.02	Affected	3.77	5	0.2069	0.5117		1	0	-0.4	-0.94
c.413A>C	K138T 2D AIThe SynGAP1 missense variant K138T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, with no high‑accuracy consensus supporting pathogenicity. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-5.143	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.195	Likely Benign	-3.45	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.01	Affected			0.1940	0.2806		0	-1	3.2	-27.07
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.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.101A>G	Y34C 2D AIThe SynGAP1 missense variant Y34C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized reports Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for Y34C, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-3.730	Likely Benign	0.171	Likely Benign	Likely Benign										0.196	Likely Benign	0.87	Neutral	0.943	Possibly Damaging	0.941	Probably Damaging	4.32	Benign	0.00	Affected			0.3010	0.2719		0	-2	3.8	-60.04
c.1100T>G	L367R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L367R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Those that predict a pathogenic effect are SIFT, FATHMM, and Rosetta. Tools with uncertain or inconclusive results are FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a benign impact, with a minority of pathogenic predictions. The variant’s status is not contradicted by ClinVar, as it is not yet classified there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-6.527	Likely Benign	0.515	Ambiguous	Likely Benign	0.68	Ambiguous	0.4	6.63	Destabilizing	3.66	Destabilizing	0.70	Ambiguous	0.196	Likely Benign	-0.39	Neutral	0.146	Benign	0.057	Benign	1.66	Pathogenic	0.02	Affected			0.1608	0.1173		-3	-2	-8.3	43.03
c.1426T>C	F476L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F476L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and FATHMM, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No other tools provide definitive evidence. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000											-10.109	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	1.00	Ambiguous	0.1	1.04	Ambiguous	1.02	Ambiguous	0.75	Ambiguous	0.196	Likely Benign	-1.10	Neutral	0.997	Probably Damaging	0.978	Probably Damaging	3.53	Benign	0.60	Tolerated	3.40	22	0.1653	0.2916		2	0	1.0	-34.02	235.9	16.1	0.0	0.1	-0.2	0.0	X							Potentially Benign	In the WT simulations, the phenyl ring of Phe476, located at the end of an α-helix (res. Ala461-Phe476), packs with the hydrophobic side chains of Leu482 and Ile483. Additionally, Phe476 stacks with the Arg475 side chain on the preceding α-α loop connecting the two α-helices (res. Ala461-Phe476 and res. Leu489-Glu519) near the GAP-Ras interface.In the variant simulations, Leu476 can maintain hydrophobic packing with neighboring residues, although not as efficiently as the phenylalanine in the WT system. The absence of Phe476/Arg475 stacking weakens the integrity of the α-helix end in the variant simulations. Nonetheless, no large-scale adverse effects are observed in the simulations. Lastly, the potential effect of the residue swap on SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.2104C>G	Q702E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Rosetta and Foldetta give uncertain results. High‑accuracy methods further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign; Foldetta remains inconclusive. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-10.974	Likely Pathogenic	0.230	Likely Benign	Likely Benign	0.48	Likely Benign	0.0	0.72	Ambiguous	0.60	Ambiguous	0.27	Likely Benign	0.196	Likely Benign	-2.27	Neutral	0.989	Probably Damaging	0.930	Probably Damaging	3.55	Benign	0.15	Tolerated			0.1021	0.1609		2	2	0.0	0.98
c.2408A>T	K803I 2D AIThe SynGAP1 K803I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized assessment is uncertain, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no classification for K803I. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.207	Likely Benign	0.894	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.06	Deleterious	0.995	Probably Damaging	0.913	Probably Damaging	2.31	Pathogenic	0.00	Affected			0.1425	0.3889		-2	-3	8.4	-15.01
c.2414T>G	L805R 2D AIThe SynGAP1 missense variant L805R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as likely pathogenic; Foldetta results are unavailable. Overall, the balance of evidence from the broader set of predictors leans toward pathogenicity, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-6.640	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.196	Likely Benign	-3.00	Deleterious	0.927	Possibly Damaging	0.617	Possibly Damaging	2.37	Pathogenic	0.00	Affected			0.1372	0.0908		-3	-2	-8.3	43.03
c.2469C>A	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2469C>G	S823R 2D AIThe SynGAP1 missense variant S823R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.612	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.196	Likely Benign	-3.47	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.0893	0.4046		0	-1	-3.7	69.11
c.2535C>A	D845E 2D AIThe SynGAP1 missense variant D845E is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta stability analysis is unavailable. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. Overall, the balance of evidence points to a pathogenic effect for D845E, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.979	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-2.67	Deleterious	0.992	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1404	0.6998		3	2	0.0	14.03
c.2535C>G	D845E 2D AIThe SynGAP1 missense variant D845E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect for D845E, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500											-6.979	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-2.67	Deleterious	0.992	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.00	Affected			0.1404	0.6998		3	2	0.0	14.03
c.2723A>C	Q908P 2D AIThe SynGAP1 missense variant Q908P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for Q908P, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250											-4.446	Likely Benign	0.151	Likely Benign	Likely Benign										0.196	Likely Benign	-0.59	Neutral	0.996	Probably Damaging	0.992	Probably Damaging	2.51	Benign	0.11	Tolerated			0.2379	0.5121		0	-1	1.9	-31.01
c.3016T>G	Y1006D 2D AIThe SynGAP1 missense variant Y1006D is catalogued in gnomAD (variant ID 6‑33443568‑T‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic impact are PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized is uncertain, and no Foldetta (FoldX‑MD/ Rosetta) stability data are available. Considering the high‑accuracy consensus, the variant is most likely benign; this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.930554	Binding	0.264	0.896	0.750								6-33443568-T-G			-5.296	Likely Benign	0.898	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-1.53	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.73	Benign	0.56	Tolerated	3.77	5	0.3776	0.1094		-3	-4	-2.2	-48.09
c.3353G>C	S1118T 2D AIThe SynGAP1 missense variant S1118T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750											-6.063	Likely Benign	0.067	Likely Benign	Likely Benign										0.196	Likely Benign	-0.67	Neutral	0.790	Possibly Damaging	0.433	Benign	5.18	Benign	0.10	Tolerated			0.2066	0.5587		1	1	0.1	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.3747G>C	R1249S 2D AIThe SynGAP1 missense variant R1249S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and labels the variant as Likely Pathogenic. High‑accuracy assessments are limited: AlphaMissense‑Optimized returns an Uncertain result, and the Foldetta stability analysis is not available for this residue. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because no ClinVar entry exists for R1249S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-6.936	Likely Benign	0.828	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.52	Deleterious	0.980	Probably Damaging	0.828	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2777	0.1843		0	-1	3.7	-69.11
c.3747G>T	R1249S 2D AIThe SynGAP1 missense variant R1249S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and labels the variant as Likely Pathogenic. High‑accuracy assessments are limited: AlphaMissense‑Optimized returns an Uncertain result, and the Foldetta stability analysis is not available for this residue. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because no ClinVar entry exists for R1249S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-6.936	Likely Benign	0.828	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-4.52	Deleterious	0.980	Probably Damaging	0.828	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2777	0.1843		0	-1	3.7	-69.11
c.3893A>C	Q1298P 2D AIThe SynGAP1 missense variant Q1298P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.895297	Binding	0.410	0.821	0.750											-1.819	Likely Benign	0.096	Likely Benign	Likely Benign										0.196	Likely Benign	-2.93	Deleterious	0.586	Possibly Damaging	0.105	Benign	2.76	Benign	0.03	Affected			0.2237	0.4025		0	-1	1.9	-31.01
c.508C>G	R170G 2D AIThe SynGAP1 missense variant R170G is not reported in ClinVar and has no entries in gnomAD. Prediction tools cluster 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, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic impact for R170G, and this conclusion does not conflict with the current ClinVar status, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250											-10.092	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous										0.196	Likely Benign	-3.19	Deleterious	0.664	Possibly Damaging	0.137	Benign	3.88	Benign	0.00	Affected			0.3285	0.3004		-3	-2	4.1	-99.14
c.884C>G	T295S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T295S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; premPS is inconclusive. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority (3 benign vs. 1 pathogenic); and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125											-4.904	Likely Benign	0.335	Likely Benign	Likely Benign	-0.16	Likely Benign	0.2	0.28	Likely Benign	0.06	Likely Benign	0.54	Ambiguous	0.196	Likely Benign	-2.16	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.14	Tolerated			0.3910	0.4473		1	1	-0.1	-14.03
c.1070A>C	H357P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357P missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools give uncertain results: Foldetta (protein‑folding stability) and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-7.953	In-Between	0.267	Likely Benign	Likely Benign	0.17	Likely Benign	0.9	3.52	Destabilizing	1.85	Ambiguous	-0.06	Likely Benign	0.197	Likely Benign	-2.70	Deleterious	0.936	Possibly Damaging	0.469	Possibly Damaging	4.18	Benign	0.17	Tolerated			0.2433	0.4468		0	-2	1.6	-40.02
c.1278C>A	N426K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426K resides in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give inconclusive results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	0.197	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			0.1906	0.2822		1	0	-0.4	14.07
c.1278C>G	N426K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426K is located in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, while those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools report uncertainty: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect on protein stability. Overall, the majority of predictions lean toward pathogenicity, with a split in the most reliable methods. Therefore, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-11.659	Likely Pathogenic	0.867	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.0	0.00	Likely Benign	0.02	Likely Benign	0.54	Ambiguous	0.197	Likely Benign	-3.86	Deleterious	0.998	Probably Damaging	0.978	Probably Damaging	3.38	Benign	0.12	Tolerated			0.1906	0.2822		1	0	-0.4	14.07
c.1998G>C	E666D 2D 3DClick to see structure in 3D Viewer AISynGAP1 E666D is listed in ClinVar with an uncertain significance (ID 587483.0) and is not reported in gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and Rosetta; pathogenic calls come from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as likely pathogenic. High‑accuracy assessments give AlphaMissense‑Optimized a benign prediction, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the balance of evidence slightly favors a pathogenic interpretation, but the predictions are not unequivocal. Thus, the variant is most likely pathogenic according to the current computational data, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000					Uncertain		1				-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.1998G>T	E666D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E666D missense variant is not reported in ClinVar (ClinVar ID: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, Rosetta, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. FoldX alone is also uncertain, so these results are treated as unavailable. Overall, the balance of evidence leans toward a pathogenic impact for E666D, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.086870	Uncertain	0.925	0.387	0.000											-8.820	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.88	Ambiguous	0.0	0.37	Likely Benign	0.63	Ambiguous	1.05	Destabilizing	0.197	Likely Benign	-2.69	Deleterious	0.992	Probably Damaging	0.603	Possibly Damaging	3.43	Benign	0.06	Tolerated	3.38	28	0.1926	0.3092		3	2	0.0	-14.03	237.2	16.5	0.0	0.0	-0.3	0.1		X						Potentially Pathogenic	The carboxylate group of Glu666, located on the α-helix (res. Ser641-Glu666), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), such as Lys566, Thr672, and Asn669, in the WT simulations. In the variant simulations, the shorter side chain of Asp666 cannot maintain these interactions as efficiently as Glu666 in the WT, resulting in a less coordinated hydrogen-bond network.
c.2268G>C	Q756H 2D AIThe SynGAP1 missense variant Q756H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-4.625	Likely Benign	0.276	Likely Benign	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.05	Affected			0.1545	0.4404		3	0	0.3	9.01
c.2268G>T	Q756H 2D AIThe SynGAP1 missense variant Q756H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign based on current computational evidence, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-4.625	Likely Benign	0.276	Likely Benign	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.05	Affected			0.1545	0.4404		3	0	0.3	9.01
c.2276T>C	M759T 2D AIThe SynGAP1 missense variant M759T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the SGM consensus and AlphaMissense‑Optimized—supports a benign classification, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375											-4.202	Likely Benign	0.380	Ambiguous	Likely Benign										0.197	Likely Benign	-1.90	Neutral	0.891	Possibly Damaging	0.315	Benign	2.58	Benign	0.08	Tolerated			0.2063	0.1534		-1	-1	-2.6	-30.09
c.2309A>T	Q770L 2D AIThe SynGAP1 missense variant Q770L 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 SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q770L, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.923732	Binding	0.328	0.887	0.250											-5.524	Likely Benign	0.521	Ambiguous	Likely Benign										0.197	Likely Benign	-2.17	Neutral	0.095	Benign	0.030	Benign	4.14	Benign	0.01	Affected			0.0776	0.6230		-2	-2	7.3	-14.97
c.2482A>G	T828A 2D AIThe SynGAP1 missense variant T828A is reported in gnomAD (variant ID 6‑33443034‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.631236	Binding	0.321	0.879	0.500								6-33443034-A-G	1	6.20e-7	-2.974	Likely Benign	0.340	Likely Benign	Likely Benign										0.197	Likely Benign	-2.13	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.67	Benign	0.24	Tolerated	3.77	5	0.4039	0.3861		0	1	2.5	-30.03
c.2885A>C	H962P 2D AIThe SynGAP1 missense variant H962P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.984483	Binding	0.369	0.886	0.750											-8.419	Likely Pathogenic	0.066	Likely Benign	Likely Benign										0.197	Likely Benign	-0.94	Neutral	0.748	Possibly Damaging	0.170	Benign	4.16	Benign	0.07	Tolerated			0.2011	0.4352		0	-2	1.6	-40.02
c.3466G>T	A1156S 2D AIThe SynGAP1 missense variant A1156S is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33444501‑G‑T). Functional 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. AlphaMissense‑Optimized 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. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500								6-33444501-G-T	1	6.20e-7	-2.052	Likely Benign	0.798	Likely Pathogenic	Ambiguous										0.197	Likely Benign	-2.23	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	1.65	Pathogenic	0.00	Affected	3.77	5	0.2594	0.6154		1	1	-2.6	16.00
c.3695A>T	K1232I 2D AIThe SynGAP1 K1232I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is classified as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-12.225	Likely Pathogenic	0.896	Likely Pathogenic	Ambiguous										0.197	Likely Benign	-5.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.08	Pathogenic	0.00	Affected			0.0778	0.3321		-2	-3	8.4	-15.01
c.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.77G>T	G26V 2D AIThe SynGAP1 missense variant G26V is reported in gnomAD (variant ID 6‑33423486‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicted set includes REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic‑predicted set contains polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No Foldetta stability result is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect for G26V, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375								6-33423486-G-T	1	6.20e-7	-3.499	Likely Benign	0.165	Likely Benign	Likely Benign										0.197	Likely Benign	-2.34	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.89	Benign	0.00	Affected	4.32	1	0.1344	0.4333		-3	-1	4.6	42.08
c.86T>A	M29K 2D AIThe SynGAP1 missense variant M29K is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency or clinical annotation. Prediction tools that converge on a benign outcome include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the collective predictions point to a benign effect, and this conclusion does not contradict the absence of a ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-2.514	Likely Benign	0.287	Likely Benign	Likely Benign										0.197	Likely Benign	-0.88	Neutral	0.018	Benign	0.184	Benign	4.27	Benign	0.00	Affected			0.2019	0.1312		0	-1	-5.8	-3.02
c.158G>A	G53E 2D AIThe SynGAP1 missense variant G53E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.268042	Structured	0.460894	Uncertain	0.386	0.666	0.000											-2.061	Likely Benign	0.853	Likely Pathogenic	Ambiguous										0.198	Likely Benign	-0.25	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	4.29	Benign	0.00	Affected			0.1413	0.4378		0	-2	-3.1	72.06
c.1688G>A	R563K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R563K missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are inconclusive are Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000											-10.948	Likely Pathogenic	0.335	Likely Benign	Likely Benign	0.25	Likely Benign	0.0	0.66	Ambiguous	0.46	Likely Benign	0.70	Ambiguous	0.198	Likely Benign	-2.37	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	3.46	Benign	0.35	Tolerated			0.4434	0.2379		3	2	0.6	-28.01
c.2120C>G	A707G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707G missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) give uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta remains uncertain. Overall, the majority of definitive predictions lean toward a benign effect, and there is no ClinVar status to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-7.480	In-Between	0.224	Likely Benign	Likely Benign	1.45	Ambiguous	0.0	1.52	Ambiguous	1.49	Ambiguous	0.62	Ambiguous	0.198	Likely Benign	-2.60	Deleterious	0.991	Probably Damaging	0.960	Probably Damaging	3.42	Benign	0.01	Affected			0.1678	0.2388		1	0	-2.2	-14.03
c.2336G>T	S779I 2D AIThe SynGAP1 missense variant S779I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy methods give a benign call from AlphaMissense‑Optimized; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-6.261	Likely Benign	0.578	Likely Pathogenic	Likely Benign										0.198	Likely Benign	-2.10	Neutral	0.918	Possibly Damaging	0.827	Possibly Damaging	2.28	Pathogenic	0.05	Affected			0.1046	0.6248		-1	-2	5.3	26.08
c.2570G>T	S857I 2D AIThe SynGAP1 missense variant S857I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S857I, 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		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-7.092	In-Between	0.192	Likely Benign	Likely Benign										0.198	Likely Benign	-0.44	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	4.04	Benign	0.05	Affected			0.1070	0.6208		-1	-2	5.3	26.08
c.2579T>G	V860G 2D AIThe SynGAP1 missense variant V860G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: the benign group includes REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic group contains only SIFT. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from the majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign, while Foldetta results are unavailable. Overall, the collective evidence indicates that V860G is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-3.471	Likely Benign	0.173	Likely Benign	Likely Benign										0.198	Likely Benign	-1.54	Neutral	0.012	Benign	0.009	Benign	4.11	Benign	0.00	Affected			0.2312	0.2547		-1	-3	-4.6	-42.08
c.3011A>G	H1004R 2D AIThe SynGAP1 missense variant H1004R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Benign, and no Foldetta stability data is available. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750											-3.316	Likely Benign	0.813	Likely Pathogenic	Ambiguous										0.198	Likely Benign	-1.88	Neutral	0.997	Probably Damaging	0.994	Probably Damaging	2.77	Benign	0.50	Tolerated			0.2097	0.3132		2	0	-1.3	19.05
c.327T>A	S109R 2D AIThe SynGAP1 missense variant S109R 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, FATHMM, and the SGM‑Consensus (Likely Benign). 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 (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains benign; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, and this is not contradicted by any ClinVar status. 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		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-4.830	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-1.80	Neutral	0.002	Benign	0.001	Benign	3.48	Benign	0.00	Affected			0.0884	0.2700		0	-1	-3.7	69.11
c.327T>G	S109R 2D AIThe SynGAP1 missense variant S109R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict pathogenicity are SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give mixed results: AlphaMissense‑Optimized reports a pathogenic effect, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. Overall, the majority of predictions lean toward a benign impact, with one high‑accuracy tool suggesting pathogenicity, and there is no ClinVar status to contradict these findings. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-4.830	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-1.80	Neutral	0.002	Benign	0.001	Benign	3.48	Benign	0.00	Affected			0.0884	0.2700		0	-1	-3.7	69.11
c.3299G>T	G1100V 2D AIThe SynGAP1 missense variant G1100V is reported in gnomAD (variant ID 6‑33443851‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign); pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the balance of evidence favors a benign classification for G1100V, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875								6-33443851-G-T	1	6.51e-7	-2.362	Likely Benign	0.118	Likely Benign	Likely Benign										0.198	Likely Benign	-2.43	Neutral	0.992	Probably Damaging	0.906	Possibly Damaging	1.93	Pathogenic	0.01	Affected	3.77	5	0.1297	0.4036		-3	-1	4.6	42.08
c.3556T>C	S1186P 2D AIThe SynGAP1 missense variant S1186P lies in a coiled‑coil domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and 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 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the balance of evidence leans toward pathogenicity, with no ClinVar status to contradict this conclusion. 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											-6.365	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-2.51	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	2.64	Benign	0.09	Tolerated			0.1784	0.4006		1	-1	-0.8	10.04
c.3622C>G	R1208G 2D AIThe SynGAP1 missense variant R1208G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375											-12.261	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.198	Likely Benign	-4.66	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.50	Benign	0.01	Affected			0.3287	0.2847		-3	-2	4.1	-99.14
c.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.100T>G	Y34D 2D AIThe SynGAP1 missense variant Y34D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradictory ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-2.653	Likely Benign	0.357	Ambiguous	Likely Benign										0.199	Likely Benign	-1.20	Neutral	0.824	Possibly Damaging	0.828	Possibly Damaging	4.15	Benign	0.00	Affected			0.4092	0.1322		-4	-3	-2.2	-48.09
c.1225A>C	M409L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409L 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 REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. The only inconclusive result is from premPS, which is marked uncertain and does not influence the overall benign consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000											-6.809	Likely Benign	0.286	Likely Benign	Likely Benign	-0.04	Likely Benign	0.2	-0.08	Likely Benign	-0.06	Likely Benign	0.51	Ambiguous	0.199	Likely Benign	-0.84	Neutral	0.206	Benign	0.324	Benign	4.21	Benign	0.57	Tolerated			0.1299	0.4411		4	2	1.9	-18.03
c.1225A>T	M409L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. The only inconclusive result is premPS, which is listed as uncertain and does not influence the overall assessment. High‑accuracy methods confirm the benign prediction: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also classifies it as benign. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000											-6.809	Likely Benign	0.286	Likely Benign	Likely Benign	-0.04	Likely Benign	0.2	-0.08	Likely Benign	-0.06	Likely Benign	0.51	Ambiguous	0.199	Likely Benign	-0.84	Neutral	0.206	Benign	0.324	Benign	4.21	Benign	0.57	Tolerated			0.1299	0.4411		4	2	1.9	-18.03
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.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.2177G>T	R726M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726M has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, Foldetta, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. FoldX is uncertain and is not counted as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of tools and the two high‑accuracy methods predict a benign effect. Therefore, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-8.611	Likely Pathogenic	0.750	Likely Pathogenic	Likely Benign	0.53	Ambiguous	0.1	0.31	Likely Benign	0.42	Likely Benign	0.20	Likely Benign	0.199	Likely Benign	-2.02	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.03	Affected			0.1489	0.4051		0	-1	6.4	-24.99
c.2266C>A	Q756K 2D AIThe SynGAP1 missense variant Q756K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for Q756K, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.458154	Structured	0.806299	Binding	0.340	0.866	0.250											-6.059	Likely Benign	0.340	Likely Benign	Likely Benign										0.199	Likely Benign	-1.47	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.60	Pathogenic	0.21	Tolerated			0.1816	0.4797		1	1	-0.4	0.04
c.2455G>T	A819S 2D AIThe SynGAP1 missense variant A819S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A819S, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.707644	Binding	0.317	0.892	0.625											-3.420	Likely Benign	0.331	Likely Benign	Likely Benign										0.199	Likely Benign	-1.49	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	2.33	Pathogenic	0.27	Tolerated			0.2729	0.6404		1	1	-2.6	16.00
c.2621A>T	Q874L 2D AIThe SynGAP1 missense variant Q874L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant has not been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-6.084	Likely Benign	0.608	Likely Pathogenic	Likely Benign										0.199	Likely Benign	-3.39	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.67	Benign	0.00	Affected			0.0828	0.6595		-2	-2	7.3	-14.97
c.2816C>G	P939R 2D AIThe SynGAP1 missense variant P939R is reported in gnomAD (ID 6‑33443368‑C‑G) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Grouping by consensus, the benign‑predicted tools outnumbered the pathogenic ones by one, but the overall tally favors pathogenicity (5 pathogenic vs 4 benign). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is benign, but the SGM Consensus (a 2‑vs‑2 majority among AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear verdict, and Foldetta data are unavailable. Consequently, the variant is most likely pathogenic according to the available predictions, and this assessment does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.894241	Disordered	0.935841	Binding	0.397	0.897	0.625								6-33443368-C-G	1	6.20e-7	-4.863	Likely Benign	0.260	Likely Benign	Likely Benign										0.199	Likely Benign	-3.79	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.18	Pathogenic	0.00	Affected	3.77	5	0.1360	0.3336		-2	0	-2.9	59.07
c.2935T>G	F979V 2D AIThe SynGAP1 missense variant F979V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for F979V, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625											-3.325	Likely Benign	0.434	Ambiguous	Likely Benign										0.199	Likely Benign	-1.03	Neutral	0.925	Possibly Damaging	0.629	Possibly Damaging	4.21	Benign	0.04	Affected			0.2260	0.3176		-1	-1	1.4	-48.04
c.3371G>C	G1124A 2D AIThe SynGAP1 missense variant G1124A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and the Foldetta stability analysis is unavailable. Taken together, the overwhelming majority of computational evidence classifies G1124A as benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.833401	Binding	0.341	0.931	0.875											-6.608	Likely Benign	0.084	Likely Benign	Likely Benign										0.199	Likely Benign	-0.39	Neutral	0.059	Benign	0.041	Benign	4.81	Benign	0.02	Affected			0.3494	0.5138		1	0	2.2	14.03
c.392G>T	G131V 2D AIThe SynGAP1 missense variant G131V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default) predict a pathogenic impact. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a tie and is therefore unavailable, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no result for this variant. Overall, the balance of evidence favors a pathogenic classification, and this assessment does not contradict any existing ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.724779	Binding	0.302	0.891	0.250											-6.248	Likely Benign	0.795	Likely Pathogenic	Ambiguous										0.199	Likely Benign	-4.25	Deleterious	0.983	Probably Damaging	0.559	Possibly Damaging	3.92	Benign	0.00	Affected			0.1168	0.4175		-1	-3	4.6	42.08
c.77G>A	G26E 2D AIThe SynGAP1 missense variant G26E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375											-3.966	Likely Benign	0.481	Ambiguous	Likely Benign										0.199	Likely Benign	-2.08	Neutral	0.994	Probably Damaging	0.986	Probably Damaging	3.90	Benign	0.00	Affected			0.1623	0.4238		0	-2	-3.1	72.06
c.86T>C	M29T 2D AIThe SynGAP1 missense variant M29T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that M29T is most likely benign, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250					Uncertain		1				-2.167	Likely Benign	0.122	Likely Benign	Likely Benign										0.199	Likely Benign	-0.37	Neutral	0.018	Benign	0.184	Benign	4.33	Benign	0.00	Affected	4.32	1	0.2633	0.2716		-1	-1	-2.6	-30.09
c.1501A>G	I501V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions from FoldX, Rosetta, and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for I501V, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-2.326	Likely Benign	0.083	Likely Benign	Likely Benign	0.94	Ambiguous	0.0	0.56	Ambiguous	0.75	Ambiguous	0.06	Likely Benign	0.200	Likely Benign	0.20	Neutral	0.951	Possibly Damaging	0.960	Probably Damaging	3.52	Benign	1.00	Tolerated			0.0985	0.2491		4	3	-0.3	-14.03
c.1600T>A	S534T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Thus, the overall evidence strongly supports a benign classification, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000											-4.925	Likely Benign	0.104	Likely Benign	Likely Benign	0.10	Likely Benign	0.1	0.46	Likely Benign	0.28	Likely Benign	0.19	Likely Benign	0.200	Likely Benign	-2.42	Neutral	0.676	Possibly Damaging	0.933	Probably Damaging	3.32	Benign	0.07	Tolerated			0.1238	0.5064		1	1	0.1	14.03
c.2112C>A	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, the SGM Consensus confirms Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result, providing no additional evidence. Overall, the preponderance of evidence from multiple independent predictors indicates that S704R is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.200	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
c.2112C>G	S704R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). FoldX and Rosetta give uncertain results, and Foldetta (a combined FoldX‑MD/Rosetta stability assessment) is also uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic; this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-9.417	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.81	Ambiguous	0.1	0.92	Ambiguous	0.87	Ambiguous	0.31	Likely Benign	0.200	Likely Benign	-2.65	Deleterious	0.997	Probably Damaging	0.822	Possibly Damaging	3.53	Benign	0.05	Affected			0.0714	0.3038		0	-1	-3.7	69.11
c.2177G>C	R726T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default; FoldX is uncertain. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-5.249	Likely Benign	0.661	Likely Pathogenic	Likely Benign	0.82	Ambiguous	0.0	-0.11	Likely Benign	0.36	Likely Benign	-0.01	Likely Benign	0.200	Likely Benign	-0.90	Neutral	1.000	Probably Damaging	0.997	Probably Damaging	2.74	Benign	1.00	Tolerated			0.1685	0.4569		-1	-1	3.8	-55.08
c.2234C>A	P745H 2D AIThe SynGAP1 missense variant P745H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875											-5.569	Likely Benign	0.120	Likely Benign	Likely Benign										0.200	Likely Benign	-2.84	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.53	Benign	0.00	Affected			0.1912	0.3403		0	-2	-1.6	40.02
c.2306T>C	L769P 2D AIThe SynGAP1 missense variant L769P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.261	Likely Benign	0.338	Likely Benign	Likely Benign										0.200	Likely Benign	-1.75	Neutral	0.925	Possibly Damaging	0.427	Benign	3.90	Benign	0.00	Affected			0.3573	0.1323		-3	-3	-5.4	-16.04
c.2621A>G	Q874R 2D AIThe SynGAP1 missense variant Q874R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts a benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250											-4.834	Likely Benign	0.527	Ambiguous	Likely Benign										0.200	Likely Benign	-2.33	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.69	Benign	0.00	Affected			0.1619	0.2924		1	1	-1.0	28.06
c.2668C>T	R890C 2D AIThe SynGAP1 missense variant R890C is listed in ClinVar as benign and is present in gnomAD (6-33443220-C‑T). Functional prediction tools show mixed results: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus also indicates benign; Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence leans toward a benign effect, which is consistent with the ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625					Benign		1	6-33443220-C-T	9	5.58e-6	-5.786	Likely Benign	0.402	Ambiguous	Likely Benign										0.200	Likely Benign	-3.38	Deleterious	1.000	Probably Damaging	0.971	Probably Damaging	3.94	Benign	0.04	Affected	4.32	4	0.3626	0.2206		-4	-3	7.0	-53.05
c.2872C>G	H958D 2D AIThe SynGAP1 missense variant H958D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and ESM1b—suggest a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.976011	Binding	0.371	0.913	0.750											-11.494	Likely Pathogenic	0.227	Likely Benign	Likely Benign										0.200	Likely Benign	-0.55	Neutral	0.925	Possibly Damaging	0.232	Benign	4.16	Benign	0.55	Tolerated			0.2732	0.2866		1	-1	-0.3	-22.05
c.3076G>T	D1026Y 2D AIThe SynGAP1 missense variant D1026Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500											-6.999	Likely Benign	0.892	Likely Pathogenic	Ambiguous										0.200	Likely Benign	-3.08	Deleterious	0.938	Possibly Damaging	0.596	Possibly Damaging	2.47	Pathogenic	0.00	Affected			0.0676	0.4936		-4	-3	2.2	48.09
c.311G>C	R104P 2D AIThe SynGAP1 missense variant R104P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.678998	Binding	0.339	0.869	0.625											-3.184	Likely Benign	0.510	Ambiguous	Likely Benign										0.200	Likely Benign	-0.88	Neutral	0.947	Possibly Damaging	0.410	Benign	4.01	Benign	0.00	Affected			0.1759	0.4498		0	-2	2.9	-59.07
c.326G>T	S109I 2D AIThe SynGAP1 missense variant S109I is not 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, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence (five benign vs. three pathogenic predictions) points toward a benign impact. This conclusion does not contradict ClinVar, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-5.195	Likely Benign	0.927	Likely Pathogenic	Ambiguous										0.200	Likely Benign	-2.56	Deleterious	0.267	Benign	0.039	Benign	3.47	Benign	0.00	Affected			0.0910	0.4930		-1	-2	5.3	26.08
c.3425C>A	S1142Y 2D AIThe SynGAP1 missense variant S1142Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, but the single high‑accuracy benign prediction and the inconclusive consensus temper this view. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.719935	Binding	0.276	0.844	1.000											-6.146	Likely Benign	0.569	Likely Pathogenic	Likely Benign										0.200	Likely Benign	-3.39	Deleterious	0.971	Probably Damaging	0.876	Possibly Damaging	2.64	Benign	0.00	Affected			0.0849	0.5429		-3	-2	-0.5	76.10
c.475A>T	I159F 2D AIThe SynGAP1 missense variant I159F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence, particularly from the high‑accuracy tools, points to a benign 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.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-9.530	Likely Pathogenic	0.447	Ambiguous	Likely Benign										0.200	Likely Benign	-1.41	Neutral	0.995	Probably Damaging	0.979	Probably Damaging	3.87	Benign	0.00	Affected			0.0490	0.2446		1	0	-1.7	34.02
c.599T>G	L200W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L200W 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 (SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and Foldetta) predict a pathogenic impact. Two tools (AlphaMissense‑Optimized and Rosetta) provide inconclusive results and are treated as unavailable. 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 Pathogenic, the latter integrating stability predictions from FoldX‑MD and Rosetta. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125											-11.550	Likely Pathogenic	0.824	Likely Pathogenic	Ambiguous	2.90	Destabilizing	1.0	1.95	Ambiguous	2.43	Destabilizing	1.20	Destabilizing	0.200	Likely Benign	-2.93	Deleterious	0.999	Probably Damaging	0.970	Probably Damaging	3.98	Benign	0.02	Affected			0.0627	0.2893		-2	-2	-4.7	73.05
c.85A>C	M29L 2D AIThe SynGAP1 missense variant M29L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-1.633	Likely Benign	0.079	Likely Benign	Likely Benign										0.200	Likely Benign	-0.49	Neutral	0.006	Benign	0.039	Benign	4.27	Benign	0.00	Affected			0.1984	0.5336		4	2	1.9	-18.03
c.85A>T	M29L 2D AIThe SynGAP1 missense variant M29L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect; there is no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-1.633	Likely Benign	0.079	Likely Benign	Likely Benign										0.200	Likely Benign	-0.49	Neutral	0.006	Benign	0.039	Benign	4.27	Benign	0.00	Affected			0.1984	0.5336		4	2	1.9	-18.03
c.1209A>C	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. 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 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	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.1209A>T	K403N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized) predict a pathogenic impact. Predictions from FoldX, Foldetta, and premPS are uncertain or inconclusive and are treated as unavailable. 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 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	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-10.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.87	Ambiguous	0.1	0.41	Likely Benign	1.14	Ambiguous	0.74	Ambiguous	0.201	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.73	Benign	0.05	Affected			0.3374	0.2492		1	0	0.4	-14.07
c.139C>T	R47W 2D AIThe SynGAP1 missense variant R47W is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33423548‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split; Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) indicate a pathogenic impact. 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.			0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125								6-33423548-C-T	1	6.20e-7	-9.201	Likely Pathogenic	0.752	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-2.17	Neutral	0.994	Probably Damaging	0.919	Probably Damaging	4.00	Benign	0.00	Affected	4.32	1	0.1101	0.4158		-3	2	3.6	30.03
c.1594A>C	T532P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T532P is listed in ClinVar as Benign (ClinVar ID 1598909.0) and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus, and Foldetta (combining FoldX‑MD and Rosetta outputs)—all indicate a benign impact. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.275179	Structured	0.021478	Uncertain	0.889	0.385	0.000					Benign		1				-2.143	Likely Benign	0.061	Likely Benign	Likely Benign	-0.30	Likely Benign	0.2	0.06	Likely Benign	-0.12	Likely Benign	0.08	Likely Benign	0.201	Likely Benign	-0.90	Neutral	0.005	Benign	0.008	Benign	-1.28	Pathogenic	0.18	Tolerated	3.37	35	0.1850	0.3811		0	-1	-0.9	-3.99	174.2	35.1	0.4	0.0	0.1	0.0						X		Potentially Benign	Thr532 is located on an α-α loop between the two α-helices (res. Gly502-Tyr518 and Ala533-Val560) facing the membrane. In the WT simulations, the hydroxyl group of Thr532 occasionally forms hydrogen bonds with the backbone atoms of other loop residues without any specific interaction. In the variant simulations, the Pro532 residue swap does not cause structural changes. Although hydrophilic residues seem more favorable in the loop, the pyrrolidine side chain of proline is well suited for unstructured protein regions such as loops. However, due to its location at the SynGAP-membrane interface, the effect of the residue swap cannot be fully addressed using the SynGAP solvent-only simulations.
c.161A>T	N54I 2D AIThe SynGAP1 missense variant N54I is not reported 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. Tools 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, a protein‑folding stability method, has no available result for this variant. Overall, the majority of available predictions (five pathogenic vs. three benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000											-9.919	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.201	Likely Benign	-1.70	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.15	Benign	0.00	Affected			0.0637	0.6793		-2	-3	8.0	-0.94
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.2282G>C	R761P 2D AIThe SynGAP1 missense variant R761P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441747‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions point to a benign impact, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250					Uncertain		3	6-33441747-G-C	1	6.20e-7	-5.091	Likely Benign	0.640	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-1.89	Neutral	0.999	Probably Damaging	0.968	Probably Damaging	2.69	Benign	0.38	Tolerated	3.99	5	0.1998	0.4449		0	-2	2.9	-59.07
c.2449T>C	S817P 2D AIThe SynGAP1 missense variant S817P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools and the consensus score indicate a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-4.633	Likely Benign	0.724	Likely Pathogenic	Likely Benign										0.201	Likely Benign	-3.26	Deleterious	0.999	Probably Damaging	0.966	Probably Damaging	2.39	Pathogenic	0.00	Affected			0.2272	0.6023		1	-1	-0.8	10.04
c.2463C>G	C821W 2D AIThe SynGAP1 missense variant C821W is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (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 evaluated predictors (six pathogenic vs three benign) indicate a pathogenic impact. This prediction is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750											-4.843	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.201	Likely Benign	-3.30	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.64	Benign	0.01	Affected			0.1742	0.3268		-8	-2	-3.4	83.07
c.3356G>C	G1119A 2D AIThe SynGAP1 missense variant G1119A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.818538	Binding	0.339	0.928	0.875											-6.703	Likely Benign	0.082	Likely Benign	Likely Benign										0.201	Likely Benign	-0.33	Neutral	0.393	Benign	0.187	Benign	3.93	Benign	1.00	Tolerated			0.3591	0.4957		1	0	2.2	14.03
c.3511G>A	A1171T 2D AIThe SynGAP1 missense variant A1171T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in‑silico predictors classify the change as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a “Likely Benign” outcome. No tool predicts pathogenicity. High‑accuracy assessments confirm the benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500					Uncertain		1				-3.658	Likely Benign	0.149	Likely Benign	Likely Benign										0.201	Likely Benign	-0.48	Neutral	0.245	Benign	0.138	Benign	5.45	Benign	0.07	Tolerated	4.32	4	0.1421	0.5465		1	0	-2.5	30.03
c.3712C>G	Q1238E 2D AIThe SynGAP1 missense variant Q1238E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically show AlphaMissense‑Optimized predicting benign, while SGM Consensus and Foldetta are unavailable. Overall, the majority of standard predictors (5 pathogenic vs 4 benign) lean toward a pathogenic interpretation, and this assessment does not contradict ClinVar status because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-10.421	Likely Pathogenic	0.312	Likely Benign	Likely Benign										0.201	Likely Benign	-1.90	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.37	Pathogenic	0.02	Affected			0.1078	0.1921		2	2	0.0	0.98
c.3881C>G	A1294G 2D AIThe SynGAP1 missense variant A1294G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy predictors (AlphaMissense‑Optimized) indicate a benign outcome, while the consensus of other tools is split. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.895011	Binding	0.565	0.806	0.625											-3.242	Likely Benign	0.132	Likely Benign	Likely Benign										0.201	Likely Benign	-3.06	Deleterious	0.992	Probably Damaging	0.983	Probably Damaging	2.15	Pathogenic	0.00	Affected			0.1980	0.2695		1	0	-2.2	-14.03
c.673T>G	S225A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S225A is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. The high‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive (uncertain) and therefore does not alter the overall benign assessment. Consequently, the variant is most likely benign based on the available predictions, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.150080	Structured	0.344191	Uncertain	0.817	0.319	0.250											-3.752	Likely Benign	0.052	Likely Benign	Likely Benign	0.31	Likely Benign	0.3	0.79	Ambiguous	0.55	Ambiguous	0.11	Likely Benign	0.201	Likely Benign	-1.52	Neutral	0.001	Benign	0.001	Benign	5.79	Benign	0.58	Tolerated			0.4840	0.5897		1	1	2.6	-16.00
c.886T>A	S296T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S296T missense variant is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors shows a split: six tools (REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT) and AlphaMissense‑Optimized predict a benign effect, whereas four tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default) predict pathogenicity. ESM1b remains uncertain. High‑accuracy assessments give a more definitive picture: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a benign outcome. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250											-7.020	In-Between	0.645	Likely Pathogenic	Likely Benign	0.09	Likely Benign	0.4	0.38	Likely Benign	0.24	Likely Benign	0.19	Likely Benign	0.201	Likely Benign	-2.10	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.13	Pathogenic	0.13	Tolerated			0.1437	0.6340		1	1	0.1	14.03
c.1121C>T	S374F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 S374F missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv and SIFT. Uncertain or inconclusive results are reported for FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus also indicates a likely benign outcome, while Foldetta’s stability analysis remains uncertain. Overall, the majority of evidence points to a benign effect, 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 Benign	C2	0.642678	Disordered	0.428948	Uncertain	0.333	0.812	0.625											-7.907	In-Between	0.268	Likely Benign	Likely Benign	0.55	Ambiguous	0.8	0.60	Ambiguous	0.58	Ambiguous	-0.19	Likely Benign	0.202	Likely Benign	-1.19	Neutral	0.875	Possibly Damaging	0.271	Benign	6.29	Benign	0.00	Affected			0.1045	0.6427		-3	-2	3.6	60.10
c.1380G>C	K460N 2D AIThe SynGAP1 missense variant K460N 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, SIFT, and FATHMM, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic signal: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic; and the protein‑folding stability method Foldetta, which integrates FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the balance of evidence—six pathogenic versus five benign predictions, a pathogenic SGM Consensus, and a pathogenic AlphaMissense‑Optimized—suggests that K460N is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant is not currently catalogued there. 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											-11.988	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.5	0.45	Likely Benign	0.35	Likely Benign	0.89	Ambiguous	0.202	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.06	Tolerated			0.3669	0.1599		1	0	0.4	-14.07
c.1380G>T	K460N 2D AIThe SynGAP1 K460N missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus methods further support a pathogenic interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic; whereas Foldetta, which integrates FoldX‑MD and Rosetta outputs, indicates a benign effect. Overall, the majority of evidence—including the high‑accuracy tools—points to a pathogenic impact for K460N. 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	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-11.988	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.5	0.45	Likely Benign	0.35	Likely Benign	0.89	Ambiguous	0.202	Likely Benign	-4.13	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.06	Tolerated			0.3669	0.1599		1	0	0.4	-14.07
c.1994A>C	Y665S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans pathogenic, and Foldetta is uncertain (treated as unavailable). Overall, the balance of evidence, particularly the pathogenic signal from the SGM Consensus and the equal split among standard predictors, indicates that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-9.110	Likely Pathogenic	0.453	Ambiguous	Likely Benign	1.24	Ambiguous	0.2	1.40	Ambiguous	1.32	Ambiguous	0.87	Ambiguous	0.202	Likely Benign	-2.50	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.55	Benign	0.62	Tolerated			0.3995	0.1793		-3	-2	0.5	-76.10
c.2428C>G	R810G 2D AISynGAP1 missense variant R810G is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: a single benign call from REVEL, and six pathogenic calls from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Two tools (ESM1b and AlphaMissense‑Optimized) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized remains uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic impact for R810G, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.486429	Structured	0.851848	Binding	0.263	0.907	0.375											-7.190	In-Between	0.828	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-3.57	Deleterious	0.996	Probably Damaging	0.925	Probably Damaging	2.35	Pathogenic	0.01	Affected			0.3686	0.4207		-3	-2	4.1	-99.14
c.2467A>G	S823G 2D AIThe SynGAP1 missense variant S823G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the Foldetta stability analysis is unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.034	Likely Benign	0.822	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.2855	0.5287		1	0	0.4	-30.03
c.2488C>G	P830A 2D AIThe SynGAP1 missense variant P830A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which contains no entry for P830A. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.618152	Binding	0.333	0.874	0.500											-4.471	Likely Benign	0.146	Likely Benign	Likely Benign										0.202	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.82	Benign	0.04	Affected			0.3534	0.5050		1	-1	3.4	-26.04
c.2588T>C	L863P 2D AIThe SynGAP1 missense variant L863P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-4.760	Likely Benign	0.234	Likely Benign	Likely Benign										0.202	Likely Benign	-0.78	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.01	Benign	0.12	Tolerated			0.3520	0.1458		-3	-3	-5.4	-16.04
c.2963T>G	L988R 2D AIThe SynGAP1 missense variant L988R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750											-4.412	Likely Benign	0.681	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-2.39	Neutral	0.954	Possibly Damaging	0.867	Possibly Damaging	2.69	Benign	0.00	Affected			0.1257	0.1088		-3	-2	-8.3	43.03
c.3253C>T	R1085W 2D AISynGAP1 missense variant R1085W is listed in ClinVar as Uncertain and is present in gnomAD (ID 6‑33443805‑C‑T). Prediction tools that classify the variant as benign include REVEL, ESM1b, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta stability assessment are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, which contradicts the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000					Uncertain		1	6-33443805-C-T	2	1.26e-6	-6.339	Likely Benign	0.821	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-3.15	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.70	Benign	0.00	Affected	3.77	5	0.1238	0.3700		-3	2	3.6	30.03
c.3397A>C	I1133L 2D AIThe SynGAP1 missense variant I1133L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that I1133L is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.832785	Binding	0.316	0.892	0.750											-1.147	Likely Benign	0.107	Likely Benign	Likely Benign										0.202	Likely Benign	-0.26	Neutral	0.000	Benign	0.001	Benign	5.48	Benign	0.23	Tolerated			0.0911	0.4302		2	2	-0.7	0.00
c.3644A>T	K1215M 2D AIThe SynGAP1 missense variant K1215M is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the preponderance of computational evidence indicates that K1215M is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-11.140	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic										0.202	Likely Benign	-4.06	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.35	Pathogenic	0.00	Affected			0.0922	0.3085		0	-1	5.8	3.02
c.3714G>C	Q1238H 2D AIThe SynGAP1 missense variant Q1238H is reported in gnomAD (variant ID 6‑33446706‑G‑C) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and AlphaMissense‑Optimized, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar classification (none exists). Thus, based on current predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250								6-33446706-G-C	1	6.20e-7	-8.647	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.01	Affected	3.77	5	0.1007	0.3004		0	3	0.3	9.01
c.3714G>T	Q1238H 2D AIThe SynGAP1 missense variant Q1238H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all indicate a pathogenic impact. High‑accuracy assessments further support this dichotomy: AlphaMissense‑Optimized classifies the variant as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as Likely Pathogenic. No Foldetta stability prediction is available. Overall, the preponderance of evidence from multiple independent tools points to a pathogenic effect for Q1238H. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250											-8.647	Likely Pathogenic	0.757	Likely Pathogenic	Likely Benign										0.202	Likely Benign	-3.49	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	2.31	Pathogenic	0.01	Affected	3.77	5	0.1007	0.3004		0	3	0.3	9.01
c.3875T>A	L1292H 2D AIThe SynGAP1 missense variant L1292H is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33447923‑T‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are split, with a slight tilt toward pathogenicity (five pathogenic vs. four benign). Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625								6-33447923-T-A			-5.692	Likely Benign	0.335	Likely Benign	Likely Benign										0.202	Likely Benign	-4.42	Deleterious	0.992	Probably Damaging	0.820	Possibly Damaging	2.46	Pathogenic	0.00	Affected	3.77	5	0.1271	0.0649		-3	-2	-7.0	23.98
c.4010T>A	F1337Y 2D AIThe SynGAP1 missense variant F1337Y is not reported 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 as Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence, including the SGM‑Consensus and the majority of individual predictors, leans toward a benign interpretation. 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		0.823549	Disordered	0.979265	Binding	0.388	0.712	0.625											-3.481	Likely Benign	0.855	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-1.80	Neutral	0.947	Possibly Damaging	0.899	Possibly Damaging	2.82	Benign	0.00	Affected			0.1722	0.2754		7	3	-4.1	16.00
c.523C>A	Q175K 2D AIThe SynGAP1 missense variant Q175K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized remains uncertain, SGM‑Consensus is benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for Q175K, 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		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375											-5.908	Likely Benign	0.826	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-0.89	Neutral	0.118	Benign	0.039	Benign	4.18	Benign	0.37	Tolerated			0.1655	0.3723		1	1	-0.4	0.04
c.89A>C	H30P 2D AIThe SynGAP1 H30P missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.438063	Uncertain	0.373	0.883	0.250											-1.933	Likely Benign	0.077	Likely Benign	Likely Benign										0.202	Likely Benign	-2.77	Deleterious	0.676	Possibly Damaging	0.599	Possibly Damaging	3.89	Benign	0.00	Affected			0.2527	0.4723		0	-2	1.6	-40.02
c.1070A>T	H357L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357L 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, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv, while polyPhen‑2 HumVar and ESM1b are benign or uncertain, respectively. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (3 benign vs 1 pathogenic), and Foldetta also predicts benign. No predictions are missing or inconclusive. Overall, the variant is most likely benign based on the majority of computational evidence, 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.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-7.281	In-Between	0.140	Likely Benign	Likely Benign	-0.18	Likely Benign	0.1	0.14	Likely Benign	-0.02	Likely Benign	0.10	Likely Benign	0.203	Likely Benign	-3.39	Deleterious	0.704	Possibly Damaging	0.169	Benign	4.20	Benign	0.25	Tolerated			0.1084	0.5971		-2	-3	7.0	-23.98
c.116A>G	Y39C 2D AIThe SynGAP1 missense variant Y39C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.432876	Uncertain	0.343	0.787	0.375											-3.109	Likely Benign	0.123	Likely Benign	Likely Benign										0.203	Likely Benign	-2.00	Neutral	0.943	Possibly Damaging	0.941	Probably Damaging	3.96	Benign	0.00	Affected			0.3007	0.2849		0	-2	3.8	-60.04
c.1204C>G	L402V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign; the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a benign outcome. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is therefore not considered evidence for pathogenicity. In summary, all available predictions support a benign classification for the L402V variant, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000											-3.467	Likely Benign	0.105	Likely Benign	Likely Benign	1.91	Ambiguous	0.1	0.78	Ambiguous	1.35	Ambiguous	-0.11	Likely Benign	0.203	Likely Benign	0.18	Neutral	0.004	Benign	0.004	Benign	4.01	Benign	0.29	Tolerated			0.1807	0.3657		2	1	0.4	-14.03
c.1417G>A	V473I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V473I is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33438449‑G‑A). Functional prediction tools that agree on benign impact include REVEL, FoldX, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Pathogenic predictions are provided by both polyPhen‑2 HumDiv and HumVar. Predictions that are inconclusive are AlphaMissense‑Default, ESM1b, Foldetta, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is unavailable due to no majority, and Foldetta is uncertain. Overall, the balance of evidence favors a benign effect for V473I, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.191378	Structured	0.362529	Uncertain	0.884	0.239	0.000					Uncertain		1	6-33438449-G-A	1	6.20e-7	-7.481	In-Between	0.418	Ambiguous	Likely Benign	-0.12	Likely Benign	0.0	1.20	Ambiguous	0.54	Ambiguous	-0.06	Likely Benign	0.203	Likely Benign	-0.91	Neutral	0.929	Possibly Damaging	0.917	Probably Damaging	3.74	Benign	0.18	Tolerated	3.37	34	0.0568	0.3335		3	4	0.3	14.03
c.1600T>C	S534P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534P is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438843‑T‑C). Functional prediction tools that report a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy assessments are consistent with a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the aggregate predictions, the variant is most likely benign, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000					Uncertain		1	6-33438843-T-C	3	1.86e-6	-5.056	Likely Benign	0.265	Likely Benign	Likely Benign	-0.40	Likely Benign	0.2	0.35	Likely Benign	-0.03	Likely Benign	0.47	Likely Benign	0.203	Likely Benign	-3.81	Deleterious	0.993	Probably Damaging	0.993	Probably Damaging	3.32	Benign	0.05	Affected	3.37	35	0.2071	0.4650		-1	1	-0.8	10.04
c.1817G>C	S606T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and AlphaMissense‑Optimized, whereas a pathogenic consensus is reached by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain results come from Rosetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools predict pathogenicity, and the SGM Consensus supports this view, while the high‑accuracy methods give mixed results. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-11.052	Likely Pathogenic	0.554	Ambiguous	Likely Benign	0.06	Likely Benign	0.1	-0.91	Ambiguous	-0.43	Likely Benign	0.57	Ambiguous	0.203	Likely Benign	-2.99	Deleterious	0.826	Possibly Damaging	0.933	Probably Damaging	3.34	Benign	0.03	Affected			0.1260	0.4513		1	1	0.1	14.03
c.2233C>A	P745T 2D AIThe SynGAP1 missense variant P745T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875											-5.119	Likely Benign	0.071	Likely Benign	Likely Benign										0.203	Likely Benign	-2.78	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.52	Benign	0.02	Affected			0.1657	0.4593		0	-1	0.9	3.99
c.2354G>C	R785P 2D AIThe SynGAP1 missense variant R785P is catalogued in gnomAD (6‑33442906‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the balance of evidence, with seven pathogenic versus three benign predictions and a pathogenic consensus from SGM, indicates that R785P is most likely pathogenic. This conclusion does not contradict ClinVar, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.859585	Disordered	0.681730	Binding	0.325	0.896	0.625								6-33442906-G-C			-3.603	Likely Benign	0.721	Likely Pathogenic	Likely Benign										0.203	Likely Benign	-4.12	Deleterious	0.998	Probably Damaging	0.958	Probably Damaging	2.24	Pathogenic	0.01	Affected	3.64	6	0.2370	0.4485		-2	0	2.9	-59.07
c.2452C>T	P818S 2D AIThe SynGAP1 missense variant P818S is catalogued in gnomAD (ID 6‑33443004‑C‑T) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments are limited: AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. Taken together, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625								6-33443004-C-T	1	6.20e-7	-5.740	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-4.38	Deleterious	0.989	Probably Damaging	0.824	Possibly Damaging	2.04	Pathogenic	0.04	Affected	3.77	5	0.3581	0.6199		-1	1	0.8	-10.04
c.2921A>G	D974G 2D AIThe SynGAP1 missense variant D974G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, 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 Benign		0.879233	Disordered	0.964377	Binding	0.389	0.897	0.625											-1.638	Likely Benign	0.188	Likely Benign	Likely Benign										0.203	Likely Benign	-0.72	Neutral	0.036	Benign	0.026	Benign	4.18	Benign	0.06	Tolerated			0.3379	0.6771		1	-1	3.1	-58.04
c.2955T>A	S985R 2D AIThe SynGAP1 missense variant S985R has no ClinVar entry and is not reported in gnomAD. 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 reports a likely benign outcome. Pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (a majority‑vote aggregator) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are evenly divided, leaving the variant’s clinical significance uncertain; it does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-6.148	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.203	Likely Benign	-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected			0.1213	0.3905		0	-1	-3.7	69.11
c.2955T>G	S985R 2D AISynGAP1 missense variant S985R has no ClinVar record and is not present in gnomAD. Computational predictions are mixed: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy tools give a split result: AlphaMissense‑Optimized predicts pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely benign; Foldetta data are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal number of benign and pathogenic scores. No ClinVar evidence contradicts these predictions. Thus, the variant is best classified as of uncertain significance, with no clear bias toward benign or pathogenic status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-6.148	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic										0.203	Likely Benign	-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected			0.1213	0.3905		0	-1	-3.7	69.11
c.3023A>G	D1008G 2D AIThe SynGAP1 D1008G missense variant (ClinVar ID 2963386.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443575‑A‑G). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, which does not contradict the current ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625					Uncertain		1	6-33443575-A-G	1	6.20e-7	-3.213	Likely Benign	0.742	Likely Pathogenic	Likely Benign										0.203	Likely Benign	-2.84	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.65	Benign	0.01	Affected	3.77	5	0.3660	0.6073		-1	1	3.1	-58.04
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.3692G>T	S1231I 2D AIThe SynGAP1 missense variant S1231I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains likely pathogenic; Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification for S1231I, and this conclusion does not contradict any existing ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.490133	Structured	0.519419	Binding	0.876	0.544	0.250											-9.360	Likely Pathogenic	0.712	Likely Pathogenic	Likely Benign										0.203	Likely Benign	-3.24	Deleterious	0.966	Probably Damaging	0.690	Possibly Damaging	2.64	Benign	0.04	Affected			0.0701	0.4550		-1	-2	5.3	26.08
c.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.553T>G	S185A 2D AIThe SynGAP1 missense variant S185A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. High‑accuracy assessments therefore show a likely pathogenic consensus from SGM‑Consensus, with no contradictory evidence from ClinVar or population databases. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.545602	Disordered	0.430485	Uncertain	0.365	0.623	0.500											-11.839	Likely Pathogenic	0.868	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-2.57	Deleterious	0.231	Benign	0.107	Benign	3.65	Benign	0.00	Affected			0.5147	0.4472	Weaken	1	1	2.6	-16.00
c.864C>A	D288E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Two tools give uncertain results: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-6.685	Likely Benign	0.350	Ambiguous	Likely Benign	0.10	Likely Benign	0.0	0.74	Ambiguous	0.42	Likely Benign	-0.10	Likely Benign	0.203	Likely Benign	-2.84	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.74	Pathogenic	0.13	Tolerated			0.1559	0.5476		3	2	0.0	14.03
c.864C>G	D288E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D288E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Two tools give uncertain results: Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.125101	Structured	0.395525	Uncertain	0.873	0.261	0.000											-6.685	Likely Benign	0.350	Ambiguous	Likely Benign	0.10	Likely Benign	0.0	0.74	Ambiguous	0.42	Likely Benign	-0.10	Likely Benign	0.203	Likely Benign	-2.84	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.74	Pathogenic	0.13	Tolerated			0.1559	0.5476		3	2	0.0	14.03
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.2492A>T	E831V 2D AIThe SynGAP1 missense variant E831V is not reported in ClinVar and has no gnomAD allele. Prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts a benign effect, SGM‑Consensus indicates a likely pathogenic outcome, and Foldetta data are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.626927	Disordered	0.617732	Binding	0.319	0.874	0.375											-6.327	Likely Benign	0.629	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-3.43	Deleterious	0.891	Possibly Damaging	0.492	Possibly Damaging	2.32	Pathogenic	0.02	Affected			0.0604	0.7407		-2	-2	7.7	-29.98
c.2541G>C	Q847H 2D AIThe SynGAP1 missense variant Q847H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) and the SGM‑Consensus result point to a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-4.208	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-2.82	Deleterious	0.990	Probably Damaging	0.925	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.1429	0.3634		3	0	0.3	9.01
c.2541G>T	Q847H 2D AIThe SynGAP1 missense variant Q847H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions (seven pathogenic vs. three benign) and the SGM‑Consensus support a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-4.208	Likely Benign	0.720	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-2.82	Deleterious	0.990	Probably Damaging	0.925	Probably Damaging	2.27	Pathogenic	0.00	Affected			0.1429	0.3634		3	0	0.3	9.01
c.2803G>A	A935T 2D AIThe SynGAP1 missense variant A935T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625											-4.247	Likely Benign	0.228	Likely Benign	Likely Benign										0.204	Likely Benign	-1.27	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.33	Pathogenic	0.00	Affected			0.1670	0.6599		1	0	-2.5	30.03
c.2873A>C	H958P 2D AIThe SynGAP1 missense variant H958P is listed in ClinVar as a benign alteration (ClinVar ID 1006798.0) and is present in the gnomAD database (gnomAD ID 6‑33443425‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar benign status, showing no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.985964	Disordered	0.976011	Binding	0.371	0.913	0.750					Benign		1	6-33443425-A-C	2	1.24e-6	-8.369	Likely Pathogenic	0.068	Likely Benign	Likely Benign										0.204	Likely Benign	-0.36	Neutral	0.925	Possibly Damaging	0.316	Benign	4.14	Benign	0.10	Tolerated	3.77	5	0.2290	0.4701		0	-2	1.6	-40.02
c.3068C>T	S1023L 2D AIThe SynGAP1 missense variant S1023L is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the balance of evidence from the majority of tools and the SGM‑Consensus indicates a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.831250	Disordered	0.990262	Binding	0.322	0.750	0.500											-5.735	Likely Benign	0.705	Likely Pathogenic	Likely Benign										0.204	Likely Benign	-3.47	Deleterious	0.991	Probably Damaging	0.991	Probably Damaging	2.47	Pathogenic	0.01	Affected			0.1080	0.4923		-3	-2	4.6	26.08
c.313T>C	S105P 2D AIThe SynGAP1 missense variant S105P is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only two tools—polyPhen‑2 HumDiv and SIFT—predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.669201	Binding	0.364	0.870	0.625					Uncertain		1				-3.631	Likely Benign	0.166	Likely Benign	Likely Benign										0.204	Likely Benign	0.03	Neutral	0.808	Possibly Damaging	0.212	Benign	4.00	Benign	0.00	Affected	4.32	1	0.2236	0.4584		-1	1	-0.8	10.04
c.3464T>A	V1155E 2D AIThe SynGAP1 missense variant V1155E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments highlight a discrepancy: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus indicates likely benign; Foldetta stability analysis is unavailable. Consequently, the evidence is evenly split between benign and pathogenic interpretations, and no ClinVar entry contradicts these findings. The variant’s clinical significance remains uncertain, with no definitive leaning toward benign or pathogenic based on current predictions. 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											-3.175	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-2.01	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	2.58	Benign	0.02	Affected			0.0973	0.1727		-2	-2	-7.7	29.98
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.3644A>C	K1215T 2D AIThe SynGAP1 missense variant K1215T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect; this conclusion is not contradicted by any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.008	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.204	Likely Benign	-4.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.1972	0.2214		0	-1	3.2	-27.07
c.3685C>G	Q1229E 2D AIThe SynGAP1 missense change Q1229E lies in a coiled‑coil domain. ClinVar has no entry for this variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-7.319	In-Between	0.274	Likely Benign	Likely Benign										0.204	Likely Benign	-1.75	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.80	Pathogenic	0.17	Tolerated			0.1184	0.1336		2	2	0.0	0.98
c.3838A>C	M1280L 2D AIThe SynGAP1 missense variant M1280L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for M1280L, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-1.391	Likely Benign	0.092	Likely Benign	Likely Benign										0.204	Likely Benign	-2.23	Neutral	0.052	Benign	0.017	Benign	2.40	Pathogenic	0.00	Affected			0.1113	0.3186		4	2	1.9	-18.03
c.3838A>T	M1280L 2D AIThe SynGAP1 missense variant M1280L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar claim exists for this variant. Thus, based on current computational predictions, the M1280L variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-1.391	Likely Benign	0.092	Likely Benign	Likely Benign										0.204	Likely Benign	-2.23	Neutral	0.052	Benign	0.017	Benign	2.40	Pathogenic	0.00	Affected			0.1113	0.3186		4	2	1.9	-18.03
c.3887A>G	E1296G 2D AIThe SynGAP1 missense variant E1296G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.894444	Binding	0.530	0.809	0.625											-2.864	Likely Benign	0.221	Likely Benign	Likely Benign										0.204	Likely Benign	-5.10	Deleterious	0.992	Probably Damaging	0.868	Possibly Damaging	2.56	Benign	0.01	Affected			0.2971	0.5231		0	-2	3.1	-72.06
c.3913A>C	T1305P 2D AIThe SynGAP1 missense variant T1305P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.894658	Binding	0.390	0.873	0.875											-1.882	Likely Benign	0.058	Likely Benign	Likely Benign										0.204	Likely Benign	-1.41	Neutral	0.027	Benign	0.114	Benign	2.86	Benign	0.03	Affected			0.2157	0.5386		0	-1	-0.9	-3.99
c.985C>G	R329G 2D 3DClick to see structure in 3D Viewer AISynGAP1 R329G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls are made by FoldX, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments give an overall pathogenic signal: AlphaMissense‑Optimized is inconclusive, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta is inconclusive. Taken together, the majority of evidence points to a pathogenic effect, and 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	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-12.426	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous	2.21	Destabilizing	0.3	1.58	Ambiguous	1.90	Ambiguous	0.92	Ambiguous	0.204	Likely Benign	-4.78	Deleterious	0.653	Possibly Damaging	0.293	Benign	4.03	Benign	0.04	Affected			0.3147	0.3037		-3	-2	4.1	-99.14
c.1103C>A	P368Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P368Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Remaining tools (AlphaMissense‑Default, FoldX, Rosetta, Foldetta, premPS) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of definitive predictions (five pathogenic vs. three benign) indicate that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.363090	Structured	0.439989	Uncertain	0.580	0.677	0.250											-6.019	Likely Benign	0.413	Ambiguous	Likely Benign	1.56	Ambiguous	0.8	1.71	Ambiguous	1.64	Ambiguous	0.71	Ambiguous	0.205	Likely Benign	-5.10	Deleterious	0.991	Probably Damaging	0.881	Possibly Damaging	1.71	Pathogenic	0.04	Affected			0.1694	0.5283		0	-1	-1.9	31.01
c.1441C>A	H481N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H481N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools—Rosetta and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000											-8.229	Likely Pathogenic	0.381	Ambiguous	Likely Benign	0.16	Likely Benign	0.1	0.54	Ambiguous	0.35	Likely Benign	0.09	Likely Benign	0.205	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.68	Benign	0.57	Tolerated			0.1205	0.1631		2	1	-0.3	-23.04
c.1921T>C	S641P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and SIFT. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leaning toward benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. 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.		GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000											-6.907	Likely Benign	0.378	Ambiguous	Likely Benign	1.73	Ambiguous	1.3	0.07	Likely Benign	0.90	Ambiguous	0.59	Ambiguous	0.205	Likely Benign	-3.05	Deleterious	0.000	Benign	0.000	Benign	3.34	Benign	0.04	Affected			0.2289	0.5791		1	-1	-0.8	10.04
c.2773C>A	L925I 2D AIThe SynGAP1 missense variant L925I is not 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 predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of consensus tools (five pathogenic vs. three benign) lean toward a pathogenic interpretation. This prediction does not contradict 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.			0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-5.266	Likely Benign	0.828	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-1.38	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.37	Pathogenic	0.00	Affected			0.1192	0.3405		2	2	0.7	0.00
c.3059G>C	R1020P 2D AIThe SynGAP1 missense variant R1020P is listed in ClinVar (ID 3700393.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Pathogenic” (3 pathogenic vs. 1 benign votes). High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” SGM‑Consensus as “Likely Pathogenic,” and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500					Uncertain		1				-3.491	Likely Benign	0.902	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.50	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.46	Pathogenic	0.00	Affected			0.2077	0.5109		0	-2	2.9	-59.07
c.3257C>G	P1086R 2D AIThe SynGAP1 missense variant P1086R is not 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, 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, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy consensus is inconclusive. Therefore, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000											-5.190	Likely Benign	0.848	Likely Pathogenic	Ambiguous										0.205	Likely Benign	-3.42	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.86	Benign	0.00	Affected			0.1319	0.3551		0	-2	-2.9	59.07
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.532A>G	K178E 2D AIThe SynGAP1 missense variant K178E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-13.695	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.205	Likely Benign	-2.63	Deleterious	0.905	Possibly Damaging	0.393	Benign	3.90	Benign	0.01	Affected			0.4659	0.0952		0	1	0.4	0.94
c.563G>T	S188I 2D AIThe SynGAP1 missense variant S188I 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, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus also pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S188I, 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		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-12.133	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.205	Likely Benign	-3.98	Deleterious	0.995	Probably Damaging	0.880	Possibly Damaging	3.90	Benign	0.00	Affected			0.0878	0.6335		-1	-2	5.3	26.08
c.817G>A	E273K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E273K is not reported in ClinVar and is present in gnomAD (ID 6‑33437722‑G‑A). Functional prediction tools that agree on benign impact include REVEL, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, and SIFT. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions marked uncertain are FoldX and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools lean toward a benign 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	C2	0.071867	Structured	0.398918	Uncertain	0.863	0.196	0.125								6-33437722-G-A	1	6.20e-7	-12.690	Likely Pathogenic	0.917	Likely Pathogenic	Ambiguous	-0.57	Ambiguous	0.3	-0.38	Likely Benign	-0.48	Likely Benign	0.23	Likely Benign	0.205	Likely Benign	-2.66	Deleterious	0.896	Possibly Damaging	0.415	Benign	1.77	Pathogenic	0.12	Tolerated	3.38	18	0.2312	0.2996		1	0	-0.4	-0.94
c.826C>T	P276S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P276S missense change is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic calls from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Four tools predict benign while five predict pathogenic, and four additional methods (FoldX, Rosetta, Foldetta, premPS) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—yields a tie and is therefore inconclusive; Foldetta also reports an uncertain stability change. Taken together, the preponderance of evidence leans toward a pathogenic effect, and this assessment does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.037156	Structured	0.338937	Uncertain	0.724	0.230	0.250											-5.946	Likely Benign	0.142	Likely Benign	Likely Benign	1.78	Ambiguous	0.2	0.96	Ambiguous	1.37	Ambiguous	0.65	Ambiguous	0.205	Likely Benign	-3.25	Deleterious	0.835	Possibly Damaging	0.468	Possibly Damaging	1.92	Pathogenic	0.05	Affected			0.3191	0.3736		1	-1	0.8	-10.04
c.1221G>C	Q407H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407H (C2 domain) has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is uncertain. No evidence from FoldX, Rosetta, or Foldetta supports a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000											-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	0.206	Likely Benign	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0.1205	0.3154		0	3	0.3	9.01
c.1221G>T	Q407H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q407H is listed in ClinVar with an uncertain significance (ClinVar ID 2772184.0) 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 premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked as uncertain include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. 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 as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Q407H. This conclusion does not conflict with the ClinVar designation of uncertain significance, which remains unresolved pending further evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000					Uncertain		1				-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	0.206	Likely Benign	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0.1205	0.3154		0	3	0.3	9.01
c.1339G>T	V447F 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant V447F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports an uncertain effect on protein folding. Overall, the majority of predictions lean toward pathogenicity, suggesting the variant is most likely pathogenic, a conclusion that does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.250310	Structured	0.283801	Uncertain	0.970	0.243	0.000					Uncertain		1				-8.673	Likely Pathogenic	0.701	Likely Pathogenic	Likely Benign	1.40	Ambiguous	0.3	0.61	Ambiguous	1.01	Ambiguous	0.20	Likely Benign	0.206	Likely Benign	-2.62	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.44	Benign	0.03	Affected			0.0551	0.3055		-1	-1	-1.4	48.04
c.1609G>T	A537S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537S is reported in gnomAD (6-33438852-G-T) and has no ClinVar entry. Consensus from multiple in silico predictors indicates a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all score benign, while polyPhen‑2 (HumDiv and HumVar) and FATHMM predict pathogenicity. When predictions are grouped, the majority of tools (ten) support benign, whereas three tools support pathogenic. High‑accuracy assessments further reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Consequently, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000								6-33438852-G-T	1	6.20e-7	-3.602	Likely Benign	0.095	Likely Benign	Likely Benign	0.28	Likely Benign	0.0	0.46	Likely Benign	0.37	Likely Benign	0.28	Likely Benign	0.206	Likely Benign	-0.66	Neutral	0.528	Possibly Damaging	0.592	Possibly Damaging	-1.25	Pathogenic	0.60	Tolerated	3.37	35	0.2729	0.4431		1	1	-2.6	16.00
c.2306T>G	L769R 2D AIThe SynGAP1 missense variant L769R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-6.245	Likely Benign	0.493	Ambiguous	Likely Benign										0.206	Likely Benign	-1.66	Neutral	0.003	Benign	0.006	Benign	3.91	Benign	0.00	Affected			0.1286	0.0702		-3	-2	-8.3	43.03
c.2348T>A	M783K 2D AIThe SynGAP1 missense variant M783K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while 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 toward a benign impact. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-4.923	Likely Benign	0.693	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-2.70	Deleterious	0.925	Possibly Damaging	0.424	Benign	2.66	Benign	0.01	Affected			0.1730	0.0912		0	-1	-5.8	-3.02
c.2351C>A	A784D 2D AIThe SynGAP1 missense variant A784D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.801317	Disordered	0.708872	Binding	0.314	0.896	0.625											-3.784	Likely Benign	0.766	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-1.21	Neutral	0.411	Benign	0.237	Benign	2.68	Benign	0.16	Tolerated			0.1824	0.2193		0	-2	-5.3	44.01
c.2538A>C	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta (FoldX‑MD/Rosetta) stability assessment is available. Overall, the preponderance of evidence from multiple high‑accuracy predictors indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.2538A>T	L846F 2D AIThe SynGAP1 missense variant L846F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic or deleterious impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. AlphaMissense‑Optimized is uncertain, providing no definitive direction. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-10.559	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous										0.206	Likely Benign	-2.88	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.0665	0.2912		2	0	-1.0	34.02
c.3256C>G	P1086A 2D AIThe SynGAP1 missense variant P1086A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors benign, and Foldetta data are unavailable. Taken together, the balance of evidence points to a benign effect for P1086A. This conclusion does not conflict with the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000											-4.317	Likely Benign	0.372	Ambiguous	Likely Benign										0.206	Likely Benign	-2.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.78	Benign	0.00	Affected			0.3084	0.4463		1	-1	3.4	-26.04
c.3425C>T	S1142F 2D AIThe SynGAP1 missense variant S1142F has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority, and Foldetta data are unavailable. Overall, the balance of evidence—especially from the high‑accuracy tools—suggests that the variant is most likely benign. 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.			0.919029	Disordered	0.719935	Binding	0.276	0.844	1.000											-5.074	Likely Benign	0.508	Ambiguous	Likely Benign										0.206	Likely Benign	-3.70	Deleterious	0.918	Possibly Damaging	0.827	Possibly Damaging	2.65	Benign	0.00	Affected			0.0861	0.5603		-3	-2	3.6	60.10
c.3740G>C	R1247T 2D AIThe SynGAP1 missense variant R1247T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score, which is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic. No Foldetta stability result is available. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.302	Likely Benign	0.598	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-4.79	Deleterious	0.980	Probably Damaging	0.783	Possibly Damaging	1.71	Pathogenic	0.00	Affected			0.1543	0.2403		-1	-1	3.8	-55.08
c.3745A>G	R1249G 2D AIThe SynGAP1 missense variant R1249G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain and SGM‑Consensus is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-7.405	In-Between	0.684	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-5.38	Deleterious	0.990	Probably Damaging	0.828	Possibly Damaging	1.70	Pathogenic	0.00	Affected			0.3087	0.2393		-3	-2	4.1	-99.14
c.3772C>G	Q1258E 2D AIThe SynGAP1 missense variant Q1258E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3/4 pathogenic votes). High‑accuracy assessments further support this: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus remains pathogenic; Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a pathogenic impact, which is consistent with the lack of ClinVar annotation and gnomAD absence. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-9.894	Likely Pathogenic	0.666	Likely Pathogenic	Likely Benign										0.206	Likely Benign	-2.39	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.01	Pathogenic	0.00	Affected			0.0958	0.1897		2	2	0.0	0.98
c.2018T>C	L673P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673P is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. All other evaluated tools—SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts Pathogenic. Taken together, the overwhelming majority of predictions, including the high‑accuracy tools, classify the variant as pathogenic. 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	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-12.160	Likely Pathogenic	0.622	Likely Pathogenic	Likely Benign	2.41	Destabilizing	0.3	1.63	Ambiguous	2.02	Destabilizing	1.17	Destabilizing	0.207	Likely Benign	-4.10	Deleterious	1.000	Probably Damaging	0.978	Probably Damaging	3.37	Benign	0.02	Affected			0.3552	0.1474		-3	-3	-5.4	-16.04
c.2252C>T	P751L 2D AIThe SynGAP1 missense variant P751L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.667683	Binding	0.386	0.866	0.625											-3.558	Likely Benign	0.143	Likely Benign	Likely Benign										0.207	Likely Benign	-1.62	Neutral	0.316	Benign	0.062	Benign	2.94	Benign	0.24	Tolerated			0.2318	0.6451		-3	-3	5.4	16.04
c.2612A>C	H871P 2D AIThe SynGAP1 missense variant H871P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.679301	Binding	0.279	0.858	0.250											-3.420	Likely Benign	0.074	Likely Benign	Likely Benign										0.207	Likely Benign	-0.91	Neutral	0.510	Possibly Damaging	0.206	Benign	2.63	Benign	0.18	Tolerated			0.2163	0.3757		0	-2	1.6	-40.02
c.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.3391C>G	P1131A 2D AIThe SynGAP1 missense variant P1131A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT 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 further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.855155	Binding	0.360	0.899	0.750											-4.785	Likely Benign	0.171	Likely Benign	Likely Benign										0.207	Likely Benign	-2.88	Deleterious	0.009	Benign	0.008	Benign	5.36	Benign	0.00	Affected			0.2977	0.5501		1	-1	3.4	-26.04
c.3760G>C	E1254Q 2D AIThe SynGAP1 missense variant E1254Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—favors pathogenic (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 tools points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.657645	Disordered	0.403242	Uncertain	0.886	0.555	0.625											-9.041	Likely Pathogenic	0.511	Ambiguous	Likely Benign										0.207	Likely Benign	-2.18	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.35	Pathogenic	0.03	Affected			0.0768	0.5258		2	2	0.0	-0.98
c.3814G>C	E1272Q 2D AIThe SynGAP1 E1272Q missense variant is catalogued in gnomAD (variant ID 6‑33447862‑G‑C) but has no ClinVar entry. Prediction tools cluster into two groups: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, a majority‑vote aggregator of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the preponderance of evidence (seven pathogenic versus three benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.766082	Binding	0.799	0.677	0.500								6-33447862-G-C	1	6.45e-7	-3.000	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.207	Likely Benign	-2.53	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.25	Pathogenic	0.00	Affected	3.77	5	0.0746	0.5258		2	2	0.0	-0.98
c.1069C>G	H357D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H357D missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta also predicts a benign outcome. No prediction or folding‑stability result is missing or inconclusive. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.203355	Structured	0.399052	Uncertain	0.861	0.413	0.250											-12.013	Likely Pathogenic	0.559	Ambiguous	Likely Benign	-0.23	Likely Benign	0.4	-0.27	Likely Benign	-0.25	Likely Benign	0.48	Likely Benign	0.208	Likely Benign	-1.90	Neutral	0.495	Possibly Damaging	0.169	Benign	4.22	Benign	0.08	Tolerated			0.2782	0.1976		1	-1	-0.3	-22.05
c.1112G>A	S371N 2D AIThe SynGAP1 missense variant S371N is not reported in ClinVar and is absent from gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments are consistent: AlphaMissense‑Optimized classifies the variant as benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375											-5.950	Likely Benign	0.160	Likely Benign	Likely Benign	0.21	Likely Benign	0.8	-0.59	Ambiguous	-0.19	Likely Benign	0.25	Likely Benign	0.208	Likely Benign	-0.31	Neutral	0.666	Possibly Damaging	0.067	Benign	4.64	Benign	0.27	Tolerated			0.2068	0.5100		1	1	-2.7	27.03
c.1264G>C	E422Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E422Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, and FATHMM, while those that predict a pathogenic effect are SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool rates the variant as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.067594	Structured	0.426709	Uncertain	0.965	0.255	0.000											-9.460	Likely Pathogenic	0.926	Likely Pathogenic	Ambiguous	0.32	Likely Benign	0.0	0.21	Likely Benign	0.27	Likely Benign	-0.15	Likely Benign	0.208	Likely Benign	-2.26	Neutral	0.997	Probably Damaging	0.973	Probably Damaging	3.38	Benign	0.03	Affected			0.1045	0.4913		2	2	0.0	-0.98
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.172A>C	M58L 2D AIThe SynGAP1 missense variant M58L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. Only SIFT predicts a deleterious impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus result is benign; Foldetta data are not available. Consequently, the aggregate evidence points to a benign effect for M58L, 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		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000											-0.661	Likely Benign	0.240	Likely Benign	Likely Benign										0.208	Likely Benign	-0.11	Neutral	0.006	Benign	0.039	Benign	4.77	Benign	0.00	Affected			0.1514	0.4621		4	2	1.9	-18.03
c.172A>T	M58L 2D AIThe SynGAP1 missense variant M58L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.188120	Structured	0.484415	Uncertain	0.515	0.665	0.000											-0.661	Likely Benign	0.240	Likely Benign	Likely Benign										0.208	Likely Benign	-0.11	Neutral	0.006	Benign	0.039	Benign	4.77	Benign	0.00	Affected			0.1514	0.4621		4	2	1.9	-18.03
c.2348T>G	M783R 2D AIThe SynGAP1 missense variant M783R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.738119	Binding	0.331	0.889	0.625											-3.849	Likely Benign	0.655	Likely Pathogenic	Likely Benign										0.208	Likely Benign	-2.69	Deleterious	0.925	Possibly Damaging	0.529	Possibly Damaging	2.66	Benign	0.01	Affected			0.1815	0.0893		0	-1	-6.4	24.99
c.296A>T	E99V 2D AIThe SynGAP1 missense variant E99V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus likewise reports Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for E99V, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.645246	Binding	0.325	0.874	0.500											-3.628	Likely Benign	0.544	Ambiguous	Likely Benign										0.208	Likely Benign	-1.69	Neutral	0.000	Benign	0.000	Benign	4.02	Benign	0.00	Affected			0.1109	0.8175		-2	-2	7.7	-29.98
c.3158G>A	S1053N 2D AIThe SynGAP1 missense variant S1053N is reported in gnomAD (variant ID 6‑33443710‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus also indicates a likely benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875								6-33443710-G-A	1	6.21e-7	-6.282	Likely Benign	0.120	Likely Benign	Likely Benign										0.208	Likely Benign	-0.54	Neutral	0.625	Possibly Damaging	0.193	Benign	5.30	Benign	0.34	Tolerated	3.77	5	0.1953	0.4605		1	1	-2.7	27.03
c.3409C>A	H1137N 2D AIThe SynGAP1 missense variant H1137N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.756488	Binding	0.314	0.879	0.875											-3.105	Likely Benign	0.063	Likely Benign	Likely Benign										0.208	Likely Benign	-1.53	Neutral	0.625	Possibly Damaging	0.353	Benign	5.34	Benign	0.00	Affected			0.1983	0.3638		2	1	-0.3	-23.04
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.371C>A	A124E 2D AIThe SynGAP1 missense variant A124E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A124E, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.699139	Binding	0.340	0.883	0.750											-3.444	Likely Benign	0.667	Likely Pathogenic	Likely Benign										0.208	Likely Benign	-1.21	Neutral	0.993	Probably Damaging	0.733	Possibly Damaging	4.11	Benign	0.01	Affected			0.1498	0.2233		0	-1	-5.3	58.04
c.3751C>A	Q1251K 2D AIThe SynGAP1 missense variant Q1251K is catalogued in gnomAD (ID 6‑33446743‑C‑A) but has no ClinVar entry. Functional prediction tools show a split: benign calls from REVEL and FATHMM, whereas the majority—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—label it pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports it as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as Uncertain, SGM‑Consensus remains Likely Pathogenic, and Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875								6-33446743-C-A	1	6.20e-7	-11.113	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous										0.208	Likely Benign	-2.92	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.53	Benign	0.00	Affected	3.77	5	0.1418	0.2635		1	1	-0.4	0.04
c.3956C>A	A1319D 2D AIThe SynGAP1 missense variant A1319D is reported in gnomAD (ID 6‑33451830‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the same four tools) is benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for A1319D, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.960481	Binding	0.454	0.851	0.750								6-33451830-C-A			-5.156	Likely Benign	0.297	Likely Benign	Likely Benign										0.208	Likely Benign	-0.85	Neutral	0.971	Probably Damaging	0.813	Possibly Damaging	4.08	Benign	0.01	Affected	3.77	5	0.2290	0.2702		-2	0	-5.3	44.01
c.577G>A	A193T 2D AIThe SynGAP1 missense variant A193T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-4.973	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.208	Likely Benign	-1.36	Neutral	0.990	Probably Damaging	0.815	Possibly Damaging	4.07	Benign	0.21	Tolerated			0.1452	0.7231		1	0	-2.5	30.03
c.979C>G	L327V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L327V is reported in gnomAD (ID 6‑33437884‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.335645	Structured	0.409189	Uncertain	0.939	0.490	0.000								6-33437884-C-G	3	1.86e-6	-8.978	Likely Pathogenic	0.148	Likely Benign	Likely Benign	1.38	Ambiguous	0.1	0.67	Ambiguous	1.03	Ambiguous	1.31	Destabilizing	0.208	Likely Benign	-1.87	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.66	Benign	0.13	Tolerated	3.38	23	0.1648	0.4206		1	2	0.4	-14.03
c.1429A>G	M477V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477V is listed in ClinVar with no submitted interpretation and is present in the gnomAD database (variant ID 6‑33438461‑A‑G). Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen2_HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict benign or likely benign. Only two tools predict a pathogenic outcome: polyPhen2_HumDiv and FATHMM. Predictions from FoldX and Foldetta are uncertain. High‑accuracy methods reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, while Foldetta remains inconclusive. Taken together, the majority of evidence supports a benign classification for M477V, and this assessment does not contradict the ClinVar status, which currently has no pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000								6-33438461-A-G	1	6.20e-7	-3.995	Likely Benign	0.127	Likely Benign	Likely Benign	1.64	Ambiguous	0.3	0.42	Likely Benign	1.03	Ambiguous	0.24	Likely Benign	0.209	Likely Benign	-1.04	Neutral	0.716	Possibly Damaging	0.204	Benign	-1.19	Pathogenic	0.22	Tolerated	3.37	34	0.3093	0.3445		1	2	2.3	-32.06																10.1016/j.ajhg.2020.11.011
c.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.1910C>A	S637Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the majority of individual predictors (seven versus five) lean toward pathogenicity, and the consensus‑based SGM‑Consensus also supports a likely pathogenic classification. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-12.633	Likely Pathogenic	0.770	Likely Pathogenic	Likely Benign	0.13	Likely Benign	0.1	1.52	Ambiguous	0.83	Ambiguous	0.50	Likely Benign	0.209	Likely Benign	-3.78	Deleterious	0.985	Probably Damaging	0.681	Possibly Damaging	3.35	Benign	0.00	Affected			0.0968	0.4071		-3	-2	-0.5	76.10
c.2080G>C	A694P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, while the majority of other in silico predictors (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; premPS is uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as Likely Pathogenic, with three of four votes pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for A694P. This conclusion is consistent with the absence of ClinVar annotation and gnomAD data, and there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000											-10.569	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.39	Destabilizing	0.2	5.59	Destabilizing	4.49	Destabilizing	0.82	Ambiguous	0.209	Likely Benign	-2.77	Deleterious	0.988	Probably Damaging	0.578	Possibly Damaging	3.44	Benign	0.03	Affected			0.2265	0.3829		1	-1	-3.4	26.04
c.2129A>G	K710R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K710R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments—all of which are available—show benign predictions: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-6.295	Likely Benign	0.141	Likely Benign	Likely Benign	0.04	Likely Benign	0.0	-0.14	Likely Benign	-0.05	Likely Benign	0.29	Likely Benign	0.209	Likely Benign	-2.78	Deleterious	0.983	Probably Damaging	0.962	Probably Damaging	3.44	Benign	0.02	Affected			0.3351	0.0789		3	2	-0.6	28.01
c.2529G>A	M843I 2D AIThe SynGAP1 missense variant M843I is catalogued in gnomAD (6‑33443081‑G‑A) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus score (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 as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is 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 an equal number of benign and pathogenic calls; however, the majority of conventional tools lean toward benign, and the high‑accuracy consensus also favors benign. Thus, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375								6-33443081-G-A	1	6.20e-7	-6.219	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.97	Neutral	0.925	Possibly Damaging	0.954	Probably Damaging	2.66	Benign	0.03	Affected	3.77	5	0.1497	0.3630		1	2	2.6	-18.03
c.2529G>C	M843I 2D AIThe SynGAP1 missense variant M843I is not reported 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 (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, 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 lean toward pathogenicity, 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		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-6.219	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.97	Neutral	0.925	Possibly Damaging	0.954	Probably Damaging	2.66	Benign	0.03	Affected	3.77	5	0.1497	0.3630		1	2	2.6	-18.03
c.2529G>T	M843I 2D AIThe SynGAP1 missense variant M843I is not reported 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 (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, 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 lean toward pathogenicity, 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		0.585406	Disordered	0.617934	Binding	0.327	0.854	0.375											-6.219	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.97	Neutral	0.925	Possibly Damaging	0.954	Probably Damaging	2.66	Benign	0.03	Affected	3.77	5	0.1497	0.3630		1	2	2.6	-18.03
c.2729G>C	G910A 2D AIThe SynGAP1 missense variant G910A is listed in ClinVar with an “Uncertain” status (ClinVar ID 2091237.0) and is present in gnomAD (6‑33443281‑G‑C). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. The remaining predictions are uncertain: AlphaMissense‑Default is inconclusive, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.707319	Binding	0.264	0.917	0.250					Uncertain		1	6-33443281-G-C	1	6.20e-7	-3.587	Likely Benign	0.361	Ambiguous	Likely Benign										0.209	Likely Benign	-1.43	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	2.78	Benign	0.10	Tolerated	3.77	5	0.3753	0.4544		1	0	2.2	14.03
c.3023A>C	D1008A 2D AIThe SynGAP1 D1008A variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625											-3.210	Likely Benign	0.861	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-2.65	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.69	Benign	0.03	Affected			0.4014	0.6444		0	-2	5.3	-44.01
c.3047A>G	D1016G 2D AIThe SynGAP1 missense variant D1016G has no ClinVar entry and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support this split: AlphaMissense‑Optimized indicates a benign effect, whereas the SGM‑Consensus classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.801317	Disordered	0.944705	Binding	0.323	0.811	0.625											-1.918	Likely Benign	0.621	Likely Pathogenic	Likely Benign										0.209	Likely Benign	-3.40	Deleterious	0.924	Possibly Damaging	0.652	Possibly Damaging	2.46	Pathogenic	0.01	Affected			0.3624	0.7059		1	-1	3.1	-58.04
c.3262A>C	S1088R 2D AIThe SynGAP1 missense variant S1088R is not reported in ClinVar and has no gnomAD entry. 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Benign, reflecting the majority of benign calls. High‑accuracy assessments further support this: AlphaMissense‑Optimized labels the variant as Pathogenic, but the SGM‑Consensus (majority vote) remains 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 leans toward a benign effect; this conclusion does not conflict with ClinVar, which contains no entry for S1088R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-4.588	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.72	Benign	0.01	Affected	3.77	5	0.1190	0.4502		-1	0	-3.7	69.11
c.3383G>C	G1128A 2D AIThe SynGAP1 missense variant G1128A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.865136	Binding	0.309	0.911	0.875											-5.015	Likely Benign	0.081	Likely Benign	Likely Benign										0.209	Likely Benign	-0.26	Neutral	0.009	Benign	0.008	Benign	4.47	Benign	0.46	Tolerated			0.3588	0.5252		1	0	2.2	14.03
c.3391C>T	P1131S 2D AIThe SynGAP1 missense variant P1131S is reported in gnomAD (variant ID 6‑33443943‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this is not contradictory to ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.855155	Binding	0.360	0.899	0.750								6-33443943-C-T	1	6.72e-7	-4.089	Likely Benign	0.246	Likely Benign	Likely Benign										0.209	Likely Benign	-2.62	Deleterious	0.025	Benign	0.015	Benign	5.54	Benign	0.00	Affected	4.32	4	0.2936	0.5936		-1	1	0.8	-10.04
c.3404A>G	K1135R 2D AIThe SynGAP1 missense variant K1135R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign impact for K1135R, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875											-2.286	Likely Benign	0.122	Likely Benign	Likely Benign										0.209	Likely Benign	-0.82	Neutral	0.586	Possibly Damaging	0.321	Benign	5.44	Benign	0.15	Tolerated			0.5095	0.1674	Weaken	3	2	-0.6	28.01
c.3406C>G	Q1136E 2D AIThe SynGAP1 missense variant Q1136E is catalogued in gnomAD (ID 6‑33443958‑C‑G) and has no ClinVar entry. All evaluated in silico predictors uniformly classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely pathogenic outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the computational evidence strongly supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.775584	Binding	0.321	0.884	0.875								6-33443958-C-G	4	2.71e-6	-6.677	Likely Benign	0.277	Likely Benign	Likely Benign										0.209	Likely Benign	-1.13	Neutral	0.022	Benign	0.026	Benign	5.46	Benign	0.11	Tolerated	4.32	2	0.1487	0.2886		2	2	0.0	0.98
c.3464T>G	V1155G 2D AIThe SynGAP1 missense variant V1155G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give mixed results: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (benign), FATHMM (benign), and PROVEAN (benign), reports a benign outcome; Foldetta’s stability assessment is unavailable. Overall, the majority of conventional tools lean toward pathogenicity, whereas the high‑accuracy consensus leans benign, leaving the functional impact uncertain. The variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.750527	Disordered	0.855718	Binding	0.335	0.857	0.500											-3.018	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic										0.209	Likely Benign	-1.91	Neutral	0.997	Probably Damaging	0.999	Probably Damaging	2.59	Benign	0.05	Affected			0.2211	0.2374		-1	-3	-4.6	-42.08
c.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.3741G>C	R1247S 2D AIThe SynGAP1 missense variant R1247S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1247S. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.935	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-4.79	Deleterious	0.961	Probably Damaging	0.721	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2802	0.1977		0	-1	3.7	-69.11
c.3741G>T	R1247S 2D AIThe SynGAP1 missense variant R1247S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” and Foldetta data are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for R1247S. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625											-6.935	Likely Benign	0.851	Likely Pathogenic	Ambiguous										0.209	Likely Benign	-4.79	Deleterious	0.961	Probably Damaging	0.721	Possibly Damaging	1.72	Pathogenic	0.00	Affected			0.2802	0.1977		0	-1	3.7	-69.11
c.3745A>T	R1249W 2D AIThe SynGAP1 missense variant R1249W is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) is pathogenic, and no Foldetta stability data are available. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus designation and contradicts the benign predictions from a minority of tools. Thus, the variant is most likely pathogenic, and this conclusion aligns with the lack of ClinVar annotation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-9.841	Likely Pathogenic	0.477	Ambiguous	Likely Benign										0.209	Likely Benign	-6.18	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	1.68	Pathogenic	0.00	Affected			0.1256	0.2179		2	-3	3.6	30.03
c.3928A>C	T1310P 2D AIThe SynGAP1 missense variant T1310P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are unavailable, so no additional stability evidence is present. Overall, the consensus of available predictions indicates that T1310P is most likely benign, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.959076	Binding	0.398	0.904	0.750											-1.807	Likely Benign	0.058	Likely Benign	Likely Benign										0.209	Likely Benign	-1.48	Neutral	0.594	Possibly Damaging	0.298	Benign	2.75	Benign	0.04	Affected			0.1667	0.3604		0	-1	-0.9	-3.99
c.85A>G	M29V 2D AIThe SynGAP1 missense variant M29V is reported in gnomAD (ID 6‑33423494‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, representing the sole discordant signal. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for M29V, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250								6-33423494-A-G	1	6.20e-7	-1.841	Likely Benign	0.057	Likely Benign	Likely Benign										0.209	Likely Benign	-0.39	Neutral	0.006	Benign	0.091	Benign	4.27	Benign	0.00	Affected	4.32	1	0.4022	0.4433		1	2	2.3	-32.06
c.886T>G	S296A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S296A (ClinVar ID 469166.0) is listed as ClinVar status Uncertain and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign or neutral. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic ones. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a benign effect. No evidence from the available tools suggests a deleterious impact. Therefore, the variant is most likely benign, and this conclusion is consistent with its ClinVar status of Uncertain rather than pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.282669	Uncertain	0.887	0.284	0.250					Uncertain		1				-6.847	Likely Benign	0.247	Likely Benign	Likely Benign	0.50	Ambiguous	0.3	-0.26	Likely Benign	0.12	Likely Benign	0.35	Likely Benign	0.209	Likely Benign	-1.79	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.97	Pathogenic	0.65	Tolerated	3.40	16	0.4958	0.5522		1	1	2.6	-16.00	182.5	26.6	-0.2	0.1	-0.5	0.0		X						Potentially Pathogenic	The hydroxyl group of the Ser296 side chain, located in an anti-parallel β sheet strand (res. Met289-Pro298), stably hydrogen bonds with the carboxylate group of Asp330 in a neighboring β strand (res. Ala322-Asp332). The backbone carbonyl group of Ser296 also hydrogen bonds with the guanidinium group of Arg279 in another nearby β strand (res. Arg279-Cys285). In the variant simulations, the methyl group of the Ala296 side chain cannot hydrogen bond with Asp330, causing the carboxylate group positioning to fluctuate more than in the WT simulations.Although the residue swap does not seem to affect the anti-parallel β sheet assembly during the simulations, it is possible that the Ser296-Asp330 hydrogen bond plays a crucial role in maintaining the C2 domain fold. Notably, because Ser296 is located near the membrane interface, the potential effect of the residue swap on the SynGAP-membrane association cannot be addressed by solvent-only simulations.
c.892C>A	P298T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P298T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar) and FATHMM. The remaining tools—FoldX, Rosetta, Foldetta, and ESM1b—return uncertain results and are treated as unavailable for pathogenicity inference. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the preponderance of evidence points to a benign effect for P298T, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500											-7.366	In-Between	0.104	Likely Benign	Likely Benign	1.44	Ambiguous	0.2	1.03	Ambiguous	1.24	Ambiguous	0.04	Likely Benign	0.209	Likely Benign	-0.13	Neutral	0.939	Possibly Damaging	0.739	Possibly Damaging	1.96	Pathogenic	1.00	Tolerated			0.1595	0.6349		0	-1	0.9	3.99
c.92G>C	R31P 2D AIThe SynGAP1 missense variant R31P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign impact for R31P, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.437905	Uncertain	0.324	0.878	0.250											-3.185	Likely Benign	0.300	Likely Benign	Likely Benign										0.209	Likely Benign	-1.64	Neutral	0.841	Possibly Damaging	0.809	Possibly Damaging	3.96	Benign	0.00	Affected			0.2220	0.5005		0	-2	2.9	-59.07
c.1609G>A	A537T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537T is catalogued in gnomAD (6‑33438852‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign; the SGM‑Consensus (majority vote) is Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts Benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000								6-33438852-G-A	2	1.24e-6	-4.704	Likely Benign	0.097	Likely Benign	Likely Benign	0.35	Likely Benign	0.0	0.29	Likely Benign	0.32	Likely Benign	0.37	Likely Benign	0.210	Likely Benign	-1.41	Neutral	0.953	Possibly Damaging	0.602	Possibly Damaging	-1.27	Pathogenic	0.44	Tolerated	3.37	35	0.1520	0.5440		0	1	-2.5	30.03
c.1994A>G	Y665C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665C is listed in ClinVar with no assertion (status: None) and is present in gnomAD (ID 6‑33441253‑A‑G). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also unavailable. Overall, the evidence is mixed, but the majority of high‑confidence tools lean toward a benign interpretation. Thus, the variant is most likely benign based on current predictions, and this does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000								6-33441253-A-G	1	6.20e-7	-9.007	Likely Pathogenic	0.261	Likely Benign	Likely Benign	1.05	Ambiguous	0.1	1.60	Ambiguous	1.33	Ambiguous	1.12	Destabilizing	0.210	Likely Benign	-3.22	Deleterious	1.000	Probably Damaging	0.981	Probably Damaging	3.45	Benign	0.14	Tolerated	3.38	28	0.2562	0.2019		-2	0	3.8	-60.04
c.19T>C	S7P 2D AIThe SynGAP1 missense variant S7P is reported in gnomAD (ID 6‑33420283‑T‑C) but has no ClinVar entry. In silico prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is benign; Foldetta results are unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign effect. This prediction is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.548467	Binding	0.386	0.922	0.750								6-33420283-T-C			-3.798	Likely Benign	0.111	Likely Benign	Likely Benign										0.210	Likely Benign	-0.23	Neutral	0.267	Benign	0.029	Benign	4.07	Benign	0.00	Affected	4.32	1	0.2474	0.4925		-1	1	-0.8	10.04
c.2006A>G	N669S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N669S is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33441265‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta (combining FoldX‑MD and Rosetta) is also inconclusive. No folding‑stability metrics (FoldX, Rosetta, Foldetta) provide definitive evidence. Overall, the majority of predictions lean toward a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. 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.		GAP	0.142424	Structured	0.086615	Uncertain	0.872	0.380	0.000								6-33441265-A-G	3	1.86e-6	-8.369	Likely Pathogenic	0.187	Likely Benign	Likely Benign	0.55	Ambiguous	0.1	1.88	Ambiguous	1.22	Ambiguous	0.35	Likely Benign	0.210	Likely Benign	-4.02	Deleterious	0.999	Probably Damaging	0.960	Probably Damaging	3.52	Benign	0.14	Tolerated	3.39	27	0.3521	0.4480		1	1	2.7	-27.03
c.2147G>A	R716Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R716Q is listed in ClinVar with an uncertain significance (ClinVar ID 411585.0) and is present in gnomAD (ID 6‑33441612‑G‑A). Functional prediction tools that report a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b, while premPS is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the balance of evidence leans toward a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000					Conflicting		2	6-33441612-G-A	4	2.48e-6	-8.338	Likely Pathogenic	0.308	Likely Benign	Likely Benign	-0.01	Likely Benign	0.0	0.47	Likely Benign	0.23	Likely Benign	0.58	Ambiguous	0.210	Likely Benign	-3.14	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.35	Benign	0.02	Affected	3.50	9	0.2834	0.2180		1	1	1.0	-28.06	250.0	48.9	0.0	0.0	-0.5	0.0						X		Uncertain	The guanidinium group of Arg716, located on the outer surface of an α-helix (res. Leu714-Arg726), forms a salt bridge with the carboxylate group of Asp720. In the variant simulations, the carboxamide group of Gln716 also forms a hydrogen bond with the carboxylate group of Asp720, although this bond is weaker than the Arg716 salt bridge in the WT. Overall, no adverse effects on the protein structure are observed in the simulations. However, because the model ends abruptly at the C-terminus, no definite conclusions can be drawn based on the simulations.
c.2440G>C	A814P 2D AIThe SynGAP1 missense variant A814P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors points to a benign effect for A814P, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.814830	Binding	0.368	0.902	0.250											-5.247	Likely Benign	0.351	Ambiguous	Likely Benign										0.210	Likely Benign	-1.88	Neutral	0.984	Probably Damaging	0.855	Possibly Damaging	2.64	Benign	0.05	Affected			0.1845	0.4941		1	-1	-3.4	26.04
c.2799C>G	H933Q 2D AIThe SynGAP1 H933Q 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, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction between the predictions and ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-3.042	Likely Benign	0.410	Ambiguous	Likely Benign										0.210	Likely Benign	-2.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.54	Benign	0.53	Tolerated			0.1654	0.3938		3	0	-0.3	-9.01
c.2882A>C	H961P 2D AIThe SynGAP1 missense variant H961P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, while only SIFT and ESM1b predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign verdict (3 benign vs. 1 pathogenic). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Consequently, the collective evidence indicates that H961P is most likely benign, and this conclusion is not in conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750											-8.434	Likely Pathogenic	0.071	Likely Benign	Likely Benign										0.210	Likely Benign	-0.58	Neutral	0.000	Benign	0.000	Benign	4.15	Benign	0.02	Affected			0.2061	0.4701		0	-2	1.6	-40.02
c.3334G>A	E1112K 2D AIThe SynGAP1 missense variant E1112K is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only two tools predict pathogenicity: SIFT and AlphaMissense‑Default. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the majority of predictions, including the high‑accuracy tools, suggest the variant is most likely benign, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.909381	Binding	0.335	0.902	0.875											-3.772	Likely Benign	0.684	Likely Pathogenic	Likely Benign										0.210	Likely Benign	0.15	Neutral	0.245	Benign	0.096	Benign	2.82	Benign	0.02	Affected			0.3002	0.7704		0	1	-0.4	-0.94
c.3404A>C	K1135T 2D AIThe SynGAP1 missense variant K1135T is listed in ClinVar (ID 1166087.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443956‑A‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. 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					Conflicting		2	6-33443956-A-C	1	6.75e-7	-4.778	Likely Benign	0.779	Likely Pathogenic	Likely Benign										0.210	Likely Benign	-0.90	Neutral	0.411	Benign	0.321	Benign	5.46	Benign	0.10	Tolerated	4.32	2	0.2544	0.3521		0	-1	3.2	-27.07
c.3531G>C	E1177D 2D AIThe SynGAP1 missense variant E1177D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Taken together, the majority of evidence indicates that E1177D is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.566503	Binding	0.542	0.705	0.250											-4.195	Likely Benign	0.162	Likely Benign	Likely Benign										0.210	Likely Benign	-0.74	Neutral	0.029	Benign	0.026	Benign	5.42	Benign	0.05	Affected			0.1477	0.2735		3	2	0.0	-14.03
c.3531G>T	E1177D 2D AIThe SynGAP1 missense variant E1177D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact. This conclusion is consistent with the lack of ClinVar evidence, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.566503	Binding	0.542	0.705	0.250											-4.195	Likely Benign	0.162	Likely Benign	Likely Benign										0.210	Likely Benign	-0.74	Neutral	0.029	Benign	0.026	Benign	5.42	Benign	0.05	Affected			0.1477	0.2735		3	2	0.0	-14.03
c.3733G>C	E1245Q 2D AIThe SynGAP1 missense change E1245Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely pathogenic verdict (3 pathogenic vs. 1 benign). High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is not available. Consequently, the majority of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.712013	Disordered	0.387847	Uncertain	0.869	0.554	0.625											-11.323	Likely Pathogenic	0.804	Likely Pathogenic	Ambiguous										0.210	Likely Benign	-2.29	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.0819	0.5952		2	2	0.0	-0.98
c.3765G>C	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.3765G>T	K1255N 2D AIThe SynGAP1 missense variant K1255N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the absence of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-3.99	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.00	Affected			0.2993	0.1302		1	0	0.4	-14.07
c.49T>C	S17P 2D AIThe SynGAP1 missense variant S17P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a benign effect. AlphaMissense‑Optimized independently scores the variant as benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.452228	Uncertain	0.341	0.910	0.375											-3.251	Likely Benign	0.256	Likely Benign	Likely Benign										0.210	Likely Benign	-0.65	Neutral	0.212	Benign	0.010	Benign	4.01	Benign	0.00	Affected			0.2406	0.6473		1	-1	-0.8	10.04
c.550G>C	E184Q 2D AIThe SynGAP1 missense variant E184Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the overall assessment. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.431514	Uncertain	0.348	0.622	0.625											-11.927	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic										0.210	Likely Benign	-2.55	Deleterious	0.990	Probably Damaging	0.815	Possibly Damaging	3.47	Benign	0.00	Affected			0.1688	0.7914		2	2	0.0	-0.98
c.584C>T	A195V 2D AIThe SynGAP1 missense variant A195V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN and AlphaMissense‑Default. High‑accuracy methods give no definitive verdict: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign votes), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.346032	Structured	0.430388	Uncertain	0.363	0.533	0.125											-5.830	Likely Benign	0.924	Likely Pathogenic	Ambiguous										0.210	Likely Benign	-2.63	Deleterious	0.384	Benign	0.070	Benign	4.05	Benign	0.12	Tolerated			0.0782	0.5560		0	0	2.4	28.05
c.1006A>C	K336Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K336Q 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 are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) as benign. Because the predictions are evenly split and the high‑accuracy methods give conflicting results, the variant is best classified as of uncertain significance. This assessment does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.318242	Structured	0.338219	Uncertain	0.396	0.428	0.500											-12.876	Likely Pathogenic	0.829	Likely Pathogenic	Ambiguous	0.02	Likely Benign	0.0	-0.17	Likely Benign	-0.08	Likely Benign	0.18	Likely Benign	0.211	Likely Benign	-3.30	Deleterious	0.801	Possibly Damaging	0.252	Benign	1.58	Pathogenic	0.02	Affected			0.4698	0.1514		1	1	0.4	-0.04
c.131G>T	W44L 2D AIThe SynGAP1 missense variant W44L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Consensus from standard predictors shows a split: benign calls come from REVEL, ESM1b, and FATHMM, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessment is inconclusive: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a 2‑vs‑2 tie, and Foldetta stability analysis is unavailable. Overall, the balance of evidence favors a pathogenic interpretation, with no conflict with ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.301917	Structured	0.431379	Uncertain	0.377	0.748	0.375											-5.743	Likely Benign	0.869	Likely Pathogenic	Ambiguous										0.211	Likely Benign	-4.37	Deleterious	0.659	Possibly Damaging	0.693	Possibly Damaging	3.20	Benign	0.00	Affected			0.2584	0.3413		-2	-2	4.7	-73.05
c.17C>A	A6D 2D AIThe SynGAP1 missense variant A6D is reported in gnomAD (ID 6‑33420281‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.566480	Disordered	0.549054	Binding	0.377	0.920	0.875								6-33420281-C-A			-3.340	Likely Benign	0.210	Likely Benign	Likely Benign										0.211	Likely Benign	0.34	Neutral	0.117	Benign	0.010	Benign	4.07	Benign	0.00	Affected	4.32	1	0.1945	0.2530		-2	0	-5.3	44.01
c.1951G>A	E651K 2D AIThe SynGAP1 E651K missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign calls (REVEL, FoldX, premPS, polyPhen‑2 HumVar, SIFT, FATHMM) and pathogenic calls (PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default). Three tools (Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is uncertain; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.365409	Uncertain	0.955	0.340	0.000											-8.714	Likely Pathogenic	0.818	Likely Pathogenic	Ambiguous	0.11	Likely Benign	0.4	1.15	Ambiguous	0.63	Ambiguous	0.08	Likely Benign	0.211	Likely Benign	-2.92	Deleterious	0.921	Possibly Damaging	0.303	Benign	3.39	Benign	0.17	Tolerated			0.2768	0.5803		0	1	-0.4	-0.94
c.2009T>C	L670P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. Stability‑based methods are inconclusive: FoldX, Rosetta, and the combined Foldetta output are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar assertion; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-4.916	Likely Benign	0.237	Likely Benign	Likely Benign	0.56	Ambiguous	0.3	1.83	Ambiguous	1.20	Ambiguous	-0.25	Likely Benign	0.211	Likely Benign	2.42	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	3.41	Benign	0.26	Tolerated			0.3590	0.1474		-3	-3	-5.4	-16.04
c.2234C>T	P745L 2D AIThe SynGAP1 missense variant P745L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus (majority vote) as Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875											-6.303	Likely Benign	0.121	Likely Benign	Likely Benign										0.211	Likely Benign	-3.79	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.53	Benign	0.01	Affected			0.2205	0.5188		-3	-3	5.4	16.04
c.2317A>C	M773L 2D AIThe SynGAP1 missense variant M773L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-3.458	Likely Benign	0.114	Likely Benign	Likely Benign										0.211	Likely Benign	-0.75	Neutral	0.038	Benign	0.137	Benign	4.29	Benign	0.81	Tolerated			0.1517	0.3529		4	2	1.9	-18.03
c.2317A>T	M773L 2D AIThe SynGAP1 missense variant M773L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess pathogenicity uniformly predict a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the consensus of all available predictions points to a benign impact, and this is consistent with the lack of a ClinVar classification—there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.916222	Binding	0.325	0.893	0.250											-3.458	Likely Benign	0.114	Likely Benign	Likely Benign										0.211	Likely Benign	-0.75	Neutral	0.038	Benign	0.137	Benign	4.29	Benign	0.81	Tolerated			0.1517	0.3529		4	2	1.9	-18.03
c.2799C>A	H933Q 2D AIThe SynGAP1 missense variant H933Q has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to benign (two benign versus one pathogenic vote). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus as benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) is unavailable for this variant. Overall, the preponderance of evidence points to 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.			0.666105	Disordered	0.987531	Binding	0.305	0.862	0.625											-3.042	Likely Benign	0.410	Ambiguous	Likely Benign										0.211	Likely Benign	-2.98	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.54	Benign	0.53	Tolerated			0.1654	0.3938		3	0	-0.3	-9.01
c.2921A>T	D974V 2D AIThe SynGAP1 missense variant D974V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective predictions strongly suggest that D974V is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.964377	Binding	0.389	0.897	0.625											-3.629	Likely Benign	0.351	Ambiguous	Likely Benign										0.211	Likely Benign	-1.49	Neutral	0.001	Benign	0.002	Benign	4.16	Benign	0.01	Affected			0.1449	0.7286		-2	-3	7.7	-15.96
c.2936T>C	F979S 2D AIThe SynGAP1 missense variant F979S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and the AlphaMissense‑Optimized score also indicates a benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for F979S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.977500	Binding	0.274	0.889	0.625											-2.350	Likely Benign	0.718	Likely Pathogenic	Likely Benign										0.211	Likely Benign	-0.05	Neutral	0.451	Benign	0.220	Benign	4.23	Benign	0.01	Affected			0.4397	0.0384		-3	-2	-3.6	-60.10
c.3019A>C	S1007R 2D AIThe SynGAP1 missense variant S1007R is not reported in ClinVar and has no gnomAD entry. 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 methods give opposing results: AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the predictions are split, with an equal number of benign and pathogenic calls, and the high‑accuracy tools disagree. Thus, the variant is most likely pathogenic based on the majority of predictions, and this assessment does not contradict ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-5.441	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.1121	0.3237		0	-1	-3.7	69.11
c.3169A>G	S1057G 2D AIThe SynGAP1 missense variant S1057G is reported in gnomAD (ID 6‑33443721‑A‑G) but has no ClinVar entry. All evaluated in‑silico predictors uniformly classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.869507	Binding	0.413	0.927	0.875								6-33443721-A-G	1	7.20e-7	-1.005	Likely Benign	0.049	Likely Benign	Likely Benign										0.211	Likely Benign	-0.47	Neutral	0.421	Benign	0.111	Benign	5.76	Benign	0.52	Tolerated	3.77	5	0.2654	0.4846		0	1	0.4	-30.03
c.3206A>C	Q1069P 2D AIThe SynGAP1 missense variant Q1069P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.981477	Binding	0.333	0.906	0.875											-3.458	Likely Benign	0.056	Likely Benign	Likely Benign										0.211	Likely Benign	0.75	Neutral	0.977	Probably Damaging	0.722	Possibly Damaging	2.73	Benign	1.00	Tolerated			0.2179	0.5944		0	-1	1.9	-31.01
c.3349G>A	G1117S 2D AIThe SynGAP1 missense variant G1117S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750											-3.890	Likely Benign	0.074	Likely Benign	Likely Benign										0.211	Likely Benign	-0.37	Neutral	0.032	Benign	0.026	Benign	5.08	Benign	0.17	Tolerated			0.2572	0.5111		1	0	-0.4	30.03
c.3701T>G	L1234R 2D AIThe SynGAP1 missense change L1234R occurs in a coiled‑coil domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-15.015	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.211	Likely Benign	-4.52	Deleterious	0.997	Probably Damaging	0.939	Probably Damaging	1.46	Pathogenic	0.00	Affected			0.1061	0.0849		-3	-2	-8.3	43.03
c.3906G>C	L1302F 2D AISynGAP1 missense variant L1302F is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments indicate AlphaMissense‑Optimized predicts benign, whereas the SGM consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta stability analysis is unavailable. Overall, the majority of predictions (five pathogenic versus four benign) lean toward a pathogenic effect. Thus, the variant is most likely pathogenic, a conclusion that contrasts with its current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.889642	Binding	0.429	0.842	0.875					Uncertain		1				-5.674	Likely Benign	0.148	Likely Benign	Likely Benign										0.211	Likely Benign	-2.70	Deleterious	0.960	Probably Damaging	0.657	Possibly Damaging	1.53	Pathogenic	0.00	Affected			0.0721	0.2648		2	0	-1.0	34.02
c.394T>A	F132I 2D AISynGAP1 missense variant F132I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign) and Foldetta results are unavailable. Because the majority of consensus tools predict benign and no ClinVar evidence contradicts this, the variant is most likely benign, although the pathogenic signal from AlphaMissense‑Optimized and the inconclusive SGM Consensus leave some uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.450668	Structured	0.727897	Binding	0.345	0.892	0.250											-6.245	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-3.23	Deleterious	0.084	Benign	0.020	Benign	3.36	Benign	0.00	Affected			0.2306	0.1698		1	0	1.7	-34.02
c.4007A>G	E1336G 2D AIThe SynGAP1 missense variant E1336G is not 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, 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, which would assess protein‑folding stability, has no available result for this variant. Overall, the balance of evidence (five benign vs three pathogenic predictions) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750											-3.574	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.211	Likely Benign	-4.36	Deleterious	0.345	Benign	0.109	Benign	3.20	Benign	0.00	Affected			0.3092	0.6170		0	-2	3.1	-72.06
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.524A>C	Q175P 2D AIThe SynGAP1 missense variant Q175P is reported in gnomAD (ID 6‑33435166‑A‑C) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score the substitution as benign. The consensus from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as likely benign. High‑accuracy predictors corroborate this assessment: AlphaMissense‑Optimized predicts a benign outcome, and the SGM‑Consensus (majority vote) confirms a likely benign status. No high‑accuracy folding‑stability analysis (Foldetta) is available for this residue, so stability effects remain unassessed. Overall, the collective evidence points to a benign impact for Q175P, and this conclusion is consistent with the absence of a pathogenic ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375								6-33435166-A-C	1	6.20e-7	-6.995	Likely Benign	0.432	Ambiguous	Likely Benign										0.211	Likely Benign	1.55	Neutral	0.396	Benign	0.188	Benign	4.20	Benign	1.00	Tolerated	3.61	5	0.2075	0.4584		-1	0	1.9	-31.01
c.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.565C>T	P189S 2D AIThe SynGAP1 missense variant P189S is not 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. Tools that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized; ESM1b remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of computational evidence indicates 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.			0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250											-7.191	In-Between	0.992	Likely Pathogenic	Likely Pathogenic										0.211	Likely Benign	-5.23	Deleterious	0.941	Possibly Damaging	0.531	Possibly Damaging	4.09	Benign	0.15	Tolerated			0.3626	0.6460		1	-1	0.8	-10.04
c.86T>G	M29R 2D AIThe SynGAP1 missense variant M29R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.541878	Disordered	0.438540	Uncertain	0.341	0.883	0.250											-1.708	Likely Benign	0.241	Likely Benign	Likely Benign										0.211	Likely Benign	-0.92	Neutral	0.042	Benign	0.184	Benign	4.23	Benign	0.00	Affected			0.2076	0.1293		0	-1	-6.4	24.99
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.1100T>C	L367P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L367P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict pathogenicity are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, SIFT, and FATHMM; premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Overall, the majority of predictions lean toward a benign effect, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-2.418	Likely Benign	0.160	Likely Benign	Likely Benign	2.13	Destabilizing	0.4	4.05	Destabilizing	3.09	Destabilizing	0.72	Ambiguous	0.212	Likely Benign	-0.50	Neutral	0.627	Possibly Damaging	0.196	Benign	1.72	Pathogenic	0.02	Affected			0.3946	0.1874		-3	-3	-5.4	-16.04
c.1231A>G	I411V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I411V is reported in ClinVar as benign (ClinVar ID 1654508.0) and is not found in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Two tools predict a pathogenic outcome: PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are AlphaMissense‑Default, FoldX, Rosetta, premPS, and Foldetta. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) is uncertain. Overall, the preponderance of evidence points to a benign effect for I411V, which is consistent with its ClinVar classification and does not contradict the reported status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.339366	Uncertain	0.927	0.198	0.000					Likely Benign		1				-6.290	Likely Benign	0.385	Ambiguous	Likely Benign	0.74	Ambiguous	0.0	0.82	Ambiguous	0.78	Ambiguous	0.99	Ambiguous	0.212	Likely Benign	-0.86	Neutral	0.935	Possibly Damaging	0.858	Possibly Damaging	3.90	Benign	0.27	Tolerated	3.38	28	0.1112	0.3526		4	3	-0.3	-14.03	233.3	28.2	-0.2	0.0	-0.2	0.0						X		Potentially Benign	The sec-butyl side chain of Ile411, located in the hydrophobic space between an anti-parallel β sheet strand (res. Pro398-Ile411) and an α helix (res. Asp684-Gln702), packs against multiple residues (e.g., Met409, Arg259). In the variant simulations, the side chain of Val411 is able to favorably fill the same hydrophobic niche despite its slightly smaller size. In short, the residue swap has no apparent negative effect on the structure based on the simulations.
c.2120C>T	A707V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A707V variant is not reported in ClinVar (no ClinVar ID) but is present in gnomAD (variant ID 6‑33441585‑C‑T). Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign classification. Only three tools—Rosetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar—predict pathogenicity, while Foldetta reports an uncertain stability change. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta remains uncertain. Overall, the majority of evidence supports a benign impact for A707V, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000								6-33441585-C-T	1	6.20e-7	-6.479	Likely Benign	0.277	Likely Benign	Likely Benign	0.05	Likely Benign	0.0	2.17	Destabilizing	1.11	Ambiguous	-0.30	Likely Benign	0.212	Likely Benign	-1.62	Neutral	0.991	Probably Damaging	0.912	Probably Damaging	3.45	Benign	1.00	Tolerated	3.50	9	0.0794	0.4048		0	0	2.4	28.05
c.2284G>C	D762H 2D AIThe SynGAP1 D762H missense variant is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-4.643	Likely Benign	0.909	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-2.73	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.08	Pathogenic	0.02	Affected			0.2007	0.9102		1	-1	0.3	22.05
c.2602G>C	D868H 2D AIThe SynGAP1 missense variant D868H is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (variant ID 6‑33443154‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of predictions lean toward a benign impact, and this is not contradicted by 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.			0.525368	Disordered	0.676362	Binding	0.262	0.815	0.250								6-33443154-G-C	1	6.20e-7	-3.358	Likely Benign	0.763	Likely Pathogenic	Likely Benign										0.212	Likely Benign	-2.34	Neutral	1.000	Probably Damaging	0.983	Probably Damaging	2.49	Pathogenic	0.08	Tolerated	3.82	4	0.2258	0.7837		-1	1	0.3	22.05
c.2928T>A	F976L 2D AIThe SynGAP1 missense variant F976L is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443480‑T‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from high‑accuracy predictors and consensus analysis indicates that F976L is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625								6-33443480-T-A	2	1.24e-6	-2.432	Likely Benign	0.825	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-0.87	Neutral	0.264	Benign	0.102	Benign	4.20	Benign	0.53	Tolerated	4.32	2	0.2829	0.3082		2	0	1.0	-34.02
c.2928T>G	F976L 2D AIThe SynGAP1 missense variant F976L is listed in ClinVar (ID 624245.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Only AlphaMissense‑Default predicts a pathogenic outcome. The high‑accuracy consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. AlphaMissense‑Optimized is inconclusive, and no Foldetta (FoldX‑MD/Rosetta stability) result is available. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar designation of uncertainty rather than a definitive pathogenic claim. Thus, the variant is most likely benign, and its predictions do not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625					Uncertain		1				-2.432	Likely Benign	0.825	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-0.87	Neutral	0.264	Benign	0.102	Benign	4.20	Benign	0.53	Tolerated	4.32	2	0.2829	0.3082		2	0	1.0	-34.02
c.3256C>T	P1086S 2D AIThe SynGAP1 missense variant P1086S is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 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 predictions (five pathogenic vs. four benign) lean 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.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000								6-33443808-C-T			-3.165	Likely Benign	0.604	Likely Pathogenic	Likely Benign										0.212	Likely Benign	-3.04	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.78	Benign	0.00	Affected	3.77	5	0.3067	0.4894		-1	1	0.8	-10.04
c.3262A>T	S1088C 2D AIThe SynGAP1 missense variant S1088C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and SIFT. Two tools, AlphaMissense‑Default and ESM1b, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000											-7.532	In-Between	0.547	Ambiguous	Likely Benign										0.212	Likely Benign	-2.33	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.59	Benign	0.01	Affected			0.1571	0.6166		0	-1	3.3	16.06
c.3676C>A	Q1226K 2D AIThe SynGAP1 missense variant Q1226K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence therefore points to a likely pathogenic outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta data are missing. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250											-13.233	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous										0.212	Likely Benign	-3.16	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	1.82	Pathogenic	0.00	Affected			0.1334	0.3199		1	1	-0.4	0.04
c.412A>G	K138E 2D AIThe SynGAP1 missense variant K138E is not 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 (2 vs 2). AlphaMissense‑Optimized specifically predicts pathogenicity, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of predictions lean toward a benign outcome (5 benign vs 4 pathogenic), 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.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-11.902	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.212	Likely Benign	-2.13	Neutral	0.247	Benign	0.125	Benign	3.60	Benign	0.01	Affected			0.3611	0.0974		0	1	0.4	0.94
c.542A>T	H181L 2D AIThe SynGAP1 H181L 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 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and ESM1b; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans pathogenic (2 pathogenic vs 1 benign). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the majority of standard predictors classify the variant as benign, and there is no ClinVar entry to contradict 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.			0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500											-11.014	Likely Pathogenic	0.561	Ambiguous	Likely Benign										0.212	Likely Benign	-3.51	Deleterious	0.267	Benign	0.039	Benign	4.17	Benign	0.04	Affected			0.0734	0.4395		-2	-3	7.0	-23.98
c.1331A>G	K444R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K444R is not reported in ClinVar and has no gnomAD allele. Prediction tools cluster into benign (REVEL, FoldX, SIFT, FATHMM, AlphaMissense‑Optimized) and pathogenic (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). Two tools (Rosetta, premPS) give uncertain results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta predicts benign. No prediction or folding stability result is missing. Overall, six tools favor pathogenicity while five favor benignity, and the high‑accuracy consensus leans toward benign. Thus the variant is most likely pathogenic based on the broader set of predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-10.753	Likely Pathogenic	0.693	Likely Pathogenic	Likely Benign	-0.12	Likely Benign	0.1	-0.61	Ambiguous	-0.37	Likely Benign	0.77	Ambiguous	0.213	Likely Benign	-2.86	Deleterious	0.972	Probably Damaging	0.926	Probably Damaging	3.45	Benign	0.12	Tolerated			0.4597	0.0972		3	2	-0.6	28.01
c.170T>G	L57R 2D AIThe SynGAP1 missense variant L57R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-6.034	Likely Benign	0.810	Likely Pathogenic	Ambiguous										0.213	Likely Benign	-1.55	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.91	Benign	0.00	Affected			0.1245	0.0685		-3	-2	-8.3	43.03
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.2299A>T	I767F 2D AIThe SynGAP1 missense variant I767F is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125											-3.618	Likely Benign	0.162	Likely Benign	Likely Benign										0.213	Likely Benign	-1.37	Neutral	0.003	Benign	0.002	Benign	4.04	Benign	0.06	Tolerated			0.0643	0.3567		1	0	-1.7	34.02
c.2549G>T	G850V 2D AIThe SynGAP1 missense variant G850V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools converge on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G850V, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.540897	Binding	0.312	0.820	0.500											-5.379	Likely Benign	0.081	Likely Benign	Likely Benign										0.213	Likely Benign	-1.74	Neutral	0.960	Probably Damaging	0.679	Possibly Damaging	4.21	Benign	0.02	Affected			0.1255	0.4077		-1	-3	4.6	42.08
c.2669G>T	R890L 2D AIThe SynGAP1 missense variant R890L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign prediction (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑accuracy and consensus predictions indicate a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.531156	Binding	0.284	0.928	0.625											-2.387	Likely Benign	0.389	Ambiguous	Likely Benign										0.213	Likely Benign	-2.74	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	3.98	Benign	0.20	Tolerated			0.1876	0.3406		-3	-2	8.3	-43.03
c.3005A>C	H1002P 2D AIThe SynGAP1 missense variant H1002P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the majority of predictions and the high‑accuracy consensus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500											-4.616	Likely Benign	0.242	Likely Benign	Likely Benign										0.213	Likely Benign	-2.02	Neutral	0.989	Probably Damaging	0.874	Possibly Damaging	2.77	Benign	0.28	Tolerated			0.2015	0.3738		0	-2	1.6	-40.02
c.3022G>C	D1008H 2D AIThe SynGAP1 missense variant D1008H is catalogued in gnomAD (6‑33443574‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, PROVEAN, ESM1b, and FATHMM; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, while Foldetta data are not available. Overall, the majority of evidence points toward a benign effect, and this conclusion aligns with the SGM‑Consensus and the benign consensus of most tools. There is no ClinVar status to contradict this assessment. Thus, the variant is most likely benign, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.919416	Binding	0.280	0.899	0.625								6-33443574-G-C	1	6.20e-7	-3.612	Likely Benign	0.915	Likely Pathogenic	Ambiguous										0.213	Likely Benign	-2.46	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.64	Benign	0.01	Affected	3.77	5	0.2488	0.7228		-1	1	0.3	22.05
c.3394T>G	S1132A 2D AIThe SynGAP1 missense variant S1132A is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.845506	Binding	0.289	0.894	0.750											-3.401	Likely Benign	0.078	Likely Benign	Likely Benign										0.213	Likely Benign	-0.60	Neutral	0.061	Benign	0.013	Benign	5.47	Benign	0.55	Tolerated			0.4416	0.5683		1	1	2.6	-16.00
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.3539T>C	L1180P 2D AISynGAP1 missense variant L1180P is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus prediction and the higher number of benign calls, suggests the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-4.564	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic										0.213	Likely Benign	-1.37	Neutral	0.992	Probably Damaging	0.930	Probably Damaging	2.65	Benign	0.00	Affected			0.3556	0.1155		-3	-3	-5.4	-16.04
c.3610T>G	S1204A 2D AIThe SynGAP1 missense variant S1204A is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.595080	Disordered	0.541098	Binding	0.887	0.587	0.375											-5.134	Likely Benign	0.144	Likely Benign	Likely Benign										0.213	Likely Benign	-0.53	Neutral	0.061	Benign	0.047	Benign	5.45	Benign	1.00	Tolerated			0.4943	0.3167		1	1	2.6	-16.00
c.3839T>A	M1280K 2D AIThe SynGAP1 missense variant M1280K is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods points to a benign impact for M1280K, 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		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875											-2.963	Likely Benign	0.223	Likely Benign	Likely Benign										0.213	Likely Benign	-1.42	Neutral	0.126	Benign	0.041	Benign	2.37	Pathogenic	0.00	Affected			0.1096	0.0488		0	-1	-5.8	-3.02
c.389A>C	Q130P 2D AIThe SynGAP1 missense variant Q130P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.718853	Binding	0.306	0.885	0.375											-0.659	Likely Benign	0.068	Likely Benign	Likely Benign										0.213	Likely Benign	-0.10	Neutral	0.990	Probably Damaging	0.954	Probably Damaging	4.15	Benign	0.03	Affected			0.2414	0.4466		0	-1	1.9	-31.01
c.1153T>A	S385T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S385T is not 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, PROVEAN, polyPhen‑2 HumDiv, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumVar and SIFT 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—AlphaMissense‑Optimized, the SGM‑Consensus, and Foldetta (combining FoldX‑MD and Rosetta outputs)—all indicate a benign effect. Consequently, the variant is most likely benign based on the available 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	C2	0.733139	Disordered	0.425480	Uncertain	0.341	0.925	0.750											-5.904	Likely Benign	0.095	Likely Benign	Likely Benign	0.65	Ambiguous	0.2	0.05	Likely Benign	0.35	Likely Benign	-0.12	Likely Benign	0.214	Likely Benign	-0.31	Neutral	0.140	Benign	0.481	Possibly Damaging	4.64	Benign	0.03	Affected			0.2266	0.6259		1	1	0.1	14.03
c.1368G>C	Q456H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions lean toward a benign impact, and this does not contradict the lack of ClinVar annotation. Thus, based on the available computational evidence, the variant is most likely benign, though a high‑accuracy consensus suggests a possible pathogenic effect that warrants further investigation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-7.993	In-Between	0.598	Likely Pathogenic	Likely Benign	0.74	Ambiguous	0.1	0.39	Likely Benign	0.57	Ambiguous	0.32	Likely Benign	0.214	Likely Benign	-4.07	Deleterious	0.996	Probably Damaging	0.974	Probably Damaging	3.37	Benign	0.19	Tolerated			0.0987	0.2358		3	0	0.3	9.01
c.1368G>T	Q456H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions lean toward a benign impact, and this does not contradict the lack of ClinVar annotation. Thus, based on the available computational evidence, the variant is most likely benign, though a high‑accuracy consensus suggests a possible pathogenic effect that warrants further investigation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000											-7.993	In-Between	0.598	Likely Pathogenic	Likely Benign	0.74	Ambiguous	0.1	0.39	Likely Benign	0.57	Ambiguous	0.32	Likely Benign	0.214	Likely Benign	-4.07	Deleterious	0.996	Probably Damaging	0.974	Probably Damaging	3.37	Benign	0.19	Tolerated			0.0987	0.2358		3	0	0.3	9.01
c.1381G>A	A461T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A461T missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, premPS) returned uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta is also inconclusive. Overall, the balance of evidence favors a benign 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.		GAP	0.179055	Structured	0.292531	Uncertain	0.936	0.151	0.125											-10.885	Likely Pathogenic	0.323	Likely Benign	Likely Benign	1.21	Ambiguous	0.2	0.51	Ambiguous	0.86	Ambiguous	0.65	Ambiguous	0.214	Likely Benign	-3.27	Deleterious	0.508	Possibly Damaging	0.042	Benign	3.40	Benign	0.13	Tolerated			0.1083	0.5930		1	0	-2.5	30.03
c.143T>C	F48S 2D AIThe SynGAP1 missense variant F48S has no ClinVar assertion and is not reported in gnomAD. High‑accuracy predictors: AlphaMissense‑Optimized returned an uncertain classification; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect; Foldetta predictions are unavailable. Among the remaining tools, six predict benign (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM) while two predict pathogenic (SIFT, AlphaMissense‑Default). Based on the aggregate predictions, the variant is most likely benign; this is consistent with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.298791	Structured	0.440452	Uncertain	0.558	0.707	0.125											-6.382	Likely Benign	0.916	Likely Pathogenic	Ambiguous										0.214	Likely Benign	-2.25	Neutral	0.334	Benign	0.099	Benign	3.95	Benign	0.00	Affected			0.4577	0.0901		-3	-2	-3.6	-60.10
c.1452C>A	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN (3 pathogenic vs. 1 benign) and therefore also indicates pathogenicity. AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy consensus supports a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.214	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.1452C>G	F484L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F484L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM, while pathogenic predictions arise from SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, yields an uncertain result. Overall, seven tools predict pathogenicity versus four predicting benign, and the high‑accuracy methods reinforce the pathogenic signal. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.182256	Structured	0.403079	Uncertain	0.798	0.245	0.125											-11.052	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.52	Ambiguous	0.0	1.32	Ambiguous	1.42	Ambiguous	1.20	Destabilizing	0.214	Likely Benign	-5.64	Deleterious	0.054	Benign	0.022	Benign	3.20	Benign	0.04	Affected			0.1737	0.2956		2	0	1.0	-34.02
c.2053T>G	L685V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L685V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability methods provide definitive evidence. Overall, the preponderance of pathogenic predictions, including the SGM Consensus, suggests that the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.162061	Uncertain	0.913	0.280	0.000											-11.418	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	1.87	Ambiguous	0.0	1.15	Ambiguous	1.51	Ambiguous	0.97	Ambiguous	0.214	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.33	Benign	0.02	Affected			0.1414	0.3010		2	1	0.4	-14.03
c.2071A>C	T691P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T691P is listed in ClinVar (ID 648126.0) as Pathogenic and is not reported in gnomAD. Across the broad panel of in‑silico predictors, three tools (REVEL, SIFT, FATHMM) classify the change as benign, whereas the remaining 11 predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score) report it as pathogenic. High‑accuracy assessments further support a deleterious effect: the AlphaMissense‑Optimized model is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and the Foldetta stability analysis (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence indicates that T691P is most likely pathogenic, which is consistent with its ClinVar classification and does not contradict the database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.271308	Uncertain	0.941	0.232	0.000					Likely Pathogenic		1				-13.801	Likely Pathogenic	0.905	Likely Pathogenic	Ambiguous	5.04	Destabilizing	0.4	6.09	Destabilizing	5.57	Destabilizing	1.27	Destabilizing	0.214	Likely Benign	-3.43	Deleterious	1.000	Probably Damaging	0.952	Probably Damaging	3.43	Benign	0.06	Tolerated	3.43	14	0.1466	0.4236		0	-1	-0.9	-3.99	188.9	33.0	0.1	0.0	-0.6	0.0	X	X						Potentially Pathogenic	The hydroxyl side chain of Thr691, located in an α-helix (res. Leu696-Leu685), can form hydrogen bonds with the backbone carbonyl and the side chain guanidinium group of Arg687. This interaction facilitates the simultaneous formation of salt bridges between Arg687 and Glu688 on the same α-helix. Additionally, Thr691 occasionally interacts with the thioether side chain of Met409 in an anti-parallel β-sheet of the C2 domain (res. Ile411-Ala399), although this interaction is not consistently maintained throughout the WT simulations. In the variant simulations, the pyrrolidine side chain of Pro691 lacks hydrogen bond donors, making a similar setup impossible. Moreover, proline lacks a free amide group necessary for hydrogen bonding with the carbonyl group of Arg687, introducing a slight bend in the α-helix and compromising its integrity.
c.2539C>A	Q847K 2D AIThe SynGAP1 missense variant Q847K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Pathogenic verdict. High‑accuracy assessments further indicate that AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus remains Likely Pathogenic; no Foldetta stability data are available. Overall, the majority of predictions lean toward pathogenicity, and this is consistent with the SGM Consensus result. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar annotation exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500											-5.507	Likely Benign	0.736	Likely Pathogenic	Likely Benign										0.214	Likely Benign	-2.82	Deleterious	0.481	Possibly Damaging	0.373	Benign	2.32	Pathogenic	0.00	Affected			0.1694	0.4129		1	1	-0.4	0.04
c.2729G>A	G910D 2D AIThe SynGAP1 missense variant G910D is not reported 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, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.707319	Binding	0.264	0.917	0.250											-4.190	Likely Benign	0.856	Likely Pathogenic	Ambiguous										0.214	Likely Benign	-1.87	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.84	Benign	0.05	Affected			0.1642	0.1477		1	-1	-3.1	58.04
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.3725A>G	E1242G 2D AIThe SynGAP1 missense variant E1242G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and ESM1b, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Optimized also predicts a benign outcome, whereas AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as 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 high‑accuracy predictors points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.557691	Disordered	0.456349	Uncertain	0.870	0.549	0.500											-6.674	Likely Benign	0.528	Ambiguous	Likely Benign										0.214	Likely Benign	-5.33	Deleterious	0.939	Possibly Damaging	0.670	Possibly Damaging	2.19	Pathogenic	0.00	Affected			0.2431	0.4295		0	-2	3.1	-72.06
c.3904T>G	L1302V 2D AIThe SynGAP1 missense variant L1302V is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.889642	Binding	0.429	0.842	0.875											-4.140	Likely Benign	0.082	Likely Benign	Likely Benign										0.214	Likely Benign	-1.71	Neutral	0.004	Benign	0.022	Benign	1.58	Pathogenic	0.00	Affected			0.1603	0.2686		2	1	0.4	-14.03
c.947A>C	N316T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N316T is not 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 AlphaMissense‑Optimized. Those that agree on a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. The remaining tools (AlphaMissense‑Default, ESM1b, Foldetta, premPS, Rosetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta also yields an uncertain stability change. Overall, the majority of available predictions lean toward pathogenicity, and this assessment does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.118441	Structured	0.385187	Uncertain	0.817	0.246	0.125											-7.538	In-Between	0.550	Ambiguous	Likely Benign	2.71	Destabilizing	0.2	1.27	Ambiguous	1.99	Ambiguous	0.57	Ambiguous	0.214	Likely Benign	-3.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.79	Pathogenic	0.08	Tolerated			0.1482	0.8474		0	0	2.8	-13.00
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.1587C>G	I529M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I529M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome; Rosetta is uncertain and therefore treated as unavailable. High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs)—all uniformly indicate a benign effect. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.318242	Structured	0.019545	Uncertain	0.901	0.403	0.000											1.489	Likely Benign	0.063	Likely Benign	Likely Benign	0.10	Likely Benign	0.1	0.68	Ambiguous	0.39	Likely Benign	-0.17	Likely Benign	0.215	Likely Benign	0.71	Neutral	0.035	Benign	0.063	Benign	-1.27	Pathogenic	0.15	Tolerated			0.0673	0.2876		2	1	-2.6	18.03
c.1612G>A	E538K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant E538K has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment indicates that AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) supports a pathogenic outcome, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign stability. Overall, the majority of tools lean toward a benign effect, but the consensus of high‑accuracy predictors and several individual pathogenic scores suggest uncertainty. The variant is most likely benign based on the bulk of 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 Pathogenic	GAP	0.122885	Structured	0.033501	Uncertain	0.938	0.359	0.000											-11.345	Likely Pathogenic	0.922	Likely Pathogenic	Ambiguous	-0.03	Likely Benign	0.0	-0.16	Likely Benign	-0.10	Likely Benign	-0.22	Likely Benign	0.215	Likely Benign	-2.97	Deleterious	0.848	Possibly Damaging	0.294	Benign	3.46	Benign	0.16	Tolerated			0.2257	0.3818		0	1	-0.4	-0.94
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.2762T>C	L921P 2D AIThe SynGAP1 missense variant L921P is recorded in gnomAD (ID 6‑33443314‑T‑C) but has no ClinVar submission. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized; pathogenic calls from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because the votes are split (two benign, one pathogenic, one uncertain). Foldetta, a protein‑folding stability predictor that combines FoldX‑MD and Rosetta outputs, has no reported result for this variant. Consequently, the evidence is evenly divided, with high‑accuracy tools not providing a decisive verdict. The variant is therefore inconclusive; it does not contradict ClinVar status, which currently has no entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375								6-33443314-T-C	1	6.20e-7	-2.087	Likely Benign	0.393	Ambiguous	Likely Benign										0.215	Likely Benign	-1.83	Neutral	0.998	Probably Damaging	0.958	Probably Damaging	2.39	Pathogenic	0.00	Affected	3.77	5	0.3581	0.1343		-3	-3	-5.4	-16.04
c.3083T>C	L1028P 2D AIThe SynGAP1 missense variant L1028P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Taken together, the majority of evidence points to a benign impact for this variant, and there is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500											-3.080	Likely Benign	0.594	Likely Pathogenic	Likely Benign										0.215	Likely Benign	-0.42	Neutral	0.004	Benign	0.010	Benign	2.70	Benign	0.25	Tolerated			0.2846	0.1763		-3	-3	-5.4	-16.04
c.3484C>T	P1162S 2D AIThe SynGAP1 missense variant P1162S is listed in ClinVar (ID 2287942.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic effect are PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑accuracy and consensus predictions lean toward a benign impact. Thus, the variant is most likely benign, which is consistent with its ClinVar “Uncertain” designation rather than contradicting it. 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					Uncertain		1				-2.118	Likely Benign	0.913	Likely Pathogenic	Ambiguous										0.215	Likely Benign	-1.93	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.73	Benign	0.55	Tolerated	3.88	3	0.3386	0.6055		1	-1	0.8	-10.04
c.3554A>T	K1185I 2D AIThe SynGAP1 missense variant K1185I is listed in ClinVar with no pathogenicity classification (ClinVar status: None) and is present in the gnomAD database (gnomAD ID: 6‑33444589‑A‑T). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM, while 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, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which remains unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625								6-33444589-A-T	1	6.20e-7	-5.101	Likely Benign	0.990	Likely Pathogenic	Likely Pathogenic										0.215	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.09	Tolerated	3.82	4	0.1154	0.3108		-3	-2	8.4	-15.01
c.373C>A	P125T 2D AIThe SynGAP1 missense variant P125T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.704227	Binding	0.373	0.878	0.625											-4.780	Likely Benign	0.273	Likely Benign	Likely Benign										0.215	Likely Benign	-3.78	Deleterious	0.036	Benign	0.014	Benign	2.85	Benign	0.01	Affected			0.1502	0.4995		0	-1	0.9	3.99
c.3830A>T	H1277L 2D AIThe SynGAP1 missense variant H1277L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign vs. two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.805725	Binding	0.562	0.718	0.750											-2.949	Likely Benign	0.237	Likely Benign	Likely Benign										0.215	Likely Benign	-7.93	Deleterious	0.224	Benign	0.091	Benign	2.17	Pathogenic	0.00	Affected			0.0822	0.4158		-2	-3	7.0	-23.98
c.3889A>G	R1297G 2D AIThe SynGAP1 missense variant R1297G is reported in gnomAD (ID 6‑33451763‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus itself is Benign; Foldetta results are unavailable. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R1297G is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.895222	Binding	0.511	0.817	0.625								6-33451763-A-G	3	1.86e-6	-2.833	Likely Benign	0.168	Likely Benign	Likely Benign										0.215	Likely Benign	-3.65	Deleterious	0.224	Benign	0.171	Benign	2.56	Benign	0.01	Affected	3.77	5	0.3089	0.2400		-2	-3	4.1	-99.14
c.3906G>T	L1302F 2D AIThe SynGAP1 missense variant L1302F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools that are available indicate a benign outcome (AlphaMissense‑Optimized) while the consensus and stability analyses are missing. Consequently, the overall prediction is ambiguous, but the most reliable evidence points toward a benign effect, and this does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.889642	Binding	0.429	0.842	0.875											-5.674	Likely Benign	0.148	Likely Benign	Likely Benign										0.215	Likely Benign	-2.70	Deleterious	0.960	Probably Damaging	0.657	Possibly Damaging	1.53	Pathogenic	0.00	Affected			0.0721	0.2648		2	0	-1.0	34.02
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.1277A>T	N426I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N426I has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Optimized, and the protein‑folding stability method Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicting pathogenicity, and Foldetta indicating a benign folding stability outcome. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000											-10.158	Likely Pathogenic	0.570	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.0	0.14	Likely Benign	0.41	Likely Benign	0.23	Likely Benign	0.216	Likely Benign	-5.71	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.31	Benign	0.09	Tolerated			0.0656	0.3244		-2	-3	8.0	-0.94
c.1913A>G	K638R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638R is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). In contrast, PROVEAN and polyPhen‑2 HumDiv predict a pathogenic impact, while premPS remains inconclusive. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is benign. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000					Uncertain		1				-2.700	Likely Benign	0.110	Likely Benign	Likely Benign	0.09	Likely Benign	0.1	-0.04	Likely Benign	0.03	Likely Benign	0.53	Ambiguous	0.216	Likely Benign	-2.55	Deleterious	0.649	Possibly Damaging	0.240	Benign	3.41	Benign	0.13	Tolerated	3.37	31	0.4026	0.0975		2	3	-0.6	28.01
c.2131C>A	L711M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L711M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta reports an uncertain stability change, which is treated as unavailable evidence. Overall, the majority of individual predictors (six pathogenic vs. five benign) and the available high‑accuracy results lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000											-9.368	Likely Pathogenic	0.679	Likely Pathogenic	Likely Benign	0.39	Likely Benign	0.0	1.11	Ambiguous	0.75	Ambiguous	1.40	Destabilizing	0.216	Likely Benign	-1.86	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.34	Benign	0.00	Affected			0.0755	0.2758		4	2	-1.9	18.03
c.2584A>T	N862Y 2D AIThe SynGAP1 missense variant N862Y is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors 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—especially the high‑accuracy consensus—suggests the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.525368	Disordered	0.564559	Binding	0.257	0.791	0.250											-8.200	Likely Pathogenic	0.485	Ambiguous	Likely Benign										0.216	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	4.01	Benign	0.06	Tolerated			0.0871	0.6246		-2	-2	2.2	49.07
c.2680G>A	G894R 2D AISynGAP1 missense variant G894R has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Considering the consensus from high‑accuracy tools and the balance of individual predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for G894R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.425700	Uncertain	0.310	0.925	0.750											-5.222	Likely Benign	0.922	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-1.68	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.86	Benign	0.01	Affected			0.0982	0.4332		-3	-2	-4.1	99.14
c.2680G>C	G894R 2D AISynGAP1 missense variant G894R has no ClinVar record and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Considering the consensus from high‑accuracy tools and the balance of individual predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for G894R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.425700	Uncertain	0.310	0.925	0.750											-5.222	Likely Benign	0.922	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-1.68	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.86	Benign	0.01	Affected			0.0982	0.4332		-3	-2	-4.1	99.14
c.2963T>C	L988P 2D AIThe SynGAP1 missense variant L988P is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward pathogenicity. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750											-3.848	Likely Benign	0.703	Likely Pathogenic	Likely Benign										0.216	Likely Benign	-2.96	Deleterious	0.977	Probably Damaging	0.900	Possibly Damaging	2.62	Benign	0.00	Affected			0.3282	0.1698		-3	-3	-5.4	-16.04
c.3059G>T	R1020L 2D AISynGAP1 missense variant R1020L is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive; Foldetta stability analysis is unavailable. Overall, the majority of evidence points toward a pathogenic effect, which contrasts with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.972945	Binding	0.340	0.777	0.500					Uncertain		1				-6.031	Likely Benign	0.907	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-4.03	Deleterious	0.990	Probably Damaging	0.921	Probably Damaging	2.50	Benign	0.00	Affected	3.77	5	0.1898	0.5214		-3	-2	8.3	-43.03
c.323A>T	K108M 2D AIThe SynGAP1 K108M missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which 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 stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.863	Likely Benign	0.909	Likely Pathogenic	Ambiguous										0.216	Likely Benign	-1.64	Neutral	0.999	Probably Damaging	0.990	Probably Damaging	4.03	Benign	0.01	Affected			0.1271	0.4144		0	-1	5.8	3.02
c.3673T>A	S1225T 2D AIThe SynGAP1 missense variant S1225T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) reports likely benign; Foldetta results are not available. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.513880	Disordered	0.441915	Uncertain	0.891	0.544	0.500											-4.409	Likely Benign	0.057	Likely Benign	Likely Benign										0.216	Likely Benign	-0.49	Neutral	0.003	Benign	0.008	Benign	5.50	Benign	0.60	Tolerated			0.0972	0.4618		1	1	0.1	14.03
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.1081C>A	Q361K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361K is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic outcome. High‑accuracy tools that integrate structural and evolutionary information—AlphaMissense‑Optimized, the SGM‑Consensus, and Foldetta (combining FoldX‑MD and Rosetta outputs)—all return benign predictions. No prediction or folding‑stability result is missing or inconclusive. Based on the aggregate evidence, the variant is most likely benign, 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 Benign	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250											-5.147	Likely Benign	0.286	Likely Benign	Likely Benign	0.17	Likely Benign	0.0	0.36	Likely Benign	0.27	Likely Benign	-0.44	Likely Benign	0.217	Likely Benign	1.29	Neutral	0.969	Probably Damaging	0.930	Probably Damaging	1.73	Pathogenic	1.00	Tolerated			0.1739	0.4701		1	1	-0.4	0.04
c.1135T>G	S379A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S379A is reported in gnomAD (variant ID 6‑33438040‑T‑G) but has no entry in ClinVar. All available in‑silico predictors classify the change as benign: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the consensus SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. Consequently, 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	C2	0.728858	Disordered	0.433206	Uncertain	0.327	0.931	0.625								6-33438040-T-G			-4.300	Likely Benign	0.077	Likely Benign	Likely Benign	-0.22	Likely Benign	0.3	1.03	Ambiguous	0.41	Likely Benign	0.10	Likely Benign	0.217	Likely Benign	-0.50	Neutral	0.012	Benign	0.002	Benign	3.91	Benign	0.21	Tolerated	4.32	11	0.5032	0.5555	Strenghten	1	1	2.6	-16.00
c.1297G>C	A433P 2D 3DClick to see structure in 3D Viewer AISynGAP1 A433P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, SIFT, and FATHMM. Those that predict pathogenicity comprise FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. The remaining tools, premPS and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (integrating FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the lack of ClinVar annotation and gnomAD absence. Therefore, the variant is most likely pathogenic, and this prediction 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	0.098513	Structured	0.352258	Uncertain	0.938	0.302	0.000											-9.887	Likely Pathogenic	0.883	Likely Pathogenic	Ambiguous	2.48	Destabilizing	0.0	7.09	Destabilizing	4.79	Destabilizing	0.55	Ambiguous	0.217	Likely Benign	-2.64	Deleterious	0.998	Probably Damaging	0.820	Possibly Damaging	3.37	Benign	0.07	Tolerated			0.1471	0.4150		1	-1	-3.4	26.04
c.1303T>G	L435V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435V has no ClinVar assertion and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—favors pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. With the preponderance of pathogenic calls from both general and high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-7.134	In-Between	0.571	Likely Pathogenic	Likely Benign	2.97	Destabilizing	0.1	2.33	Destabilizing	2.65	Destabilizing	1.36	Destabilizing	0.217	Likely Benign	-2.80	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.23	Benign	0.06	Tolerated			0.1216	0.2628		2	1	0.4	-14.03
c.1387G>A	D463N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Predictions that are uncertain (Foldetta, AlphaMissense‑Optimized, Rosetta) are treated as unavailable and do not influence the overall assessment. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta is uncertain. Overall, the majority of available predictions lean toward a benign effect, and this conclusion does not contradict any ClinVar status (none reported). 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 Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000											-11.428	Likely Pathogenic	0.812	Likely Pathogenic	Ambiguous	0.10	Likely Benign	0.1	1.19	Ambiguous	0.65	Ambiguous	0.40	Likely Benign	0.217	Likely Benign	-4.37	Deleterious	0.880	Possibly Damaging	0.430	Benign	3.33	Benign	0.10	Tolerated			0.1152	0.5531		2	1	0.0	-0.98
c.1660G>A	V554M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V554M is not reported in ClinVar but is present in gnomAD (ID 6‑33438903‑G‑A). Functional prediction tools show a split opinion: benign calls come from REVEL, Rosetta, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default; FoldX, Foldetta, and premPS are inconclusive. High‑accuracy assessment focuses on AlphaMissense‑Optimized, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta. AlphaMissense‑Optimized predicts benign, the SGM Consensus is a tie and thus unavailable, and Foldetta is uncertain, so it is treated as unavailable. Overall, the available evidence leans toward a benign effect, and this does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.020522	Structured	0.007349	Uncertain	0.955	0.226	0.000								6-33438903-G-A	1	6.20e-7	-8.118	Likely Pathogenic	0.671	Likely Pathogenic	Likely Benign	-1.11	Ambiguous	0.0	-0.20	Likely Benign	-0.66	Ambiguous	0.73	Ambiguous	0.217	Likely Benign	-2.26	Neutral	0.994	Probably Damaging	0.867	Possibly Damaging	3.22	Benign	0.00	Affected	3.37	35	0.0743	0.2810		1	2	-2.3	32.06
c.2068T>G	S690A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S690A is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta reports an uncertain stability change, so these results are treated as unavailable. Overall, the balance of evidence favors a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.055536	Structured	0.247926	Uncertain	0.944	0.253	0.000											-8.763	Likely Pathogenic	0.318	Likely Benign	Likely Benign	-0.82	Ambiguous	0.0	-2.17	Stabilizing	-1.50	Ambiguous	0.45	Likely Benign	0.217	Likely Benign	-2.55	Deleterious	0.887	Possibly Damaging	0.738	Possibly Damaging	3.45	Benign	0.21	Tolerated			0.4619	0.3131		1	1	2.6	-16.00
c.2176A>T	R726W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726W has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized, while pathogenic calls come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or stability result is missing or inconclusive. Overall, the majority of tools (seven) predict a benign effect, but the SGM‑Consensus and several high‑accuracy methods indicate pathogenicity, leaving the variant’s clinical significance uncertain. The predictions do not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-10.091	Likely Pathogenic	0.580	Likely Pathogenic	Likely Benign	0.46	Likely Benign	0.1	0.46	Likely Benign	0.46	Likely Benign	0.15	Likely Benign	0.217	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	2.57	Benign	0.01	Affected			0.1161	0.4252		2	-3	3.6	30.03
c.2549G>A	G850E 2D AIThe SynGAP1 missense variant G850E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. When predictions are grouped by consensus, the benign group contains seven tools, whereas the pathogenic group contains two. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation. The variant is most likely benign based on predictions, and there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.540897	Binding	0.312	0.820	0.500											-4.052	Likely Benign	0.247	Likely Benign	Likely Benign										0.217	Likely Benign	-0.60	Neutral	0.770	Possibly Damaging	0.327	Benign	4.28	Benign	0.02	Affected			0.1612	0.4232		0	-2	-3.1	72.06
c.25C>G	H9D 2D AIThe SynGAP1 missense variant H9D has no ClinVar entry and is not reported in gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority of the high‑accuracy tools) is benign, and the Foldetta stability analysis is unavailable. Overall, the consensus of available predictions indicates that the variant is most likely benign, with no conflict with ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750											-2.912	Likely Benign	0.168	Likely Benign	Likely Benign										0.217	Likely Benign	-0.11	Neutral	0.024	Benign	0.002	Benign	4.24	Benign	0.00	Affected			0.2823	0.2893		1	-1	-0.3	-22.05
c.2762T>G	L921R 2D AIThe SynGAP1 missense variant L921R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375											-2.205	Likely Benign	0.563	Ambiguous	Likely Benign										0.217	Likely Benign	-1.19	Neutral	0.994	Probably Damaging	0.912	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1306	0.0761		-3	-2	-8.3	43.03
c.2927T>C	F976S 2D AIThe SynGAP1 missense variant F976S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.975061	Binding	0.311	0.894	0.625											-2.393	Likely Benign	0.432	Ambiguous	Likely Benign										0.217	Likely Benign	-0.73	Neutral	0.292	Benign	0.102	Benign	4.16	Benign	0.49	Tolerated			0.4432	0.1134		-3	-2	-3.6	-60.10
c.325A>T	S109C 2D AIThe SynGAP1 missense variant S109C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus (majority vote) also as Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-6.268	Likely Benign	0.761	Likely Pathogenic	Likely Benign										0.217	Likely Benign	-2.19	Neutral	0.983	Probably Damaging	0.431	Benign	3.46	Benign	0.00	Affected			0.1084	0.5354		0	-1	3.3	16.06
c.3506A>C	E1169A 2D AIThe SynGAP1 missense variant E1169A is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign impact include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, a majority‑vote method from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Considering the consensus of benign‑predicting tools and the SGM‑Consensus outcome, the variant is most likely benign. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.732455	Binding	0.400	0.781	0.625											-2.132	Likely Benign	0.901	Likely Pathogenic	Ambiguous										0.217	Likely Benign	-2.46	Neutral	0.995	Probably Damaging	0.949	Probably Damaging	2.50	Benign	0.00	Affected			0.3714	0.6293		0	-1	5.3	-58.04
c.353T>C	M118T 2D AIThe SynGAP1 missense variant M118T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM‑Consensus) also indicates a likely benign classification, and AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the evidence from multiple independent predictors and the high‑accuracy consensus strongly supports a benign impact. This conclusion is consistent with the lack of any ClinVar pathogenic annotation, so there is no contradiction with existing clinical database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-2.468	Likely Benign	0.454	Ambiguous	Likely Benign										0.217	Likely Benign	-2.41	Neutral	0.396	Benign	0.067	Benign	3.86	Benign	0.08	Tolerated			0.2207	0.2237		-1	-1	-2.6	-30.09
c.3683A>C	E1228A 2D AIThe SynGAP1 missense variant E1228A is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta are unavailable. Overall, the majority of predictions (5 pathogenic vs 4 benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.517562	Disordered	0.447051	Uncertain	0.892	0.546	0.500											-6.902	Likely Benign	0.222	Likely Benign	Likely Benign										0.217	Likely Benign	-3.59	Deleterious	0.910	Possibly Damaging	0.554	Possibly Damaging	2.47	Pathogenic	0.01	Affected			0.2922	0.4105		0	-1	5.3	-58.04
c.3754C>A	Q1252K 2D AIThe SynGAP1 missense variant Q1252K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the predominance of pathogenic predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875											-13.590	Likely Pathogenic	0.878	Likely Pathogenic	Ambiguous										0.217	Likely Benign	-3.22	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1460	0.2518		1	1	-0.4	0.04
c.3857A>G	E1286G 2D AIThe SynGAP1 missense variant E1286G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the balance of evidence (five benign vs four pathogenic predictions) suggests the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant has not been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.817022	Binding	0.544	0.765	0.750											-3.763	Likely Benign	0.171	Likely Benign	Likely Benign										0.217	Likely Benign	-3.36	Deleterious	0.770	Possibly Damaging	0.327	Benign	2.45	Pathogenic	0.01	Affected			0.2904	0.4942		0	-2	3.1	-72.06
c.3997G>C	E1333Q 2D AIThe SynGAP1 missense variant E1333Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while 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, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (3 benign vs. 1 pathogenic votes) also indicates benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign effect for E1333Q, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.953319	Binding	0.347	0.746	0.750											-4.034	Likely Benign	0.746	Likely Pathogenic	Likely Benign										0.217	Likely Benign	-1.84	Neutral	0.980	Probably Damaging	0.968	Probably Damaging	2.83	Benign	0.00	Affected			0.1548	0.7617		2	2	0.0	-0.98
c.578C>A	A193D 2D AIThe SynGAP1 missense variant A193D is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, while the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic), also yields a pathogenic consensus. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that A193D is most likely pathogenic, 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.			0.429200	Structured	0.428386	Uncertain	0.310	0.577	0.125											-7.488	In-Between	0.998	Likely Pathogenic	Likely Pathogenic										0.217	Likely Benign	-3.46	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	3.99	Benign	0.01	Affected			0.1688	0.1835		0	-2	-5.3	44.01
c.1028T>C	V343A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343A 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 AlphaMissense‑Optimized, whereas the remaining tools—SGM‑Consensus, FoldX (uncertain), 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 this: AlphaMissense‑Optimized classifies the variant as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. Overall, the preponderance of evidence points to a pathogenic effect for V343A, 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	C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250											-8.088	Likely Pathogenic	0.588	Likely Pathogenic	Likely Benign	1.66	Ambiguous	0.1	2.33	Destabilizing	2.00	Destabilizing	1.69	Destabilizing	0.218	Likely Benign	-3.15	Deleterious	0.826	Possibly Damaging	0.551	Possibly Damaging	1.63	Pathogenic	0.01	Affected			0.3137	0.3301		0	0	-2.4	-28.05
c.1034T>A	L345Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L345Q is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into benign (REVEL, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM). FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is unavailable. Overall, the majority of predictions lean toward pathogenicity, while the single high‑accuracy tool that is definitive is benign. Thus, the variant is most likely pathogenic based on the collective evidence, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-6.034	Likely Benign	0.213	Likely Benign	Likely Benign	1.32	Ambiguous	0.1	0.86	Ambiguous	1.09	Ambiguous	1.26	Destabilizing	0.218	Likely Benign	-3.67	Deleterious	0.993	Probably Damaging	0.844	Possibly Damaging	1.82	Pathogenic	0.03	Affected			0.0937	0.0842		-2	-2	-7.3	14.97
c.1354G>A	V452I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V452I is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and SIFT, while ESM1b also predicts pathogenicity. Uncertain predictions come from Rosetta and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Taken together, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar “Uncertain” classification, which remains inconclusive. 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					Uncertain		1				-8.985	Likely Pathogenic	0.361	Ambiguous	Likely Benign	-0.08	Likely Benign	0.1	0.51	Ambiguous	0.22	Likely Benign	0.25	Likely Benign	0.218	Likely Benign	-0.99	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.26	Benign	0.05	Affected			0.0630	0.3476		4	3	0.3	14.03
c.1609G>C	A537P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and Rosetta; FoldX and Foldetta are inconclusive. The high‑accuracy consensus (SGM‑Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN indicates a likely benign outcome, while AlphaMissense‑Optimized also predicts benign. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the majority of evidence points to a benign impact for A537P, 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	GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000											0.404	Likely Benign	0.102	Likely Benign	Likely Benign	-0.61	Ambiguous	0.6	2.43	Destabilizing	0.91	Ambiguous	-0.18	Likely Benign	0.218	Likely Benign	0.67	Neutral	0.020	Benign	0.022	Benign	-1.29	Pathogenic	0.35	Tolerated			0.2152	0.3807		1	-1	-3.4	26.04
c.2543G>T	G848V 2D AIThe SynGAP1 missense variant G848V is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443095‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.563942	Binding	0.287	0.816	0.500								6-33443095-G-T	1	6.20e-7	-4.445	Likely Benign	0.255	Likely Benign	Likely Benign										0.218	Likely Benign	-1.39	Neutral	0.977	Probably Damaging	0.856	Possibly Damaging	2.57	Benign	0.02	Affected	4.32	4	0.1184	0.4336		-3	-1	4.6	42.08
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.2686G>C	G896R 2D AIThe SynGAP1 missense variant G896R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Consequently, the evidence is evenly split between benign and pathogenic predictions, with no decisive support from the high‑accuracy or folding‑stability analyses. The variant is therefore most likely of uncertain significance; it does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625											-4.511	Likely Benign	0.897	Likely Pathogenic	Ambiguous										0.218	Likely Benign	-2.45	Neutral	0.999	Probably Damaging	0.967	Probably Damaging	2.44	Pathogenic	0.14	Tolerated			0.0931	0.4228		-3	-2	-4.1	99.14
c.3004C>G	H1002D 2D AIThe SynGAP1 missense variant H1002D is not reported 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		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500											-6.511	Likely Benign	0.852	Likely Pathogenic	Ambiguous										0.218	Likely Benign	-2.09	Neutral	0.891	Possibly Damaging	0.673	Possibly Damaging	2.75	Benign	0.89	Tolerated			0.2597	0.2335		1	-1	-0.3	-22.05
c.3052A>C	T1018P 2D AIThe SynGAP1 missense variant T1018P is not reported 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.849326	Disordered	0.959985	Binding	0.348	0.801	0.500											-2.046	Likely Benign	0.101	Likely Benign	Likely Benign										0.218	Likely Benign	-1.39	Neutral	0.586	Possibly Damaging	0.302	Benign	2.24	Pathogenic	0.02	Affected			0.2155	0.3960		0	-1	-0.9	-3.99
c.3170G>A	S1057N 2D AIThe SynGAP1 missense variant S1057N is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in‑silico predictors classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No tool predicts pathogenicity. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.869507	Binding	0.413	0.927	0.875					Uncertain		1				-6.386	Likely Benign	0.117	Likely Benign	Likely Benign										0.218	Likely Benign	-0.41	Neutral	0.451	Benign	0.129	Benign	5.25	Benign	0.28	Tolerated			0.2232	0.4605		1	1	-2.7	27.03
c.3517A>C	I1173L 2D AIThe SynGAP1 missense variant I1173L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.501700	Disordered	0.653145	Binding	0.521	0.756	0.375											-1.792	Likely Benign	0.202	Likely Benign	Likely Benign										0.218	Likely Benign	-0.30	Neutral	0.152	Benign	0.102	Benign	5.41	Benign	0.97	Tolerated			0.0745	0.3004		2	2	-0.7	0.00
c.352A>C	M118L 2D AIThe SynGAP1 missense variant M118L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) also benign; Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign effect for M118L, and this conclusion does not contradict any ClinVar status, as no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-1.319	Likely Benign	0.206	Likely Benign	Likely Benign										0.218	Likely Benign	-1.09	Neutral	0.000	Benign	0.001	Benign	4.11	Benign	0.03	Affected			0.1835	0.4511		4	2	1.9	-18.03
c.352A>T	M118L 2D AIThe SynGAP1 missense variant M118L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only SIFT indicates a pathogenic effect, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (derived from the four high‑accuracy tools) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for M118L, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.694846	Disordered	0.676867	Binding	0.330	0.883	0.500											-1.319	Likely Benign	0.206	Likely Benign	Likely Benign										0.218	Likely Benign	-1.09	Neutral	0.000	Benign	0.001	Benign	4.11	Benign	0.03	Affected			0.1835	0.4511		4	2	1.9	-18.03
c.476T>A	I159N 2D AIThe SynGAP1 missense variant I159N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default all predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑vs‑2 split. Foldetta, which would assess protein‑folding stability, has no available output for this variant. Overall, the majority of tools (five out of eight) predict pathogenicity, while three predict benign and one is uncertain. Thus, the variant is most likely pathogenic based on current computational 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.			0.454136	Structured	0.529953	Binding	0.278	0.731	0.125											-14.684	Likely Pathogenic	0.891	Likely Pathogenic	Ambiguous										0.218	Likely Benign	-1.93	Neutral	0.995	Probably Damaging	0.986	Probably Damaging	3.82	Benign	0.00	Affected			0.0919	0.0342		-2	-3	-8.0	0.94
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.607G>C	D203H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D203H missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. No prediction or folding result is missing or inconclusive. Overall, the predictions are mixed, but the two high‑accuracy tools favor a benign outcome, giving a slight bias toward benign. Thus, the variant is most likely benign, 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	PH	0.314870	Structured	0.427620	Uncertain	0.740	0.407	0.125											-9.130	Likely Pathogenic	0.593	Likely Pathogenic	Likely Benign	0.00	Likely Benign	0.1	0.18	Likely Benign	0.09	Likely Benign	-0.04	Likely Benign	0.218	Likely Benign	-3.28	Deleterious	0.999	Probably Damaging	0.936	Probably Damaging	3.98	Benign	0.02	Affected			0.0962	0.4815		1	-1	0.3	22.05
c.883A>T	T295S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T295S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; premPS is inconclusive. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority (3 benign vs. 1 pathogenic); and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.401658	Structured	0.295548	Uncertain	0.881	0.288	0.125											-4.904	Likely Benign	0.335	Likely Benign	Likely Benign	-0.16	Likely Benign	0.2	0.28	Likely Benign	0.06	Likely Benign	0.54	Ambiguous	0.218	Likely Benign	-2.16	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	2.02	Pathogenic	0.14	Tolerated			0.3910	0.4473		1	1	-0.1	-14.03
c.1501A>C	I501L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I501L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, Rosetta, Foldetta, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar) and SIFT. Uncertain or inconclusive results are reported for FoldX, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Benign, all supporting a non‑deleterious effect. Based on the preponderance of benign predictions and the concordant high‑accuracy tools, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.079919	Structured	0.366596	Uncertain	0.886	0.153	0.000											-7.348	In-Between	0.282	Likely Benign	Likely Benign	0.78	Ambiguous	0.2	-0.34	Likely Benign	0.22	Likely Benign	0.86	Ambiguous	0.219	Likely Benign	-1.92	Neutral	0.930	Possibly Damaging	0.985	Probably Damaging	3.51	Benign	0.05	Affected			0.0817	0.2261		2	2	-0.7	0.00
c.1993T>A	Y665N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 Y665N variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Default) give uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of conventional predictors lean toward a benign impact, and this assessment does not contradict ClinVar status (none). Thus, the variant is most likely benign based on the prevailing predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-11.189	Likely Pathogenic	0.470	Ambiguous	Likely Benign	1.11	Ambiguous	0.1	1.43	Ambiguous	1.27	Ambiguous	0.50	Likely Benign	0.219	Likely Benign	-3.03	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.50	Benign	0.88	Tolerated			0.1929	0.0573		-2	-2	-2.2	-49.07
c.2284G>T	D762Y 2D AIThe SynGAP1 D762Y variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas a larger group predicts a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; Foldetta (a protein‑folding stability approach combining FoldX‑MD and Rosetta) has no available output for this variant. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.910475	Binding	0.308	0.859	0.125											-6.959	Likely Benign	0.905	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-3.24	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.07	Pathogenic	0.01	Affected			0.0700	0.7929		-4	-3	2.2	48.09
c.2357T>C	L786P 2D AISynGAP1 missense variant L786P is reported in gnomAD (ID 6‑33442909‑T‑C) but has no ClinVar entry. Functional prediction tools show discordant results: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized reports a benign effect, SGM‑Consensus confirms a likely pathogenic outcome, and Foldetta results are unavailable. Overall, the majority of conventional tools and the SGM‑Consensus support a pathogenic interpretation, while one high‑accuracy tool suggests benign. No ClinVar status is present, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750								6-33442909-T-C			-3.217	Likely Benign	0.656	Likely Pathogenic	Likely Benign										0.219	Likely Benign	-4.06	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.00	Affected	3.77	5	0.3343	0.1814		-3	-3	-5.4	-16.04
c.2488C>T	P830S 2D AIThe SynGAP1 missense variant P830S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and there is no ClinVar classification to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.618152	Binding	0.333	0.874	0.500											-4.629	Likely Benign	0.251	Likely Benign	Likely Benign										0.219	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.28	Tolerated			0.3496	0.5450		1	-1	0.8	-10.04
c.2621A>C	Q874P 2D AIThe SynGAP1 missense variant Q874P is reported in gnomAD (ID 6‑33443173‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar classification (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.635258	Binding	0.289	0.873	0.250								6-33443173-A-C	9	5.58e-6	-4.622	Likely Benign	0.125	Likely Benign	Likely Benign										0.219	Likely Benign	-2.89	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.77	Benign	0.00	Affected	3.77	5	0.2373	0.5911		-1	0	1.9	-31.01
c.2957A>G	E986G 2D AIThe SynGAP1 missense variant E986G is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with the ClinVar status, which currently contains no classification for E986G. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.750527	Disordered	0.929726	Binding	0.349	0.902	0.750											-5.584	Likely Benign	0.834	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-3.14	Deleterious	0.924	Possibly Damaging	0.784	Possibly Damaging	2.13	Pathogenic	0.00	Affected			0.2866	0.6225		0	-2	3.1	-72.06
c.3021T>A	S1007R 2D AIThe SynGAP1 missense variant S1007R 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 include 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 (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the evidence leans toward a pathogenic interpretation, with no ClinVar status to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-5.441	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.1121	0.3237		0	-1	-3.7	69.11
c.3021T>G	S1007R 2D AISynGAP1 missense variant S1007R has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). 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, while the SGM‑Consensus (a majority vote of four high‑accuracy predictors) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the evidence is split, with an equal number of benign and pathogenic predictions. The variant is most likely pathogenic based on the presence of several high‑confidence pathogenic calls, and this assessment does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-5.441	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic										0.219	Likely Benign	-1.93	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.65	Benign	0.01	Affected			0.1121	0.3237		0	-1	-3.7	69.11
c.3593A>T	Y1198F 2D AIThe SynGAP1 missense variant Y1198F is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessments further support a deleterious effect: the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as Likely Pathogenic, and AlphaMissense‑Optimized remains uncertain; Foldetta, a protein‑folding stability method, has no available output for this variant. Overall, the preponderance of evidence (five pathogenic vs. two benign predictions) indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-7.508	In-Between	0.853	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-2.87	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	1.55	Pathogenic	0.13	Tolerated			0.1780	0.2571		7	3	4.1	-16.00
c.3649G>C	E1217Q 2D AIThe SynGAP1 missense variant E1217Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of tools (five pathogenic vs. three benign) and the SGM Consensus support a pathogenic classification, which does not contradict the lack of ClinVar annotation. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.599170	Disordered	0.493043	Uncertain	0.877	0.563	0.250											-8.887	Likely Pathogenic	0.398	Ambiguous	Likely Benign										0.219	Likely Benign	-2.16	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.0949	0.4745		2	2	0.0	-0.98
c.3687A>C	Q1229H 2D AIThe SynGAP1 missense variant Q1229H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evaluated predictors (five out of nine) indicate a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. 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.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-6.215	Likely Benign	0.505	Ambiguous	Likely Benign										0.219	Likely Benign	-3.36	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.05	Affected			0.0948	0.2494		3	0	0.3	9.01
c.3687A>T	Q1229H 2D AIThe SynGAP1 missense variant Q1229H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evaluated predictors (five out of nine) indicate a pathogenic impact, so the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375											-6.215	Likely Benign	0.505	Ambiguous	Likely Benign										0.219	Likely Benign	-3.36	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.05	Affected			0.0948	0.2494		3	0	0.3	9.01
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.3845A>G	E1282G 2D AIThe SynGAP1 missense variant E1282G is reported in gnomAD (ID 6‑33447893‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Taken together, the overwhelming majority of predictions support a benign impact, and there is no ClinVar classification to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.817364	Binding	0.465	0.725	0.875								6-33447893-A-G			-2.649	Likely Benign	0.104	Likely Benign	Likely Benign										0.219	Likely Benign	-1.25	Neutral	0.000	Benign	0.001	Benign	2.68	Benign	0.00	Affected			0.2729	0.5284		0	-2	3.1	-72.06
c.485G>T	R162L 2D AIThe SynGAP1 missense variant R162L is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, giving six concordant benign calls. Two tools predict a pathogenic effect: ESM1b and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.516348	Binding	0.315	0.692	0.250											-9.952	Likely Pathogenic	0.840	Likely Pathogenic	Ambiguous										0.219	Likely Benign	-1.83	Neutral	0.001	Benign	0.003	Benign	4.05	Benign	0.15	Tolerated			0.1888	0.5894		-3	-2	8.3	-43.03
c.956C>G	A319G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A319G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict benign or likely benign. In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM predict pathogenicity, while Rosetta remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.179055	Structured	0.410405	Uncertain	0.879	0.254	0.125											-6.505	Likely Benign	0.148	Likely Benign	Likely Benign	0.11	Likely Benign	0.4	0.56	Ambiguous	0.34	Likely Benign	0.39	Likely Benign	0.219	Likely Benign	-1.83	Neutral	0.994	Probably Damaging	0.900	Possibly Damaging	1.89	Pathogenic	0.09	Tolerated			0.2345	0.4532		1	0	-2.2	-14.03
c.986G>T	R329L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R329L has no ClinVar entry and is not reported in gnomAD. Consensus from standard prediction tools shows a split: benign calls come from REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar, while pathogenic calls arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked uncertain (Rosetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments give a mixed picture: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the majority of tools lean toward pathogenicity, but the folding‑stability evidence suggests a benign effect. Given the lack of ClinVar annotation, there is no contradiction. The variant is most likely pathogenic based on the preponderance of pathogenic predictions, though the benign folding‑stability result introduces uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.376086	Uncertain	0.887	0.479	0.250											-10.186	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	-0.09	Likely Benign	0.4	0.53	Ambiguous	0.22	Likely Benign	0.54	Ambiguous	0.219	Likely Benign	-4.81	Deleterious	0.653	Possibly Damaging	0.361	Benign	4.02	Benign	0.01	Affected			0.1827	0.4121		-3	-2	8.3	-43.03
c.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.152T>G	I51S 2D AIThe SynGAP1 missense variant I51S is not 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 and AlphaMissense‑Default. The remaining tools, ESM1b and AlphaMissense‑Optimized, are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign (2 benign vs. 1 pathogenic vote). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000											-7.603	In-Between	0.879	Likely Pathogenic	Ambiguous										0.220	Likely Benign	-1.39	Neutral	0.182	Benign	0.099	Benign	4.15	Benign	0.00	Affected			0.3142	0.0957		-1	-2	-5.3	-26.08
c.2166C>G	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign stability. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation (none is available). Thus, based on the current computational predictions, the S722R variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.220	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.2281C>G	R761G 2D AIThe SynGAP1 missense variant R761G is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score it as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy methods reinforce the benign prediction: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign, with no contradictory Foldetta data. Overall, the majority of evidence supports a benign classification, and this is consistent with the lack of ClinVar annotation; there is no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.538167	Disordered	0.900613	Binding	0.353	0.865	0.250											-4.453	Likely Benign	0.427	Ambiguous	Likely Benign										0.220	Likely Benign	-2.07	Neutral	0.992	Probably Damaging	0.900	Possibly Damaging	2.70	Benign	0.83	Tolerated			0.3333	0.3217		-3	-2	4.1	-99.14
c.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.29G>C	R10P 2D AIThe SynGAP1 missense variant R10P is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33420293‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) is benign; Foldetta results are unavailable. Overall, the collective evidence points to a benign effect for R10P, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.513657	Binding	0.330	0.915	0.625					Uncertain		2	6-33420293-G-C	2	1.30e-6	-3.772	Likely Benign	0.162	Likely Benign	Likely Benign										0.220	Likely Benign	-0.05	Neutral	0.233	Benign	0.026	Benign	4.13	Benign	0.00	Affected	4.32	1	0.2261	0.5245		0	-2	2.9	-59.07
c.3011A>T	H1004L 2D AIThe SynGAP1 missense variant H1004L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs two benign votes). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750											-5.179	Likely Benign	0.716	Likely Pathogenic	Likely Benign										0.220	Likely Benign	-3.14	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.75	Benign	0.55	Tolerated			0.1223	0.6026		-2	-3	7.0	-23.98
c.3157A>G	S1053G 2D AIThe SynGAP1 missense variant S1053G is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly suggests that S1053G is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875											-1.016	Likely Benign	0.050	Likely Benign	Likely Benign										0.220	Likely Benign	-0.57	Neutral	0.001	Benign	0.002	Benign	5.32	Benign	0.59	Tolerated			0.2724	0.5046		1	0	0.4	-30.03
c.3157A>T	S1053C 2D AIThe SynGAP1 missense variant S1053C is catalogued in gnomAD (ID 6‑33443709‑A‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The ESM1b score is uncertain, providing no clear direction. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the majority of reliable predictors classify S1053C as benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875								6-33443709-A-T			-7.574	In-Between	0.095	Likely Benign	Likely Benign										0.220	Likely Benign	-0.61	Neutral	0.977	Probably Damaging	0.777	Possibly Damaging	5.30	Benign	0.11	Tolerated	3.77	5	0.1675	0.5895		-1	0	3.3	16.06
c.3400A>T	T1134S 2D AIThe SynGAP1 missense variant T1134S is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), also reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this 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		0.885302	Disordered	0.813034	Binding	0.335	0.885	0.875											-3.015	Likely Benign	0.089	Likely Benign	Likely Benign										0.220	Likely Benign	-0.42	Neutral	0.007	Benign	0.009	Benign	5.47	Benign	0.09	Tolerated			0.3189	0.4666		1	1	-0.1	-14.03
c.3482T>G	M1161R 2D AIThe SynGAP1 missense variant M1161R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, SIFT, and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as likely pathogenic; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.580690	Disordered	0.864109	Binding	0.372	0.830	0.375											-2.653	Likely Benign	0.995	Likely Pathogenic	Likely Pathogenic										0.220	Likely Benign	-2.97	Deleterious	0.968	Probably Damaging	0.978	Probably Damaging	2.18	Pathogenic	0.13	Tolerated			0.1689	0.0809		0	-1	-6.4	24.99
c.3599A>C	E1200A 2D AIThe SynGAP1 E1200A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy AlphaMissense‑Optimized score is benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (benign), FATHMM (benign), and PROVEAN (pathogenic), is benign. Foldetta results are unavailable. Overall, the balance of evidence (five benign versus four pathogenic predictions, with a benign SGM Consensus and high‑accuracy benign AlphaMissense‑Optimized) indicates that the variant is most likely benign. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.545602	Disordered	0.458056	Uncertain	0.889	0.596	0.250											-3.115	Likely Benign	0.505	Ambiguous	Likely Benign										0.220	Likely Benign	-2.61	Deleterious	0.994	Probably Damaging	0.926	Probably Damaging	2.72	Benign	0.02	Affected			0.2946	0.4513		0	-1	5.3	-58.04
c.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.385T>C	S129P 2D AIThe SynGAP1 missense variant S129P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools, including the high‑accuracy predictors, indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.713635	Binding	0.311	0.880	0.625											-2.469	Likely Benign	0.237	Likely Benign	Likely Benign										0.220	Likely Benign	-0.09	Neutral	0.454	Possibly Damaging	0.133	Benign	4.11	Benign	0.32	Tolerated			0.1998	0.4989		1	-1	-0.8	10.04
c.3914C>G	T1305R 2D AIThe SynGAP1 missense variant T1305R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.894658	Binding	0.390	0.873	0.875											-2.945	Likely Benign	0.194	Likely Benign	Likely Benign										0.220	Likely Benign	-1.33	Neutral	0.027	Benign	0.114	Benign	2.75	Benign	0.01	Affected			0.1115	0.3214		-1	-1	-3.8	55.08
c.605A>C	E202A 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E202A missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools (AlphaMissense‑Default and ESM1b) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and therefore unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.363090	Structured	0.429450	Uncertain	0.712	0.415	0.125											-7.222	In-Between	0.538	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.14	Likely Benign	0.14	Likely Benign	0.19	Likely Benign	0.220	Likely Benign	-4.05	Deleterious	0.948	Possibly Damaging	0.484	Possibly Damaging	4.02	Benign	0.02	Affected			0.3903	0.6468		0	-1	5.3	-58.04
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.1792C>G	L598V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L598V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as inconclusive. Overall, the majority of evidence points to a pathogenic impact, 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	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000					Uncertain		1				-10.002	Likely Pathogenic	0.578	Likely Pathogenic	Likely Benign	1.89	Ambiguous	0.1	1.58	Ambiguous	1.74	Ambiguous	1.01	Destabilizing	0.221	Likely Benign	-2.92	Deleterious	0.944	Possibly Damaging	0.786	Possibly Damaging	3.21	Benign	0.02	Affected	3.37	35	0.1082	0.1795		2	1	0.4	-14.03	218.4	29.6	0.0	0.0	0.8	0.0						X		Potentially Benign	The iso-butyl side chain of Leu598, located on an α helix (res. Glu582-Met603), packs hydrophobically with other hydrophobic residues in the inter-helix space (e.g., Ile602, Phe594, Ile510).In the variant simulations, Val598, which has similar size and physicochemical properties to leucine, resides in the inter-helix hydrophobic space in a similar manner to Leu598 in the WT. This causes no negative effects on the protein structure.
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.2166C>A	S722R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375											-10.731	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.05	Likely Benign	0.1	-0.03	Likely Benign	0.01	Likely Benign	0.72	Ambiguous	0.221	Likely Benign	-2.66	Deleterious	0.999	Probably Damaging	0.948	Probably Damaging	2.52	Benign	0.09	Tolerated			0.0886	0.2797		0	-1	-3.7	69.11
c.2359C>T	P787S 2D AIThe SynGAP1 P787S variant is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33442911‑C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized, while those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic majority. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750					Uncertain		1	6-33442911-C-T	3	1.86e-6	-4.203	Likely Benign	0.564	Ambiguous	Likely Benign										0.221	Likely Benign	-3.81	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.48	Pathogenic	0.02	Affected	3.64	6	0.3420	0.4675		-1	1	0.8	-10.04
c.2365C>T	P789S 2D AIThe SynGAP1 P789S variant has no ClinVar entry (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify it as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, with five tools supporting a deleterious effect versus three supporting benignity. This prediction does not contradict ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-4.793	Likely Benign	0.409	Ambiguous	Likely Benign										0.221	Likely Benign	-4.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.19	Pathogenic	0.00	Affected			0.3100	0.3436		1	-1	0.8	-10.04
c.3169A>C	S1057R 2D AIThe SynGAP1 missense variant S1057R is catalogued in gnomAD (ID 6‑33443721‑A‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.869507	Binding	0.413	0.927	0.875								6-33443721-A-C			-6.648	Likely Benign	0.379	Ambiguous	Likely Benign										0.221	Likely Benign	-0.24	Neutral	0.677	Possibly Damaging	0.168	Benign	5.30	Benign	0.21	Tolerated	3.77	5	0.1584	0.3620		-1	0	-3.7	69.11
c.3362G>A	S1121N 2D AIThe SynGAP1 missense variant S1121N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the consensus of the majority of predictors and the high‑accuracy tools points to a benign classification, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875											-6.564	Likely Benign	0.105	Likely Benign	Likely Benign										0.221	Likely Benign	-0.12	Neutral	0.802	Possibly Damaging	0.266	Benign	5.50	Benign	0.00	Affected			0.1980	0.4211		1	1	-2.7	27.03
c.3787A>G	I1263V 2D AIThe SynGAP1 missense variant I1263V is not 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), ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two benign vs. two pathogenic votes), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000											-4.230	Likely Benign	0.729	Likely Pathogenic	Likely Benign										0.221	Likely Benign	-0.83	Neutral	0.437	Benign	0.170	Benign	1.99	Pathogenic	0.00	Affected			0.1136	0.3102		4	3	-0.3	-14.03
c.3893A>T	Q1298L 2D AIThe SynGAP1 missense variant Q1298L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, PROVEAN and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.895297	Binding	0.410	0.821	0.750											-2.251	Likely Benign	0.147	Likely Benign	Likely Benign										0.221	Likely Benign	-3.04	Deleterious	0.224	Benign	0.078	Benign	2.79	Benign	0.04	Affected			0.0667	0.4164		-2	-2	7.3	-14.97
c.4007A>T	E1336V 2D AIThe SynGAP1 missense variant E1336V has no ClinVar record (ClinVar status: None) and is not present in gnomAD (gnomAD ID: None). 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. AlphaMissense‑Optimized is reported as uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a tie (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal split between benign and pathogenic calls and no evidence from ClinVar to contradict this uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.865454	Disordered	0.973342	Binding	0.336	0.717	0.750											-3.367	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.221	Likely Benign	-4.46	Deleterious	0.789	Possibly Damaging	0.348	Benign	3.18	Benign	0.00	Affected			0.0991	0.7425		-2	-2	7.7	-29.98
c.421A>T	I141F 2D AIThe SynGAP1 missense variant I141F is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2). Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, with no conflict with 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											-9.621	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.221	Likely Benign	-1.82	Neutral	0.001	Benign	0.002	Benign	3.57	Benign	0.01	Affected			0.0489	0.2775		1	0	-1.7	34.02
c.509G>A	R170Q 2D AISynGAP1 missense variant R170Q is listed in ClinVar as Pathogenic and is not reported in gnomAD. Computational predictors show a 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. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive; Foldetta stability analysis is unavailable. Thus, no single method or high‑accuracy consensus strongly supports pathogenicity. The variant is most likely benign according to the current computational evidence, which contradicts the ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.480142	Structured	0.492928	Uncertain	0.406	0.661	0.250					Pathogenic/Likely path.		6				-9.021	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous										0.221	Likely Benign	-2.31	Neutral	0.947	Possibly Damaging	0.342	Benign	3.91	Benign	0.00	Affected	3.74	4	0.2524	0.2299		1	1	1.0	-28.06																10.1016/j.ajhg.2020.11.011
c.119A>T	D40V 2D AIThe SynGAP1 missense variant D40V 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 SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.384043	Structured	0.432002	Uncertain	0.319	0.769	0.375											-3.350	Likely Benign	0.431	Ambiguous	Likely Benign										0.222	Likely Benign	-1.16	Neutral	0.028	Benign	0.088	Benign	4.00	Benign	0.00	Affected			0.1679	0.8357		-2	-3	7.7	-15.96
c.1305G>C	L435F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, providing no definitive evidence for either outcome. Given the preponderance of pathogenic predictions and the lack of any ClinVar annotation to contradict this assessment, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-11.871	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	0.95	Ambiguous	0.73	Ambiguous	0.69	Ambiguous	0.222	Likely Benign	-3.75	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.26	Benign	0.01	Affected			0.0587	0.2723		2	0	-1.0	34.02
c.1305G>T	L435F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435F is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (Likely Pathogenic). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also uncertain, providing no definitive evidence for either outcome. Given the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000											-11.871	Likely Pathogenic	0.932	Likely Pathogenic	Ambiguous	0.51	Ambiguous	0.1	0.95	Ambiguous	0.73	Ambiguous	0.69	Ambiguous	0.222	Likely Benign	-3.75	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	3.26	Benign	0.01	Affected			0.0587	0.2723		2	0	-1.0	34.02
c.1432G>C	E478Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E478Q is listed in gnomAD (ID 6‑33438464‑G‑C) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑vs‑2 split. Overall, the majority of evidence (nine benign vs three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.264545	Structured	0.414660	Uncertain	0.787	0.249	0.000								6-33438464-G-C	1	6.20e-7	-9.881	Likely Pathogenic	0.603	Likely Pathogenic	Likely Benign	-0.04	Likely Benign	0.0	0.31	Likely Benign	0.14	Likely Benign	0.07	Likely Benign	0.222	Likely Benign	-2.49	Neutral	0.623	Possibly Damaging	0.199	Benign	3.40	Benign	0.14	Tolerated	3.37	34	0.1027	0.5867		2	2	0.0	-0.98
c.1910C>T	S637F 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S637F is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, premPS, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. The high‑accuracy consensus (SGM‑Consensus) aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and yields a pathogenic verdict. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, predicts a benign effect. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points toward a pathogenic impact, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000											-13.266	Likely Pathogenic	0.831	Likely Pathogenic	Ambiguous	0.01	Likely Benign	0.1	0.96	Ambiguous	0.49	Likely Benign	0.49	Likely Benign	0.222	Likely Benign	-3.92	Deleterious	0.985	Probably Damaging	0.681	Possibly Damaging	3.35	Benign	0.01	Affected			0.0780	0.4126		-3	-2	3.6	60.10
c.2297C>A	S766Y 2D AIThe SynGAP1 missense variant S766Y is reported in gnomAD (ID 6‑33442455‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) predicts pathogenic, and no Foldetta stability data are available. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.405110	Structured	0.923125	Binding	0.338	0.874	0.250								6-33442455-C-A			-8.636	Likely Pathogenic	0.641	Likely Pathogenic	Likely Benign										0.222	Likely Benign	-2.67	Deleterious	0.990	Probably Damaging	0.856	Possibly Damaging	4.09	Benign	0.00	Affected	3.64	6	0.0794	0.5609		-2	-3	-0.5	76.10
c.2435C>G	P812R 2D AIThe SynGAP1 P812R missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of standard predictors indicate a pathogenic impact, while the most accurate tools provide no definitive evidence. Thus, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.784	Likely Benign	0.799	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-2.70	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	2.77	Benign	0.01	Affected			0.1285	0.3525		0	-2	-2.9	59.07
c.2447C>A	S816Y 2D AIThe SynGAP1 missense variant S816Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default, all of which classify the substitution as deleterious. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized yields an uncertain result, while Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus, the variant is most likely pathogenic; this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.747189	Binding	0.347	0.898	0.375											-8.369	Likely Pathogenic	0.880	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-2.83	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	2.60	Benign	0.03	Affected			0.0668	0.4741		-3	-2	-0.5	76.10
c.2488C>A	P830T 2D AIThe SynGAP1 missense variant P830T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for P830T, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.618152	Binding	0.333	0.874	0.500											-4.697	Likely Benign	0.192	Likely Benign	Likely Benign										0.222	Likely Benign	-3.56	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.67	Benign	0.02	Affected			0.1519	0.5970		0	-1	0.9	3.99
c.3265G>A	G1089R 2D AIThe SynGAP1 missense variant G1089R is catalogued in gnomAD (ID 6‑33443817‑G‑A) but has no ClinVar entry. Functional prediction tools split in a 6‑to‑3 ratio: benign calls come from REVEL, polyPhen‑2 HumVar, and ESM1b, while pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an Uncertain result, and no Foldetta stability assessment is available. Overall, the majority of high‑confidence predictors lean toward pathogenicity, and this assessment does not conflict with ClinVar status, which is currently unreported. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000								6-33443817-G-A	1	6.35e-7	-4.757	Likely Benign	0.897	Likely Pathogenic	Ambiguous										0.222	Likely Benign	-3.13	Deleterious	0.896	Possibly Damaging	0.325	Benign	2.42	Pathogenic	0.01	Affected	3.77	5	0.0934	0.4415		-2	-3	-4.1	99.14
c.3934G>C	A1312P 2D AIThe SynGAP1 missense variant A1312P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.767246	Disordered	0.971112	Binding	0.392	0.902	0.750											-2.488	Likely Benign	0.076	Likely Benign	Likely Benign										0.222	Likely Benign	-1.64	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	3.12	Benign	0.00	Affected			0.2208	0.5820		1	-1	-3.4	26.04
c.866T>C	M289T 2D AIThe SynGAP1 missense variant M289T is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts a benign effect. Taken together, the majority of evidence indicates that M289T is most likely benign, and this conclusion does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000					Uncertain		1				-4.668	Likely Benign	0.238	Likely Benign	Likely Benign	0.73	Ambiguous	0.1	0.17	Likely Benign	0.45	Likely Benign	-0.01	Likely Benign	0.222	Likely Benign	-0.47	Neutral	0.801	Possibly Damaging	0.315	Benign	1.83	Pathogenic	0.57	Tolerated			0.1657	0.1534		-1	-1	-2.6	-30.09
c.1186G>A	G396S 2D AIThe SynGAP1 missense variant G396S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. No tool predicts pathogenicity. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500											-3.934	Likely Benign	0.088	Likely Benign	Likely Benign	1.76	Ambiguous	1.6	1.12	Ambiguous	1.44	Ambiguous	0.10	Likely Benign	0.223	Likely Benign	-0.99	Neutral	0.004	Benign	0.003	Benign	3.93	Benign	0.56	Tolerated			0.2668	0.4894		1	0	-0.4	30.03
c.2579T>C	V860A 2D AIThe SynGAP1 missense variant V860A is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only SIFT predicts pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for V860A, 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		0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250											-3.379	Likely Benign	0.161	Likely Benign	Likely Benign										0.223	Likely Benign	-0.91	Neutral	0.393	Benign	0.185	Benign	4.20	Benign	0.00	Affected			0.3215	0.2723		0	0	-2.4	-28.05
c.2830G>A	G944S 2D AIThe SynGAP1 missense variant G944S is listed in ClinVar as a benign alteration (ClinVar ID 833552.0) and is present in the gnomAD database (gnomAD ID 6‑33443382‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available for this variant. Overall, the majority of computational evidence supports a benign 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 Benign		0.977651	Disordered	0.852408	Binding	0.360	0.923	0.750					Benign		1	6-33443382-G-A	13	8.05e-6	-5.303	Likely Benign	0.082	Likely Benign	Likely Benign										0.223	Likely Benign	-0.75	Neutral	0.007	Benign	0.004	Benign	3.77	Benign	0.00	Affected	4.32	4	0.2471	0.5502		1	0	-0.4	30.03
c.2888A>C	H963P 2D AIThe SynGAP1 missense variant H963P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only ESM1b predicts a pathogenic outcome, while the consensus score from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports benign, and the SGM Consensus also indicates Likely Benign; Foldetta data are not available. Overall, the majority of evidence points to a benign effect, and this conclusion is not in conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.991070	Disordered	0.983973	Binding	0.325	0.886	0.750											-8.158	Likely Pathogenic	0.074	Likely Benign	Likely Benign										0.223	Likely Benign	-1.10	Neutral	0.000	Benign	0.001	Benign	4.10	Benign	0.14	Tolerated			0.2101	0.4487		0	-2	1.6	-40.02
c.3158G>C	S1053T 2D AIThe SynGAP1 missense variant S1053T is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign impact for S1053T, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875											-6.209	Likely Benign	0.076	Likely Benign	Likely Benign										0.223	Likely Benign	-0.25	Neutral	0.625	Possibly Damaging	0.249	Benign	5.32	Benign	0.70	Tolerated			0.2055	0.5976		1	1	0.1	14.03
c.3353G>A	S1118N 2D AIThe SynGAP1 missense variant S1118N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods indicates that the variant is most likely benign, and this assessment is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750											-6.551	Likely Benign	0.102	Likely Benign	Likely Benign										0.223	Likely Benign	-0.53	Neutral	0.901	Possibly Damaging	0.433	Benign	5.26	Benign	0.06	Tolerated			0.1924	0.4215		1	1	-2.7	27.03
c.3399C>G	I1133M 2D AIThe SynGAP1 missense variant I1133M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this conclusion does not contradict any ClinVar annotation (none present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.832785	Binding	0.316	0.892	0.750											-3.409	Likely Benign	0.096	Likely Benign	Likely Benign										0.223	Likely Benign	-0.21	Neutral	0.016	Benign	0.009	Benign	5.45	Benign	0.06	Tolerated			0.0764	0.3685		2	1	-2.6	18.03
c.3875T>G	L1292R 2D AIThe SynGAP1 missense variant L1292R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, five tools predict pathogenicity while four predict benignity, giving a slight tilt toward a pathogenic interpretation. This prediction 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.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625											-4.249	Likely Benign	0.238	Likely Benign	Likely Benign										0.223	Likely Benign	-4.34	Deleterious	0.971	Probably Damaging	0.773	Possibly Damaging	2.46	Pathogenic	0.00	Affected			0.1286	0.0849		-3	-2	-8.3	43.03
c.549T>A	H183Q 2D AIThe SynGAP1 missense variant H183Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.383	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.223	Likely Benign	-5.43	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.88	Benign	0.01	Affected			0.1470	0.3623		3	0	-0.3	-9.01
c.549T>G	H183Q 2D AIThe SynGAP1 missense variant H183Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.476583	Structured	0.432952	Uncertain	0.421	0.622	0.500											-10.383	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic										0.223	Likely Benign	-5.43	Deleterious	0.838	Possibly Damaging	0.276	Benign	3.88	Benign	0.01	Affected			0.1470	0.3623		3	0	-0.3	-9.01
c.794A>G	K265R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K265R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster into two groups: benign predictions include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. No prediction or stability result is missing or inconclusive. Based on the aggregate evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-3.366	Likely Benign	0.136	Likely Benign	Likely Benign	0.04	Likely Benign	0.1	-0.44	Likely Benign	-0.20	Likely Benign	0.30	Likely Benign	0.223	Likely Benign	-1.08	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	1.90	Pathogenic	0.36	Tolerated			0.4713	0.0976		3	2	-0.6	28.01
c.146G>C	C49S 2D AIThe SynGAP1 missense variant C49S is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta results are unavailable. Overall, the majority of conventional tools (five pathogenic vs four benign) lean toward a pathogenic interpretation, but the single high‑accuracy benign prediction and the inconclusive SGM Consensus leave the assessment uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this 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.			0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000											-6.575	Likely Benign	0.704	Likely Pathogenic	Likely Benign										0.224	Likely Benign	-3.07	Deleterious	0.462	Possibly Damaging	0.478	Possibly Damaging	3.91	Benign	0.00	Affected			0.3855	0.1686		0	-1	-3.3	-16.06
c.1745A>G	E582G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E582G 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, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta give uncertain or inconclusive results. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, and Foldetta’s stability assessment is uncertain. Overall, six tools predict pathogenicity while five predict benign, and the high‑accuracy consensus is split. Thus, the variant is most likely pathogenic based on the preponderance of evidence, and this assessment 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	0.102787	Structured	0.033838	Uncertain	0.845	0.235	0.000											-9.621	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	1.35	Ambiguous	0.2	1.24	Ambiguous	1.30	Ambiguous	0.37	Likely Benign	0.224	Likely Benign	-3.95	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.13	Benign	0.13	Tolerated			0.2835	0.3325		0	-2	3.1	-72.06
c.1975T>C	S659P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S659P is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are SGM‑Consensus, Rosetta, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, premPS, and Foldetta—are treated as unavailable. High‑accuracy methods give mixed signals: AlphaMissense‑Optimized reports a benign change, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta’s stability assessment is uncertain. Overall, the balance of evidence leans toward a pathogenic effect, but the presence of a strong benign prediction from AlphaMissense‑Optimized and the lack of ClinVar annotation means the variant’s clinical significance remains uncertain and does not contradict existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.154597	Uncertain	0.954	0.283	0.000											-10.461	Likely Pathogenic	0.609	Likely Pathogenic	Likely Benign	-0.73	Ambiguous	0.3	2.98	Destabilizing	1.13	Ambiguous	0.73	Ambiguous	0.224	Likely Benign	-3.26	Deleterious	0.932	Possibly Damaging	0.245	Benign	3.39	Benign	0.18	Tolerated			0.2207	0.5553		1	-1	-0.8	10.04
c.2104C>A	Q702K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702K is not 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, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000											-8.750	Likely Pathogenic	0.338	Likely Benign	Likely Benign	-0.23	Likely Benign	0.0	0.26	Likely Benign	0.02	Likely Benign	0.08	Likely Benign	0.224	Likely Benign	-2.86	Deleterious	0.863	Possibly Damaging	0.773	Possibly Damaging	3.46	Benign	0.08	Tolerated			0.1346	0.2524		1	1	-0.4	0.04
c.2365C>A	P789T 2D AIThe SynGAP1 P789T missense variant has no ClinVar entry and is not present in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the variant’s likely effect: AlphaMissense‑Optimized predicts a benign outcome, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that P789T is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750											-5.242	Likely Benign	0.356	Ambiguous	Likely Benign										0.224	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.06	Pathogenic	0.00	Affected			0.1371	0.3837		0	-1	0.9	3.99
c.2617A>T	S873C 2D AIThe SynGAP1 missense variant S873C 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, FATHMM, and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a pathogenic view: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently contains no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.414856	Structured	0.649816	Binding	0.283	0.866	0.125											-8.293	Likely Pathogenic	0.502	Ambiguous	Likely Benign										0.224	Likely Benign	-2.71	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.62	Benign	0.04	Affected			0.1124	0.5887		0	-1	3.3	16.06
c.26A>C	H9P 2D AIThe SynGAP1 missense variant H9P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750											-2.838	Likely Benign	0.061	Likely Benign	Likely Benign										0.224	Likely Benign	-0.16	Neutral	0.107	Benign	0.006	Benign	4.19	Benign	0.00	Affected			0.2644	0.5169		0	-2	1.6	-40.02
c.274G>T	G92W 2D AIThe SynGAP1 missense variant G92W is not 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, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) suggest a pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.575842	Disordered	0.537848	Binding	0.337	0.874	0.625											-6.502	Likely Benign	0.789	Likely Pathogenic	Ambiguous										0.224	Likely Benign	-2.61	Deleterious	1.000	Probably Damaging	0.979	Probably Damaging	3.95	Benign	0.00	Affected			0.0640	0.4546		-7	-2	-0.5	129.16
c.3254G>A	R1085Q 2D AIThe SynGAP1 missense variant R1085Q (ClinVar ID 1729448.0) is listed as ClinVar status Uncertain and is present in gnomAD (6‑33443806‑G‑A). Functional prediction tools show a split opinion: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also favors benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, which is consistent with the ClinVar uncertain designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000					Uncertain		1	6-33443806-G-A	5	3.16e-6	-3.843	Likely Benign	0.589	Likely Pathogenic	Likely Benign										0.224	Likely Benign	-1.43	Neutral	0.998	Probably Damaging	0.988	Probably Damaging	2.73	Benign	0.02	Affected	3.77	5	0.2962	0.2751		1	1	1.0	-28.06
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.3575T>A	L1192Q 2D AIThe SynGAP1 missense variant L1192Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods points to a benign impact for this variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625											-3.804	Likely Benign	0.535	Ambiguous	Likely Benign										0.224	Likely Benign	-1.09	Neutral	0.992	Probably Damaging	0.940	Probably Damaging	2.70	Benign	0.10	Tolerated			0.1032	0.0558		-2	-2	-7.3	14.97
c.3881C>A	A1294D 2D AIThe SynGAP1 missense variant A1294D is listed in gnomAD (ID 6‑33447929‑C‑A) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessment further clarifies the picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward pathogenicity. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the lack of a benign ClinVar classification and the presence of the variant in a general population database. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.895011	Binding	0.565	0.806	0.625								6-33447929-C-A			-4.179	Likely Benign	0.369	Ambiguous	Likely Benign										0.224	Likely Benign	-4.17	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.14	Pathogenic	0.00	Affected	3.77	5	0.1893	0.2262		-2	0	-5.3	44.01
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.61T>G	F21V 2D AIThe SynGAP1 missense variant F21V is listed in gnomAD (ID 6‑33420325‑T‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.534167	Disordered	0.443284	Uncertain	0.369	0.897	0.500								6-33420325-T-G			-2.823	Likely Benign	0.563	Ambiguous	Likely Benign										0.224	Likely Benign	0.64	Neutral	0.462	Possibly Damaging	0.307	Benign	4.44	Benign	0.00	Affected	4.32	1	0.2536	0.2497		-1	-1	1.4	-48.04
c.902C>A	A301D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301D is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a predominance of benign calls: REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM all predict benign, whereas polyPhen‑2 (HumDiv and HumVar) and ESM1b predict pathogenic. Tools with uncertain outputs—Rosetta, Foldetta, and AlphaMissense‑Default—do not provide decisive evidence. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign verdict; Foldetta remains inconclusive. Taken together, the preponderance of evidence indicates that A301D is most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-10.276	Likely Pathogenic	0.488	Ambiguous	Likely Benign	-0.37	Likely Benign	0.2	-1.15	Ambiguous	-0.76	Ambiguous	0.23	Likely Benign	0.224	Likely Benign	-0.35	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.17	Benign	0.07	Tolerated			0.1599	0.1705		0	-2	-5.3	44.01
c.914C>T	T305I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T305I is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33437819‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, FoldX, premPS, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The high‑accuracy AlphaMissense‑Optimized score is benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports a benign effect. Overall, the balance of evidence from high‑confidence predictors leans toward a benign impact, and this assessment does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.359901	Structured	0.299706	Uncertain	0.872	0.274	0.125					Uncertain		1	6-33437819-C-T	1	6.20e-7	-5.222	Likely Benign	0.305	Likely Benign	Likely Benign	0.37	Likely Benign	0.2	0.58	Ambiguous	0.48	Likely Benign	0.25	Likely Benign	0.224	Likely Benign	-2.90	Deleterious	0.997	Probably Damaging	0.929	Probably Damaging	1.70	Pathogenic	0.04	Affected	3.40	20	0.0939	0.5693		-1	0	5.2	12.05
c.1300G>C	V434L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools, Rosetta and AlphaMissense‑Default, give uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta, a protein‑folding stability method, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that V434L is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000											-8.697	Likely Pathogenic	0.477	Ambiguous	Likely Benign	-0.05	Likely Benign	0.0	1.02	Ambiguous	0.49	Likely Benign	0.20	Likely Benign	0.225	Likely Benign	-2.30	Neutral	0.947	Possibly Damaging	0.851	Possibly Damaging	3.64	Benign	0.27	Tolerated			0.0895	0.3813		2	1	-0.4	14.03
c.2120C>A	A707D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A707D is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools give uncertain results: premPS and Rosetta. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000											-9.160	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign	0.29	Likely Benign	0.0	-0.61	Ambiguous	-0.16	Likely Benign	0.89	Ambiguous	0.225	Likely Benign	-3.16	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.39	Benign	0.02	Affected			0.1376	0.1741		0	-2	-5.3	44.01
c.2137C>A	P713T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and FATHMM, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further clarify the picture: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic, whereas AlphaMissense‑Optimized and Foldetta provide inconclusive results and are treated as unavailable. Taken together, the preponderance of evidence points to a pathogenic effect for P713T, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-9.915	Likely Pathogenic	0.819	Likely Pathogenic	Ambiguous	1.15	Ambiguous	0.0	0.46	Likely Benign	0.81	Ambiguous	0.65	Ambiguous	0.225	Likely Benign	-6.72	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.34	Benign	0.00	Affected			0.1417	0.3818		0	-1	0.9	3.99
c.2163C>G	I721M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant I721M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, premPS, and the SGM‑Consensus score (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No prediction or stability result is missing or inconclusive beyond these stated uncertainties. Overall, the preponderance of evidence points to a pathogenic effect for I721M, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.394753	Structured	0.454550	Uncertain	0.957	0.437	0.125											-9.767	Likely Pathogenic	0.872	Likely Pathogenic	Ambiguous	0.71	Ambiguous	0.0	0.45	Likely Benign	0.58	Ambiguous	1.00	Destabilizing	0.225	Likely Benign	-2.40	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	2.30	Pathogenic	0.00	Affected			0.0576	0.2726		2	1	-2.6	18.03
c.2485G>C	E829Q 2D AIThe SynGAP1 missense variant E829Q is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of reliable tools predict a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375											-4.985	Likely Benign	0.531	Ambiguous	Likely Benign										0.225	Likely Benign	-1.83	Neutral	0.994	Probably Damaging	0.946	Probably Damaging	2.26	Pathogenic	0.00	Affected			0.1321	0.7248		2	2	0.0	-0.98
c.3157A>C	S1053R 2D AIThe SynGAP1 missense variant S1053R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority‑vote SGM‑Consensus also reports a likely benign outcome. In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy analyses reinforce the benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely benign, with no contradictory Foldetta data. Overall, the preponderance of evidence points to a benign effect for S1053R, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875											-6.421	Likely Benign	0.359	Ambiguous	Likely Benign										0.225	Likely Benign	0.43	Neutral	0.969	Probably Damaging	0.581	Possibly Damaging	5.33	Benign	0.59	Tolerated	3.77	5	0.1321	0.3820		-1	0	-3.7	69.11
c.3227T>C	L1076S 2D AIThe SynGAP1 missense variant L1076S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and ESM1b, whereas polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default all predict a pathogenic outcome. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic votes); and Foldetta results are unavailable. Consequently, the evidence is evenly split between benign and pathogenic predictions. The variant is therefore most likely of uncertain significance, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.922952	Disordered	0.989617	Binding	0.301	0.892	0.750											-2.975	Likely Benign	0.913	Likely Pathogenic	Ambiguous										0.225	Likely Benign	0.55	Neutral	0.999	Probably Damaging	0.983	Probably Damaging	2.43	Pathogenic	0.75	Tolerated			0.3045	0.1178		-3	-2	-4.6	-26.08
c.325A>C	S109R 2D AIThe SynGAP1 missense variant S109R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM, whereas pathogenic calls come from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments highlight that AlphaMissense‑Optimized predicts pathogenicity, whereas the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts benign impact; Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign effect for S109R, 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		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-4.830	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.225	Likely Benign	-1.80	Neutral	0.002	Benign	0.001	Benign	3.48	Benign	0.00	Affected			0.0884	0.2700		0	-1	-3.7	69.11
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.3920C>G	P1307R 2D AIThe SynGAP1 missense variant P1307R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the available predictions indicates that P1307R is most likely benign, and this assessment does not conflict with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.798249	Disordered	0.913511	Binding	0.491	0.901	0.875											-4.022	Likely Benign	0.183	Likely Benign	Likely Benign										0.225	Likely Benign	-1.17	Neutral	0.887	Possibly Damaging	0.664	Possibly Damaging	2.82	Benign	0.06	Tolerated			0.1552	0.2763		0	-2	-2.9	59.07
c.538T>C	S180P 2D AIThe SynGAP1 missense variant S180P is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500											-14.574	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic										0.225	Likely Benign	-3.19	Deleterious	0.917	Possibly Damaging	0.446	Benign	3.81	Benign	0.01	Affected			0.1916	0.4735		1	-1	-0.8	10.04
c.818A>G	E273G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E273G missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, premPS, SIFT, and ESM1b; pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Four tools (FoldX, Rosetta, AlphaMissense‑Default, Foldetta) returned uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic; Foldetta remains uncertain. Given the split between benign and pathogenic signals and the lack of a ClinVar classification, the variant is best described as of uncertain significance, with a slight inclination toward benign based on the most reliable single‑tool prediction. This assessment does not contradict any existing ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.071867	Structured	0.398918	Uncertain	0.863	0.196	0.125											-4.784	Likely Benign	0.373	Ambiguous	Likely Benign	-0.65	Ambiguous	0.2	-0.93	Ambiguous	-0.79	Ambiguous	-0.46	Likely Benign	0.225	Likely Benign	-2.71	Deleterious	0.896	Possibly Damaging	0.519	Possibly Damaging	1.95	Pathogenic	0.26	Tolerated			0.2763	0.3341		0	-2	3.1	-72.06
c.901G>C	A301P 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301P is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375											-3.808	Likely Benign	0.085	Likely Benign	Likely Benign	-0.47	Likely Benign	0.1	-0.41	Likely Benign	-0.44	Likely Benign	0.40	Likely Benign	0.225	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.11	Benign	0.06	Tolerated			0.1907	0.5371		1	-1	-3.4	26.04
c.1309C>T	P437S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P437S is not reported in ClinVar (ClinVar ID: None) but is present in gnomAD (ID 6‑33438214‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b all predict a pathogenic outcome; the remaining methods (FoldX, Foldetta, premPS, AlphaMissense‑Default) are uncertain and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic interpretation. 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.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000								6-33438214-C-T	2	1.24e-6	-11.964	Likely Pathogenic	0.518	Ambiguous	Likely Benign	1.14	Ambiguous	0.0	-3.31	Stabilizing	-1.09	Ambiguous	0.60	Ambiguous	0.226	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.49	Benign	0.01	Affected	3.38	26	0.3548	0.4843		-1	1	0.8	-10.04
c.2450C>T	S817L 2D AIThe SynGAP1 missense variant S817L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625											-7.612	In-Between	0.659	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-3.90	Deleterious	0.997	Probably Damaging	0.945	Probably Damaging	2.41	Pathogenic	0.00	Affected			0.1226	0.5662		-3	-2	4.6	26.08
c.2776T>A	S926T 2D AIThe SynGAP1 missense variant S926T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) is inconclusive, with two pathogenic and two benign votes. AlphaMissense‑Optimized, a high‑accuracy model, predicts benign, while Foldetta stability analysis is unavailable. Overall, the majority of standard tools favor a pathogenic effect, whereas the single high‑accuracy model suggests benign. Thus, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.461924	Structured	0.981753	Binding	0.295	0.854	0.250											-2.917	Likely Benign	0.651	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-2.34	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.55	Pathogenic	0.00	Affected			0.1174	0.5663		1	1	0.1	14.03
c.3062A>T	Q1021L 2D AIThe SynGAP1 missense variant Q1021L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500											-5.780	Likely Benign	0.678	Likely Pathogenic	Likely Benign										0.226	Likely Benign	-3.36	Deleterious	0.985	Probably Damaging	0.982	Probably Damaging	2.58	Benign	0.01	Affected			0.0688	0.5039		-2	-2	7.3	-14.97
c.3652G>C	E1218Q 2D AIThe SynGAP1 E1218Q missense change 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 ESM1b, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie and thus inconclusive; Foldetta results are not available. Consequently, the majority of conventional predictors lean toward pathogenicity, but the most reliable tools do not provide a clear verdict. The variant is therefore most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.595080	Disordered	0.483050	Uncertain	0.898	0.565	0.375											-6.490	Likely Benign	0.857	Likely Pathogenic	Ambiguous										0.226	Likely Benign	-2.09	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.32	Pathogenic	0.00	Affected			0.0784	0.3666		2	2	0.0	-0.98
c.3664A>G	R1222G 2D AIThe SynGAP1 missense change R1222G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools split into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) also indicates likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-11.498	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic										0.226	Likely Benign	-5.41	Deleterious	0.997	Probably Damaging	0.994	Probably Damaging	1.48	Pathogenic	0.10	Tolerated			0.3012	0.2305		-3	-2	4.1	-99.14
c.1118G>C	G373A 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G373A is not reported in ClinVar and is absent from gnomAD. Functional prediction consensus shows a predominance of benign calls: REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict a benign effect. Pathogenic predictions are limited to SIFT and FoldX, while Rosetta and Foldetta yield uncertain results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta remains inconclusive. Overall, the majority of evidence indicates that G373A is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.529623	Disordered	0.429267	Uncertain	0.295	0.799	0.625											-5.181	Likely Benign	0.099	Likely Benign	Likely Benign	2.44	Destabilizing	0.8	0.69	Ambiguous	1.57	Ambiguous	-0.01	Likely Benign	0.227	Likely Benign	-0.47	Neutral	0.000	Benign	0.000	Benign	3.93	Benign	0.01	Affected			0.4172	0.5053		1	0	2.2	14.03
c.1131G>A	M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I (ClinVar ID 3803473.0, status = Uncertain) is present in gnomAD (ID = 6‑33438036‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” while Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the computational evidence strongly favors a benign classification, which does not contradict the ClinVar status of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.675549	Disordered	0.431183	Uncertain	0.324	0.884	0.625					Uncertain		1	6-33438036-G-A	1	6.23e-7	-2.895	Likely Benign	0.212	Likely Benign	Likely Benign	0.76	Ambiguous	0.3	0.54	Ambiguous	0.65	Ambiguous	0.24	Likely Benign	0.227	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	5.46	Benign	0.26	Tolerated	4.32	12	0.2240	0.4133		1	2	2.6	-18.03
c.1131G>C	M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus classify the change as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is therefore not considered evidence for pathogenicity. Overall, the collective evidence points to a benign impact for M377I, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.675549	Disordered	0.431183	Uncertain	0.324	0.884	0.625											-2.895	Likely Benign	0.212	Likely Benign	Likely Benign	0.76	Ambiguous	0.3	0.54	Ambiguous	0.65	Ambiguous	0.24	Likely Benign	0.227	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	5.46	Benign	0.26	Tolerated	4.32	12	0.2240	0.4133		1	2	2.6	-18.03
c.1131G>T	M377I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M377I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus classify the change as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is therefore not considered evidence for pathogenicity. Overall, the evidence overwhelmingly supports a benign interpretation, 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 Benign	C2	0.675549	Disordered	0.431183	Uncertain	0.324	0.884	0.625											-2.895	Likely Benign	0.212	Likely Benign	Likely Benign	0.76	Ambiguous	0.3	0.54	Ambiguous	0.65	Ambiguous	0.24	Likely Benign	0.227	Likely Benign	-0.41	Neutral	0.000	Benign	0.001	Benign	5.46	Benign	0.26	Tolerated	4.32	12	0.2240	0.4133		1	2	2.6	-18.03
c.1210G>C	A404P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A404P is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, both polyPhen‑2 versions, and FATHMM, while pathogenic calls arise from FoldX, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus confirms likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.232838	Structured	0.415505	Uncertain	0.965	0.355	0.000											-11.819	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	3.03	Destabilizing	0.1	0.24	Likely Benign	1.64	Ambiguous	1.17	Destabilizing	0.227	Likely Benign	-3.16	Deleterious	0.433	Benign	0.080	Benign	4.02	Benign	0.03	Affected			0.2271	0.6366		1	-1	-3.4	26.04
c.1563G>C	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change E521D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as Benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a Benign effect. No prediction or stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1563G>T	E521D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E521D missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools—polyPhen‑2 HumDiv and HumVar—predict a pathogenic outcome. The high‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.086953	Structured	0.062387	Uncertain	0.865	0.349	0.000											-4.963	Likely Benign	0.372	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.17	Likely Benign	0.15	Likely Benign	-0.29	Likely Benign	0.227	Likely Benign	1.07	Neutral	0.986	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.92	Tolerated			0.2026	0.3721		3	2	0.0	-14.03
c.1993T>G	Y665D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y665D is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as Uncertain. No evidence from these tools contradicts the ClinVar status, which is currently unreported. Overall, the balance of evidence—seven pathogenic versus four benign predictions, with a pathogenic consensus from SGM‑Consensus—suggests the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.098513	Structured	0.086641	Uncertain	0.922	0.361	0.000											-10.101	Likely Pathogenic	0.737	Likely Pathogenic	Likely Benign	1.15	Ambiguous	0.2	1.30	Ambiguous	1.23	Ambiguous	0.15	Likely Benign	0.227	Likely Benign	-3.67	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.75	Benign	1.00	Tolerated			0.3838	0.0573		-4	-3	-2.2	-48.09
c.2330T>G	L777R 2D AIThe SynGAP1 missense variant L777R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-6.084	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.227	Likely Benign	-2.20	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.97	Benign	0.00	Affected			0.1249	0.0846		-3	-2	-8.3	43.03
c.2489C>G	P830R 2D AIThe SynGAP1 missense variant P830R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of reliable predictors and the high‑accuracy consensus indicate a benign 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.			0.590140	Disordered	0.618152	Binding	0.333	0.874	0.500											-5.919	Likely Benign	0.515	Ambiguous	Likely Benign										0.227	Likely Benign	-3.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.72	Benign	0.00	Affected			0.1277	0.2984		0	-2	-2.9	59.07
c.3430T>G	L1144V 2D AIThe SynGAP1 missense variant L1144V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.726803	Binding	0.277	0.840	1.000											-4.025	Likely Benign	0.151	Likely Benign	Likely Benign										0.227	Likely Benign	-0.04	Neutral	0.952	Possibly Damaging	0.770	Possibly Damaging	5.43	Benign	0.70	Tolerated			0.1553	0.3297		2	1	0.4	-14.03
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.3516C>A	H1172Q 2D AIThe SynGAP1 missense variant H1172Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus confirms Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.673805	Binding	0.465	0.758	0.625											-2.169	Likely Benign	0.414	Ambiguous	Likely Benign										0.227	Likely Benign	-0.51	Neutral	0.451	Benign	0.265	Benign	5.47	Benign	0.39	Tolerated			0.1249	0.3557		3	0	-0.3	-9.01
c.3516C>G	H1172Q 2D AIThe SynGAP1 missense variant H1172Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus confirms Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Based on the collective predictions, H1172Q is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.673805	Binding	0.465	0.758	0.625											-2.169	Likely Benign	0.414	Ambiguous	Likely Benign										0.227	Likely Benign	-0.51	Neutral	0.451	Benign	0.265	Benign	5.47	Benign	0.39	Tolerated			0.1249	0.3557		3	0	-0.3	-9.01
c.3772C>A	Q1258K 2D AIThe SynGAP1 missense variant Q1258K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas the majority of other in silico predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—classify it as pathogenic. Grouping by consensus, the benign prediction is represented only by REVEL, while the pathogenic predictions are supported by seven distinct algorithms. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized returns an uncertain result, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels the variant as likely pathogenic, and Foldetta data are not available. Taken together, the preponderance of evidence from multiple pathogenic predictors and the SGM‑Consensus suggests that the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Thus, the variant is most likely pathogenic, and this prediction does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.486429	Structured	0.525814	Binding	0.859	0.577	0.250											-10.927	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous										0.227	Likely Benign	-3.19	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	2.03	Pathogenic	0.00	Affected			0.1151	0.2761		1	1	-0.4	0.04
c.3777C>G	I1259M 2D AIThe SynGAP1 missense variant I1259M is catalogued in gnomAD (ID 6‑33446769‑C‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score, whereas PolyPhen‑2 (HumDiv and HumVar) classify the change as pathogenic. The high‑accuracy AlphaMissense‑Optimized tool reports a benign effect, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign. Foldetta, a protein‑folding stability method that integrates 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 is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.494003	Structured	0.576405	Binding	0.885	0.574	0.250								6-33446769-C-G	2	1.24e-6	-5.177	Likely Benign	0.447	Ambiguous	Likely Benign										0.227	Likely Benign	1.35	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.87	Benign	1.00	Tolerated	3.77	5	0.0576	0.2358		1	2	-2.6	18.03
c.3863A>C	K1288T 2D AIThe SynGAP1 missense variant K1288T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy consensus also leans pathogenic. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-2.616	Likely Benign	0.477	Ambiguous	Likely Benign										0.227	Likely Benign	-4.84	Deleterious	0.991	Probably Damaging	0.982	Probably Damaging	2.09	Pathogenic	0.00	Affected			0.2066	0.2614		0	-1	3.2	-27.07
c.3G>A	M1I 2D AIThe SynGAP1 missense variant M1I is listed in ClinVar (ID 833646.0) with an uncertain significance annotation and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM all classify the substitution as benign, while SIFT uniquely predicts it to be pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy predictors are incomplete: AlphaMissense‑Optimized and the Foldetta stability assessment are unavailable for this variant. Taking the collective evidence into account, the variant is most likely benign, and this assessment does not conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.540766	Binding	0.354	0.924	0.875					Conflicting		3				-5.397	Likely Benign													0.227	Likely Benign	-0.17	Neutral	0.001	Benign	0.000	Benign	4.25	Benign	0.00	Affected	4.32	1	0.1655	0.4008		2	1	2.6	-18.03
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.515G>C	R172P 2D AIThe SynGAP1 missense variant R172P has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, while Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.525368	Disordered	0.491688	Uncertain	0.411	0.651	0.375											-8.059	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous										0.227	Likely Benign	-3.16	Deleterious	0.929	Possibly Damaging	0.519	Possibly Damaging	3.99	Benign	0.01	Affected			0.1864	0.4312		0	-2	2.9	-59.07
c.545C>T	S182F 2D AIThe SynGAP1 missense variant S182F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as likely pathogenic, and the Foldetta stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the corroborating high‑accuracy tools, the variant is most likely pathogenic, with no conflict with ClinVar status (which is absent). 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											-12.027	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.227	Likely Benign	-4.30	Deleterious	0.838	Possibly Damaging	0.466	Possibly Damaging	3.64	Benign	0.00	Affected			0.0597	0.5482		-3	-2	3.6	60.10
c.967C>G	L323V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L323V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, premPS, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic predictions (FoldX, Rosetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Benign. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates Likely Benign; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.268042	Structured	0.428564	Uncertain	0.956	0.369	0.000											-3.483	Likely Benign	0.107	Likely Benign	Likely Benign	2.18	Destabilizing	0.3	2.22	Destabilizing	2.20	Destabilizing	0.17	Likely Benign	0.227	Likely Benign	0.19	Neutral	0.898	Possibly Damaging	0.472	Possibly Damaging	0.80	Pathogenic	0.80	Tolerated			0.1277	0.2656		2	1	0.4	-14.03
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.1435C>G	R479G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R479G is reported in gnomAD (ID 6-33438467-C-G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, Rosetta, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). FoldX and Foldetta, which assess protein‑folding stability, returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta as inconclusive. Overall, the majority of computational evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Therefore, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000								6-33438467-C-G	1	6.20e-7	-8.600	Likely Pathogenic	0.624	Likely Pathogenic	Likely Benign	0.97	Ambiguous	0.0	2.51	Destabilizing	1.74	Ambiguous	0.71	Ambiguous	0.228	Likely Benign	-2.82	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.42	Tolerated	3.39	32	0.2911	0.2707		-2	-3	4.1	-99.14