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.1009A>C	K337Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K337Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate 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	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-9.944	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.00	Likely Benign	0.0	0.88	Ambiguous	0.44	Likely Benign	0.43	Likely Benign	0.305	Likely Benign	-3.48	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.70	Pathogenic	0.01	Affected			0.3672	0.1219		1	1	0.4	-0.04
c.1009A>G	K337E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K337E missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic impact comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The premPS score is uncertain and does not influence the overall assessment. High‑accuracy analyses show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as benign. Based on the majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.673	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	-0.05	Likely Benign	0.1	0.49	Likely Benign	0.22	Likely Benign	0.52	Ambiguous	0.316	Likely Benign	-3.48	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	1.76	Pathogenic	0.02	Affected			0.3102	0.1039		0	1	0.4	0.94
c.1011G>C	K337N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337N 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, Rosetta, premPS, and SIFT. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (seven pathogenic vs. five benign) and the high‑accuracy consensus lean toward a pathogenic impact. Thus, 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	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.1	0.36	Likely Benign	0.24	Likely Benign	-0.02	Likely Benign	0.280	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.87	Pathogenic	0.11	Tolerated			0.2945	0.1315		1	0	0.4	-14.07
c.1011G>T	K337N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K337N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With seven tools supporting pathogenicity versus five supporting benign, the overall prediction leans toward pathogenic. No ClinVar entry contradicts this assessment, and the variant is absent from gnomAD, so the pathogenic prediction is not challenged by population data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.348540	Uncertain	0.449	0.438	0.500											-13.095	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.12	Likely Benign	0.1	0.36	Likely Benign	0.24	Likely Benign	-0.02	Likely Benign	0.280	Likely Benign	-4.38	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.87	Pathogenic	0.11	Tolerated			0.2945	0.1315		1	0	0.4	-14.07
c.1015A>C	K339Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evaluated tools (8 pathogenic vs. 4 benign) indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-10.952	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	0.06	Likely Benign	0.0	-0.50	Ambiguous	-0.22	Likely Benign	-0.02	Likely Benign	0.458	Likely Benign	-3.06	Deleterious	0.982	Probably Damaging	0.824	Possibly Damaging	1.90	Pathogenic	0.04	Affected			0.4041	0.1012		1	1	0.4	-0.04
c.1015A>G	K339E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-14.284	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.13	Likely Benign	0.1	-0.03	Likely Benign	0.05	Likely Benign	0.40	Likely Benign	0.482	Likely Benign	-3.00	Deleterious	0.939	Possibly Damaging	0.670	Possibly Damaging	1.92	Pathogenic	0.03	Affected			0.3421	0.0882		0	1	0.4	0.94
c.1017G>C	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K339N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect include PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the majority of evidence points to a pathogenic impact for K339N, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1017G>T	K339N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K339N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect. Overall, the majority of evidence points toward a pathogenic impact for K339N, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.447574	Structured	0.384153	Uncertain	0.535	0.465	0.250											-11.117	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.20	Likely Benign	0.0	0.35	Likely Benign	0.28	Likely Benign	0.00	Likely Benign	0.410	Likely Benign	-3.88	Deleterious	0.991	Probably Damaging	0.864	Possibly Damaging	1.91	Pathogenic	0.02	Affected			0.3224	0.1158		1	0	0.4	-14.07
c.1033C>G	L345V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L345V missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, Rosetta, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans toward benign. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.260850	Structured	0.354989	Uncertain	0.936	0.478	0.125											-6.594	Likely Benign	0.131	Likely Benign	Likely Benign	1.31	Ambiguous	0.0	0.18	Likely Benign	0.75	Ambiguous	0.92	Ambiguous	0.126	Likely Benign	-1.96	Neutral	0.802	Possibly Damaging	0.277	Benign	1.77	Pathogenic	0.06	Tolerated			0.1411	0.3455		2	1	0.4	-14.03
c.1057C>G	L353V 2D AISynGAP1 missense variant L353V is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools predicting pathogenicity are FoldX and FATHMM, while Rosetta gives an uncertain result. 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 benign, SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the balance of evidence favors a benign effect; this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000											-2.100	Likely Benign	0.078	Likely Benign	Likely Benign	3.08	Destabilizing	0.9	1.48	Ambiguous	2.28	Destabilizing	-0.45	Likely Benign	0.074	Likely Benign	1.54	Neutral	0.002	Benign	0.002	Benign	1.46	Pathogenic	0.89	Tolerated			0.1567	0.3829		2	1	0.4	-14.03
c.1099C>G	L367V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L367V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include 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, and PROVEAN). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta) are inconclusive, so they provide no evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the preponderance of evidence points to a benign effect for L367V, 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	0.370445	Structured	0.441805	Uncertain	0.790	0.657	0.250											-2.383	Likely Benign	0.066	Likely Benign	Likely Benign	1.48	Ambiguous	0.2	1.72	Ambiguous	1.60	Ambiguous	0.15	Likely Benign	0.040	Likely Benign	0.19	Neutral	0.410	Benign	0.104	Benign	1.67	Pathogenic	0.13	Tolerated			0.2321	0.3285		2	1	0.4	-14.03
c.1111A>G	S371G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S371G is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined—REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized—classifies the substitution as benign. No pathogenic predictions are present. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375											-2.073	Likely Benign	0.053	Likely Benign	Likely Benign	0.47	Likely Benign	0.3	0.49	Likely Benign	0.48	Likely Benign	0.35	Likely Benign	0.164	Likely Benign	-1.32	Neutral	0.213	Benign	0.067	Benign	4.63	Benign	0.17	Tolerated			0.3192	0.5295		1	0	0.4	-30.03
c.1174A>C	K392Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K392Q has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL and polyPhen‑2 HumDiv. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.541878	Disordered	0.405672	Uncertain	0.319	0.702	0.750											-4.243	Likely Benign	0.377	Ambiguous	Likely Benign	0.13	Likely Benign	0.0	0.05	Likely Benign	0.09	Likely Benign	0.23	Likely Benign	0.525	Likely Pathogenic	-2.09	Neutral	0.652	Possibly Damaging	0.161	Benign	4.61	Benign	0.06	Tolerated			0.5612	0.2106	Weaken	1	1	0.4	-0.04
c.1174A>G	K392E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K392E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score. Tools that predict a pathogenic effect are REVEL, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, while the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both indicate a benign outcome. Overall, the majority of evidence supports a benign classification, 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	C2	0.541878	Disordered	0.405672	Uncertain	0.319	0.702	0.750											-4.392	Likely Benign	0.850	Likely Pathogenic	Ambiguous	0.09	Likely Benign	0.0	-0.04	Likely Benign	0.03	Likely Benign	0.28	Likely Benign	0.529	Likely Pathogenic	-1.92	Neutral	0.276	Benign	0.083	Benign	4.60	Benign	0.02	Affected			0.4812	0.1916		0	1	0.4	0.94
c.1176G>C	K392N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K392N 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, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of evidence (9 benign vs 3 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.		C2	0.541878	Disordered	0.405672	Uncertain	0.319	0.702	0.750											-4.136	Likely Benign	0.780	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.1	-0.01	Likely Benign	0.12	Likely Benign	0.20	Likely Benign	0.229	Likely Benign	-2.61	Deleterious	0.276	Benign	0.083	Benign	4.60	Benign	0.02	Affected			0.4586	0.2454		1	0	0.4	-14.07
c.1176G>T	K392N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K392N is not 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, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split and is therefore treated as unavailable. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, predicts a benign effect. Overall, the majority of evidence (nine benign vs. three pathogenic predictions) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.541878	Disordered	0.405672	Uncertain	0.319	0.702	0.750											-4.136	Likely Benign	0.780	Likely Pathogenic	Likely Benign	0.24	Likely Benign	0.1	-0.01	Likely Benign	0.12	Likely Benign	0.20	Likely Benign	0.229	Likely Benign	-2.61	Deleterious	0.276	Benign	0.083	Benign	4.60	Benign	0.02	Affected			0.4586	0.2454		1	0	0.4	-14.07
c.1180A>C	K394Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K394Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic outcome are SIFT and Rosetta. The remaining tools—Foldetta, premPS, ESM1b, and AlphaMissense‑Default—return 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 AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also leans toward benign, with two benign votes and two uncertain votes. Foldetta’s stability prediction is uncertain and thus not considered. Overall, the majority of reliable predictions indicate a benign effect, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625											-7.261	In-Between	0.468	Ambiguous	Likely Benign	0.15	Likely Benign	0.0	2.00	Destabilizing	1.08	Ambiguous	0.64	Ambiguous	0.330	Likely Benign	-2.46	Neutral	0.001	Benign	0.009	Benign	4.61	Benign	0.01	Affected			0.5365	0.2106	Weaken	1	1	0.4	-0.04
c.1180A>G	K394E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K394E is not listed in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438085‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Those that predict a pathogenic effect are premPS, PROVEAN, SIFT, and AlphaMissense‑Default. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. No prediction or folding‑stability result is available that decisively supports either outcome. Overall, the majority of tools (six benign vs four pathogenic) lean toward a benign interpretation, and this assessment does not contradict the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625								6-33438085-A-G	1	6.20e-7	-6.903	Likely Benign	0.896	Likely Pathogenic	Ambiguous	0.07	Likely Benign	0.1	3.71	Destabilizing	1.89	Ambiguous	1.20	Destabilizing	0.446	Likely Benign	-2.54	Deleterious	0.063	Benign	0.038	Benign	4.61	Benign	0.04	Affected	3.44	14	0.4556	0.1916		1	0	0.4	0.94
c.1182A>C	K394N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K394N 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, FATHMM, and polyPhen‑2 HumVar. Those that agree on a pathogenic effect are Rosetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are Foldetta, premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, Foldetta as uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625											-7.408	In-Between	0.861	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.1	2.02	Destabilizing	1.05	Ambiguous	0.66	Ambiguous	0.299	Likely Benign	-3.17	Deleterious	0.535	Possibly Damaging	0.188	Benign	4.60	Benign	0.01	Affected			0.4353	0.2654		1	0	0.4	-14.07
c.1182A>T	K394N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K394N missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, FoldX, FATHMM, and polyPhen‑2 HumVar, while pathogenic calls come from Rosetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Four tools (Foldetta, premPS, ESM1b, AlphaMissense‑Optimized) return uncertain results. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves as pathogenic; and Foldetta is uncertain. Taken together, the majority of evidence—including the high‑accuracy consensus—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.		C2	0.505461	Disordered	0.399336	Uncertain	0.387	0.634	0.625											-7.408	In-Between	0.861	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.1	2.02	Destabilizing	1.05	Ambiguous	0.66	Ambiguous	0.299	Likely Benign	-3.17	Deleterious	0.535	Possibly Damaging	0.188	Benign	4.60	Benign	0.01	Affected			0.4353	0.2654		1	0	0.4	-14.07
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.1207A>C	K403Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. In contrast, a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. The premPS assessment is uncertain and does not influence the overall consensus. High‑accuracy analyses show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-12.479	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.36	Likely Benign	0.0	0.27	Likely Benign	0.32	Likely Benign	0.70	Ambiguous	0.376	Likely Benign	-3.59	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	3.76	Benign	0.01	Affected			0.4405	0.1954		1	1	0.4	-0.04
c.1207A>G	K403E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K403E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and FATHMM. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions from FoldX, Rosetta, Foldetta, and premPS are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for K403E, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000											-15.279	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.01	Ambiguous	0.1	0.79	Ambiguous	0.90	Ambiguous	0.70	Ambiguous	0.445	Likely Benign	-3.62	Deleterious	0.998	Probably Damaging	0.981	Probably Damaging	3.79	Benign	0.04	Affected			0.3650	0.1715		0	1	0.4	0.94
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.1228A>G	S410G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S410G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000											-7.147	In-Between	0.137	Likely Benign	Likely Benign	0.58	Ambiguous	0.1	1.33	Ambiguous	0.96	Ambiguous	0.85	Ambiguous	0.117	Likely Benign	-2.54	Deleterious	0.952	Possibly Damaging	0.145	Benign	4.13	Benign	0.19	Tolerated			0.2651	0.5143		1	0	0.4	-30.03
c.1234T>G	L412V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L412V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000											-11.726	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	3.65	Destabilizing	0.0	3.52	Destabilizing	3.59	Destabilizing	1.54	Destabilizing	0.231	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.25	Benign	0.01	Affected			0.1275	0.3378		2	1	0.4	-14.03
c.1246C>G	L416V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for the variant. This conclusion is not contradicted by any ClinVar annotation, as the variant is not present in that database. 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											-7.861	In-Between	0.310	Likely Benign	Likely Benign	1.46	Ambiguous	0.0	1.78	Ambiguous	1.62	Ambiguous	0.45	Likely Benign	0.124	Likely Benign	-1.47	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.42	Benign	0.53	Tolerated			0.1563	0.3550		2	1	0.4	-14.03
c.1252A>C	K418Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K418Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-11.404	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.10	Likely Benign	0.1	0.17	Likely Benign	0.14	Likely Benign	0.30	Likely Benign	0.263	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.55	Benign	0.13	Tolerated			0.4105	0.0696		1	1	0.4	-0.04
c.1252A>G	K418E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418E 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, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evaluated tools (seven pathogenic vs four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for K418E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-12.443	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.80	Ambiguous	0.72	Ambiguous	0.47	Likely Benign	0.367	Likely Benign	-3.42	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.53	Benign	0.07	Tolerated			0.3578	0.0471		0	1	0.4	0.94
c.1254A>C	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM. The majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS, Foldetta) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that K418N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1254A>T	K418N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two consensus groups: benign predictions are provided by REVEL and FATHMM, whereas pathogenic predictions are given by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus score (Likely Pathogenic). Stability‑based methods FoldX, Rosetta, Foldetta, and premPS returned uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, and Foldetta’s stability analysis is inconclusive. Overall, the majority of reliable predictors classify K418N as pathogenic, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000											-13.310	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.57	Ambiguous	0.0	0.77	Ambiguous	0.67	Ambiguous	0.56	Ambiguous	0.132	Likely Benign	-4.41	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.04	Affected			0.3483	0.0606		1	0	0.4	-14.07
c.1291C>G	L431V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L431V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are FoldX, premPS, PROVEAN, and polyPhen‑2 HumDiv. Four tools (Rosetta, Foldetta, ESM1b, AlphaMissense‑Default) give uncertain or inconclusive results. 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 1‑to‑1 split between benign and pathogenic signals, and Foldetta also yields an uncertain outcome. Overall, the balance of evidence—including the higher number of benign predictions and the benign call from the most accurate tool—suggests that the variant is most likely benign. 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	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000											-7.949	In-Between	0.505	Ambiguous	Likely Benign	2.17	Destabilizing	0.0	1.50	Ambiguous	1.84	Ambiguous	1.32	Destabilizing	0.093	Likely Benign	-2.58	Deleterious	0.861	Possibly Damaging	0.332	Benign	3.04	Benign	0.20	Tolerated			0.1377	0.3198		2	1	0.4	-14.03
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.1315C>G	L439V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; premPS is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of predictions (8 benign vs. 5 pathogenic) favor a benign classification, and this consensus does not contradict the absence of ClinVar evidence. Thus, based on current computational predictions, the variant is most likely benign. 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											-6.340	Likely Benign	0.279	Likely Benign	Likely Benign	2.34	Destabilizing	0.2	2.40	Destabilizing	2.37	Destabilizing	0.91	Ambiguous	0.121	Likely Benign	-1.13	Neutral	0.976	Probably Damaging	0.941	Probably Damaging	3.36	Benign	0.12	Tolerated			0.1272	0.2628		2	1	0.4	-14.03
c.1324A>C	K442Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K442Q is not 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 PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, 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) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. 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.		GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-10.410	Likely Pathogenic	0.562	Ambiguous	Likely Benign	0.05	Likely Benign	0.1	0.03	Likely Benign	0.04	Likely Benign	0.25	Likely Benign	0.268	Likely Benign	-3.10	Deleterious	0.998	Probably Damaging	0.995	Probably Damaging	3.39	Benign	0.18	Tolerated			0.3353	0.1014		1	1	0.4	-0.04
c.1324A>G	K442E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split consensus: benign predictions come from REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized remains uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No single evidence decisively outweighs the others. Therefore, the variant’s pathogenicity remains uncertain; the predictions do not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-12.813	Likely Pathogenic	0.939	Likely Pathogenic	Ambiguous	-0.05	Likely Benign	0.1	-0.21	Likely Benign	-0.13	Likely Benign	0.24	Likely Benign	0.324	Likely Benign	-3.34	Deleterious	0.997	Probably Damaging	0.966	Probably Damaging	3.47	Benign	0.16	Tolerated			0.2943	0.0789		0	1	0.4	0.94
c.1326A>C	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1326A>T	K442N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K442N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and the folding‑stability method Foldetta (which integrates FoldX‑MD and Rosetta outputs). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward pathogenicity, but the presence of several strong benign predictions and a benign folding‑stability result introduces uncertainty. Based on the current computational evidence, the variant is most likely pathogenic, and this does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.255766	Uncertain	0.912	0.225	0.000											-11.039	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.37	Likely Benign	0.1	0.53	Ambiguous	0.45	Likely Benign	0.31	Likely Benign	0.161	Likely Benign	-4.05	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.46	Benign	0.10	Tolerated			0.2686	0.1314		1	0	0.4	-14.07
c.1330A>C	K444Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K444Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (majority vote) is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K444Q, and this conclusion does not conflict with any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-12.876	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	1.34	Ambiguous	0.0	1.36	Ambiguous	1.35	Ambiguous	1.04	Destabilizing	0.382	Likely Benign	-3.82	Deleterious	0.998	Probably Damaging	0.997	Probably Damaging	3.43	Benign	0.07	Tolerated			0.4112	0.1057		1	1	0.4	-0.04
c.1330A>G	K444E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K444E 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 predictors—including FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic effect. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-15.571	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.99	Destabilizing	0.1	3.75	Destabilizing	3.37	Destabilizing	1.10	Destabilizing	0.437	Likely Benign	-3.82	Deleterious	0.997	Probably Damaging	0.981	Probably Damaging	3.40	Benign	0.01	Affected			0.3486	0.0793		0	1	0.4	0.94
c.1332G>C	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the majority of tools (FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta’s stability assessment is uncertain and therefore not used as evidence. Overall, the preponderance of evidence points to a pathogenic effect for K444N. This conclusion is not contradicted by ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1332G>T	K444N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K444N 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. Tools that predict a pathogenic effect include FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact. There is no ClinVar annotation to contradict this assessment, so the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.262172	Uncertain	0.955	0.213	0.000											-14.797	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	2.41	Destabilizing	0.0	1.52	Ambiguous	1.97	Ambiguous	1.18	Destabilizing	0.286	Likely Benign	-4.77	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	3.39	Benign	0.01	Affected			0.3282	0.1213		1	0	0.4	-14.07
c.1345A>G	S449G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449G is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (variant ID 6‑33438250‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as “Likely Benign,” and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000					Uncertain		1	6-33438250-A-G	3	1.86e-6	-5.936	Likely Benign	0.071	Likely Benign	Likely Benign	0.47	Likely Benign	0.0	0.55	Ambiguous	0.51	Ambiguous	0.85	Ambiguous	0.116	Likely Benign	-2.32	Neutral	0.948	Possibly Damaging	0.124	Benign	3.35	Benign	0.13	Tolerated	3.37	32	0.2600	0.3718		0	1	0.4	-30.03
c.1351C>G	L451V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L451V 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. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain and does not contribute to the consensus. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic; and Foldetta predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for L451V. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000											-10.732	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	2.83	Destabilizing	0.1	1.81	Ambiguous	2.32	Destabilizing	1.39	Destabilizing	0.325	Likely Benign	-2.90	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	2.54	Benign	0.01	Affected			0.1065	0.2856		2	1	0.4	-14.03
c.1363C>G	L455V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L455V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions come from REVEL and FATHMM, whereas the remaining 11 tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict pathogenicity. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.188120	Structured	0.310377	Uncertain	0.963	0.168	0.000											-12.773	Likely Pathogenic	0.946	Likely Pathogenic	Ambiguous	2.89	Destabilizing	0.1	2.38	Destabilizing	2.64	Destabilizing	1.41	Destabilizing	0.276	Likely Benign	-2.83	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.29	Benign	0.02	Affected			0.1149	0.3056		2	1	0.4	-14.03
c.1369A>G	S457G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S457G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for S457G. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.164327	Structured	0.297330	Uncertain	0.909	0.159	0.000											-9.154	Likely Pathogenic	0.811	Likely Pathogenic	Ambiguous	0.86	Ambiguous	0.0	0.87	Ambiguous	0.87	Ambiguous	0.65	Ambiguous	0.382	Likely Benign	-3.82	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	3.35	Benign	0.13	Tolerated			0.2735	0.4074		1	0	0.4	-30.03
c.1378A>C	K460Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K460Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, SIFT, and FATHMM, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive include FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments give a pathogenic consensus from the SGM method (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and an uncertain result from AlphaMissense‑Optimized; Foldetta likewise reports no definitive stability change. 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	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-9.404	Likely Pathogenic	0.793	Likely Pathogenic	Ambiguous	0.71	Ambiguous	0.0	0.86	Ambiguous	0.79	Ambiguous	0.86	Ambiguous	0.312	Likely Benign	-3.15	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.14	Tolerated			0.4523	0.1454		1	1	0.4	-0.04
c.1378A>G	K460E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K460E is not 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, a majority of tools predict a pathogenic impact: AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), Rosetta, and premPS all indicate pathogenicity, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No prediction or folding‑stability result is missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for K460E, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.155435	Structured	0.289547	Uncertain	0.938	0.150	0.125											-13.304	Likely Pathogenic	0.982	Likely Pathogenic	Likely Pathogenic	1.68	Ambiguous	0.0	2.02	Destabilizing	1.85	Ambiguous	1.05	Destabilizing	0.398	Likely Benign	-3.40	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	3.34	Benign	0.09	Tolerated			0.3966	0.1022		0	1	0.4	0.94
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.1384A>C	K462Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K462Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, SIFT, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. Overall, the majority of tools and the protein‑stability analysis favor a benign effect, while the consensus pathogenic score introduces uncertainty. Thus, the variant is most likely benign; this assessment does not contradict ClinVar status, which has no entry for K462Q. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.144	Likely Pathogenic	0.809	Likely Pathogenic	Ambiguous	0.12	Likely Benign	0.1	0.34	Likely Benign	0.23	Likely Benign	0.48	Likely Benign	0.384	Likely Benign	-3.85	Deleterious	0.999	Probably Damaging	0.999	Probably Damaging	3.40	Benign	0.15	Tolerated			0.4639	0.1286		1	1	0.4	-0.04
c.1384A>G	K462E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, and FATHMM. Tools that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta and Foldetta are uncertain and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta is uncertain. Overall, the majority of predictions (7 pathogenic vs. 5 benign) and the high‑accuracy tools support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-14.696	Likely Pathogenic	0.967	Likely Pathogenic	Likely Pathogenic	0.34	Likely Benign	0.0	1.56	Ambiguous	0.95	Ambiguous	0.33	Likely Benign	0.433	Likely Benign	-3.88	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.49	Benign	0.15	Tolerated			0.4145	0.1022		0	1	0.4	0.94
c.1386G>C	K462N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K462N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, and the SGM Consensus also indicates Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result, providing no definitive evidence. Overall, the majority of high‑confidence predictors lean toward pathogenicity, contradicting the absence of a ClinVar classification. Thus, the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125											-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.304	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1386G>T	K462N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K462N is reported in gnomAD (ID 6‑33438291‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, premPS) and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM Consensus as likely pathogenic, while Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K462N. This conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125								6-33438291-G-T	1	6.20e-7	-12.823	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.69	Ambiguous	0.1	1.67	Ambiguous	1.18	Ambiguous	0.90	Ambiguous	0.303	Likely Benign	-4.83	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.42	Benign	0.07	Tolerated	3.37	34	0.3967	0.1242		0	1	0.4	-14.07
c.1393C>G	L465V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while the remaining tools—FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default—indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports likely pathogenic; and Foldetta, which combines FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar uncertain status and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000					Uncertain		1				-9.893	Likely Pathogenic	0.838	Likely Pathogenic	Ambiguous	2.46	Destabilizing	0.1	2.66	Destabilizing	2.56	Destabilizing	1.21	Destabilizing	0.276	Likely Benign	-2.98	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.44	Pathogenic	0.10	Tolerated	3.37	34	0.1493	0.3378		2	1	0.4	-14.03	204.3	30.9	0.0	0.0	-0.4	0.6						X		Potentially Benign	The iso-butyl side chain of Leu465, located in the middle of an α helix (res. Ala461–Phe476), packs with hydrophobic residues (e.g., Phe464, Met468, Tyr497, Ile494) in an inter-helix space formed with two other α helices (res. Ala461–Phe476 and res. Thr488-Gly502). In the variant simulations, the iso-propyl side chain of Val465 is equally sized and similarly hydrophobic as the original side chain of Leu465. Hence, the mutation does not exert any negative effects on the protein structure based on the variant simulations.
c.1444C>G	L482V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT and AlphaMissense‑Optimized, whereas a majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—indicates pathogenicity; Foldetta remains uncertain. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.676	Likely Pathogenic	0.734	Likely Pathogenic	Likely Benign	1.97	Ambiguous	0.1	1.52	Ambiguous	1.75	Ambiguous	0.76	Ambiguous	0.709	Likely Pathogenic	-2.95	Deleterious	0.989	Probably Damaging	0.984	Probably Damaging	-1.30	Pathogenic	0.10	Tolerated			0.1074	0.2027		2	1	0.4	-14.03
c.1465C>G	L489V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, while only AlphaMissense‑Optimized predicts a benign outcome. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for L489V. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database record. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125											-9.345	Likely Pathogenic	0.467	Ambiguous	Likely Benign	2.09	Destabilizing	0.0	1.70	Ambiguous	1.90	Ambiguous	1.25	Destabilizing	0.586	Likely Pathogenic	-2.55	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.34	Pathogenic	0.01	Affected			0.1665	0.4108		2	1	0.4	-14.03
c.1474A>C	K492Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K492Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, and FATHMM, whereas pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, SGM Consensus confirms a likely pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from ClinVar contradicts these findings. Therefore, the variant is most likely pathogenic based on the collective predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-14.685	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.34	Likely Benign	0.0	0.93	Ambiguous	0.64	Ambiguous	1.13	Destabilizing	0.463	Likely Benign	-3.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.98	Benign	0.02	Affected			0.3534	0.0830		1	1	0.4	-0.04
c.1474A>G	K492E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K492E is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that classify the variant as benign include only FATHMM. The remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores it as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, which contradicts its current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000					Conflicting		2				-16.175	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.53	Ambiguous	0.1	1.90	Ambiguous	1.72	Ambiguous	1.42	Destabilizing	0.510	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.99	Benign	0.01	Affected	3.37	35	0.2968	0.0650		1	0	0.4	0.94
c.1476A>C	K492N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K492N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly 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, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No folding‑stability predictions are definitive. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-14.048	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.09	Ambiguous	1.01	Ambiguous	1.25	Destabilizing	0.512	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.92	Benign	0.00	Affected			0.2814	0.0926		1	0	0.4	-14.07
c.1476A>T	K492N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K492N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly 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, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No folding‑stability predictions are definitive. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.327121	Uncertain	0.947	0.192	0.000											-14.048	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.09	Ambiguous	1.01	Ambiguous	1.25	Destabilizing	0.512	Likely Pathogenic	-4.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.92	Benign	0.00	Affected			0.2814	0.0926		1	0	0.4	-14.07
c.1498C>G	L500V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L500V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on benign effect include SIFT and AlphaMissense‑Optimized, whereas a majority of tools predict pathogenicity: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Predictions that are inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000											-12.963	Likely Pathogenic	0.379	Ambiguous	Likely Benign	1.92	Ambiguous	0.0	0.81	Ambiguous	1.37	Ambiguous	1.11	Destabilizing	0.565	Likely Pathogenic	-2.98	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated			0.1205	0.1860		2	1	0.4	-14.03
c.1510A>C	K504Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K504Q 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, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta predicts a benign stability change. Overall, seven tools support a benign outcome while four support pathogenicity, with no ClinVar evidence to contradict this assessment. 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.		GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-6.685	Likely Benign	0.238	Likely Benign	Likely Benign	0.13	Likely Benign	0.2	-0.01	Likely Benign	0.06	Likely Benign	0.91	Ambiguous	0.269	Likely Benign	-3.07	Deleterious	0.945	Possibly Damaging	0.918	Probably Damaging	-1.37	Pathogenic	0.46	Tolerated			0.3104	0.0780		1	1	0.4	-0.04
c.1510A>G	K504E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K504E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-9.890	Likely Pathogenic	0.587	Likely Pathogenic	Likely Benign	0.63	Ambiguous	0.4	0.78	Ambiguous	0.71	Ambiguous	1.06	Destabilizing	0.386	Likely Benign	-3.40	Deleterious	0.924	Possibly Damaging	0.674	Possibly Damaging	-1.25	Pathogenic	0.21	Tolerated			0.2583	0.0650		0	1	0.4	0.94
c.1512A>C	K504N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K504N is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (8/13) predict pathogenicity, while 4 predict benign and one is uncertain. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, which is currently absent. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-8.908	Likely Pathogenic	0.720	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	0.57	Ambiguous	0.42	Likely Benign	1.00	Destabilizing	0.430	Likely Benign	-4.37	Deleterious	0.993	Probably Damaging	0.922	Probably Damaging	-1.44	Pathogenic	0.07	Tolerated			0.2470	0.0926		1	0	0.4	-14.07
c.1512A>T	K504N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K504N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, AlphaMissense‑Optimized, and the folding‑stability method Foldetta. Tools that predict a pathogenic effect comprise SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it likely pathogenic, and Foldetta indicating a benign folding‑stability outcome. Overall, the majority of predictions (8 out of 13) support a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.304984	Uncertain	0.850	0.189	0.000											-8.908	Likely Pathogenic	0.720	Likely Pathogenic	Likely Benign	0.26	Likely Benign	0.2	0.57	Ambiguous	0.42	Likely Benign	1.00	Destabilizing	0.430	Likely Benign	-4.37	Deleterious	0.993	Probably Damaging	0.922	Probably Damaging	-1.44	Pathogenic	0.07	Tolerated			0.2470	0.0926		1	0	0.4	-14.07
c.1516C>G	L506V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM Consensus) all indicate a pathogenic impact. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-10.220	Likely Pathogenic	0.512	Ambiguous	Likely Benign	2.61	Destabilizing	0.2	3.27	Destabilizing	2.94	Destabilizing	1.36	Destabilizing	0.420	Likely Benign	-2.98	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	1.62	Pathogenic	0.04	Affected			0.1126	0.1660		2	1	0.4	-14.03
c.1519A>C	K507Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Uncertain results come from Rosetta, premPS, and ESM1b. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is benign. Taken together, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-7.698	In-Between	0.180	Likely Benign	Likely Benign	0.28	Likely Benign	0.0	-0.70	Ambiguous	-0.21	Likely Benign	-0.52	Ambiguous	0.443	Likely Benign	0.22	Neutral	0.999	Probably Damaging	0.999	Probably Damaging	-1.52	Pathogenic	0.86	Tolerated			0.2952	0.0713		1	1	0.4	-0.04
c.1519A>G	K507E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K507E missense change is not listed in ClinVar and has no gnomAD allele, indicating it is not a common polymorphism. Functional prediction tools cluster into two groups: benign predictions come from Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Four tools give uncertain results: FoldX, Foldetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments provide a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) leans pathogenic, and Foldetta remains uncertain. Overall, the majority of standard predictors favor a pathogenic effect, and the high‑accuracy consensus also tilts toward pathogenicity, though not decisively. Therefore, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-11.507	Likely Pathogenic	0.448	Ambiguous	Likely Benign	0.70	Ambiguous	0.0	0.31	Likely Benign	0.51	Ambiguous	0.67	Ambiguous	0.536	Likely Pathogenic	-0.84	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	-1.45	Pathogenic	0.21	Tolerated			0.2537	0.0488		0	1	0.4	0.94
c.1521G>C	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas a pathogenic signal is reported by REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta give uncertain results. 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’s stability prediction is unavailable. Overall, the majority of tools (10 out of 14 with definitive calls) predict a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists. Thus, the variant is most likely pathogenic based on the available computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1521G>T	K507N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K507N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta, PROVEAN, SIFT, and AlphaMissense‑Optimized, while those that predict a pathogenic effect comprise REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (10 pathogenic vs. 4 benign) predict a deleterious impact. Thus, 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	0.019401	Structured	0.262601	Uncertain	0.885	0.222	0.000											-10.682	Likely Pathogenic	0.739	Likely Pathogenic	Likely Benign	0.81	Ambiguous	0.1	0.18	Likely Benign	0.50	Ambiguous	1.06	Destabilizing	0.579	Likely Pathogenic	-1.63	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	-1.57	Pathogenic	0.11	Tolerated			0.2417	0.0764		1	0	0.4	-14.07
c.1549C>G	L517V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L517V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree that the change is deleterious: pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM, while benign predictions are made by SIFT and AlphaMissense‑Optimized; the remaining tools (Rosetta, Foldetta, AlphaMissense‑Default) are uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Overall, the preponderance of evidence points to a likely pathogenic effect of the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.147645	Uncertain	0.938	0.296	0.000											-10.691	Likely Pathogenic	0.498	Ambiguous	Likely Benign	2.04	Destabilizing	0.3	1.37	Ambiguous	1.71	Ambiguous	1.14	Destabilizing	0.577	Likely Pathogenic	-2.68	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.26	Pathogenic	0.17	Tolerated			0.1405	0.2398		2	1	0.4	-14.03
c.1588A>C	K530Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (13/16) predict pathogenicity, whereas only three predict benign. 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	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-10.593	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	0.31	Likely Benign	0.0	0.87	Ambiguous	0.59	Ambiguous	0.13	Likely Benign	0.524	Likely Pathogenic	-3.18	Deleterious	0.698	Possibly Damaging	0.694	Possibly Damaging	-1.61	Pathogenic	0.01	Affected			0.3001	0.0941		1	1	0.4	-0.04
c.1588A>G	K530E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K530E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and polyPhen‑2 HumVar, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus remains Likely Pathogenic, and Foldetta is uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K530E. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-14.450	Likely Pathogenic	0.951	Likely Pathogenic	Ambiguous	0.79	Ambiguous	0.2	1.27	Ambiguous	1.03	Ambiguous	0.43	Likely Benign	0.581	Likely Pathogenic	-3.45	Deleterious	0.703	Possibly Damaging	0.276	Benign	-1.57	Pathogenic	0.00	Affected			0.2505	0.0810		0	1	0.4	0.94
c.1590G>C	K530N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10/13) support pathogenicity, with only three tools indicating benign. Therefore, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.459	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.23	Likely Benign	0.33	Likely Benign	0.56	Ambiguous	0.553	Likely Pathogenic	-4.18	Deleterious	0.950	Possibly Damaging	0.703	Possibly Damaging	-1.65	Pathogenic	0.00	Affected			0.2350	0.1086		1	0	0.4	-14.07
c.1590G>T	K530N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, and Foldetta, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—predict a pathogenic or likely pathogenic outcome; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as benign. Overall, the majority of predictions (10/13) support pathogenicity, with only three tools indicating benign. Therefore, the variant is most likely pathogenic based on the available computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000											-12.459	Likely Pathogenic	0.960	Likely Pathogenic	Likely Pathogenic	0.42	Likely Benign	0.1	0.23	Likely Benign	0.33	Likely Benign	0.56	Ambiguous	0.553	Likely Pathogenic	-4.18	Deleterious	0.950	Possibly Damaging	0.703	Possibly Damaging	-1.65	Pathogenic	0.00	Affected			0.2350	0.1086		1	0	0.4	-14.07
c.1603A>G	S535G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S535G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. Uncertain or inconclusive results come from Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for S535G, and this conclusion does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.236433	Structured	0.041365	Uncertain	0.918	0.343	0.000											-4.619	Likely Benign	0.143	Likely Benign	Likely Benign	0.19	Likely Benign	0.0	0.93	Ambiguous	0.56	Ambiguous	0.64	Ambiguous	0.247	Likely Benign	-1.75	Neutral	0.606	Possibly Damaging	0.114	Benign	-1.30	Pathogenic	0.19	Tolerated			0.2858	0.4644		1	0	0.4	-30.03
c.1606T>G	L536V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L536V is listed in ClinVar (ID 1690714.0) with an uncertain significance designation and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic verdict. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. No evidence from FoldX or Rosetta alone is available. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.137348	Structured	0.042188	Uncertain	0.931	0.341	0.000					Uncertain		1				-9.014	Likely Pathogenic	0.269	Likely Benign	Likely Benign	1.25	Ambiguous	0.3	1.22	Ambiguous	1.24	Ambiguous	1.20	Destabilizing	0.586	Likely Pathogenic	-2.81	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.34	Pathogenic	0.09	Tolerated	3.37	34	0.1591	0.3565		2	1	0.4	-14.03	204.7	26.4	0.2	0.0	-0.2	0.2						X		Potentially Benign	Leu536 is located on an α-helix (res. Ala533-Val560) at the membrane interface. The iso-butyl group of Leu536 interacts with nearby hydrophobic residues in the preceding loop (e.g., Val526, Pro528, Cys531). In the variant simulations, the iso-propyl side chain of Val536 forms similar hydrophobic interactions as Leu536 in the WT, causing no negative structural effects.
c.1627C>G	L543V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. AlphaMissense‑Optimized is inconclusive (uncertain). High‑accuracy assessments further support pathogenicity: the SGM‑Consensus predicts “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains uncertain. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000											-11.561	Likely Pathogenic	0.908	Likely Pathogenic	Ambiguous	3.09	Destabilizing	0.3	2.03	Destabilizing	2.56	Destabilizing	1.28	Destabilizing	0.398	Likely Benign	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.99	Pathogenic	0.01	Affected			0.1334	0.2028		2	1	0.4	-14.03
c.1645T>G	L549V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L549V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include Rosetta, PROVEAN, and SIFT, whereas a majority of tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default) predict a pathogenic impact. Four tools (FoldX, Foldetta, premPS, and AlphaMissense‑Optimized) give uncertain or inconclusive results. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic interpretation. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.007921	Uncertain	0.955	0.281	0.000											-9.379	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	1.22	Ambiguous	0.3	0.27	Likely Benign	0.75	Ambiguous	0.88	Ambiguous	0.544	Likely Pathogenic	-2.32	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	-1.23	Pathogenic	0.21	Tolerated			0.1400	0.1860		2	1	0.4	-14.03
c.1651C>G	L551V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools give uncertain results: AlphaMissense‑Default and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic impact for L551V. This conclusion does not contradict ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000											-10.154	Likely Pathogenic	0.556	Ambiguous	Likely Benign	2.04	Destabilizing	0.0	1.41	Ambiguous	1.73	Ambiguous	1.03	Destabilizing	0.575	Likely Pathogenic	-1.39	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	-1.48	Pathogenic	0.22	Tolerated			0.1376	0.2778		2	1	0.4	-14.03
c.1657A>C	K553Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K553Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Foldetta, and SIFT, whereas the majority of tools (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict it to be pathogenic; Rosetta is inconclusive and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, all pathogenic) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence (10 pathogenic vs. 3 benign predictions) indicates that K553Q is most likely pathogenic, 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	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000											-13.476	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.44	Likely Benign	0.1	0.53	Ambiguous	0.49	Likely Benign	1.01	Destabilizing	0.783	Likely Pathogenic	-3.78	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.37	Pathogenic	0.07	Tolerated			0.3477	0.0830		1	1	0.4	-0.04
c.1657A>G	K553E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K553E missense variant is not reported in ClinVar (status: None) and has no entries in gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the remaining tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict pathogenicity. FoldX and Rosetta give uncertain results, and Foldetta also reports an uncertain stability change. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a deleterious effect. Thus, the variant is most likely pathogenic based on current predictions, 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	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000											-17.415	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.3	1.15	Ambiguous	1.12	Ambiguous	1.04	Destabilizing	0.828	Likely Pathogenic	-3.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.35	Pathogenic	0.12	Tolerated			0.2890	0.0650		0	1	0.4	0.94
c.1659G>C	K553N 2D 3DClick to see structure in 3D Viewer AISynGAP1 K553N is not reported in ClinVar and is present in gnomAD (6-33438902-G-C). Functional prediction tools largely agree on a deleterious effect: SIFT is the sole benign predictor, whereas REVEL, SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. FoldX, Rosetta, and Foldetta return uncertain results. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Overall, the consensus of the majority of tools indicates that K553N is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000								6-33438902-G-C	1	6.20e-7	-13.664	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.62	Ambiguous	0.63	Ambiguous	1.11	Destabilizing	0.566	Likely Pathogenic	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated	3.37	35	0.2758	0.0926		0	1	0.4	-14.07
c.1659G>T	K553N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K553N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of algorithms (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Taken together, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.012270	Structured	0.006539	Uncertain	0.949	0.246	0.000											-13.664	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.63	Ambiguous	0.0	0.62	Ambiguous	0.63	Ambiguous	1.11	Destabilizing	0.566	Likely Pathogenic	-4.77	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated	3.37	35	0.2758	0.0926		0	1	0.4	-14.07
c.166C>G	L56V 2D AIThe SynGAP1 missense variant L56V is not 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, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs 1 pathogenic, 1 uncertain). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the L56V variant, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.342579	Structured	0.476218	Uncertain	0.495	0.657	0.000											-8.104	Likely Pathogenic	0.471	Ambiguous	Likely Benign										0.123	Likely Benign	-0.99	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	3.90	Benign	0.00	Affected			0.1635	0.3655		2	1	0.4	-14.03
c.1693C>G	L565V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565V has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two consensus groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Two tools (AlphaMissense‑Optimized and Rosetta) give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a pathogenic impact on protein stability. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000											-11.118	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	2.69	Destabilizing	0.0	1.37	Ambiguous	2.03	Destabilizing	1.40	Destabilizing	0.303	Likely Benign	-2.99	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.87	Benign	0.03	Affected			0.1558	0.2488		2	1	0.4	-14.03
c.1696A>C	K566Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566Q has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include SIFT and Rosetta, whereas a majority of tools predict a pathogenic impact: REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, premPS, PROVEAN, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta as uncertain. Because the preponderance of evidence points to a deleterious effect, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-11.475	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	1.48	Ambiguous	0.1	-0.35	Likely Benign	0.57	Ambiguous	1.25	Destabilizing	0.762	Likely Pathogenic	-3.52	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.42	Pathogenic	0.07	Tolerated			0.3824	0.1282		1	1	0.4	-0.04
c.1696A>G	K566E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K566E missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Across the evaluated tools, every predictor that returned a definitive call classified the variant as pathogenic: SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reported a benign outcome; the only inconclusive result was from Rosetta, which was labeled “Uncertain.” High‑accuracy assessments—AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta—each returned a pathogenic prediction. Consequently, the variant is most likely pathogenic based on the consensus of predictive algorithms, and this assessment does not contradict any existing ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-10.759	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.76	Destabilizing	0.2	1.13	Ambiguous	2.45	Destabilizing	1.58	Destabilizing	0.832	Likely Pathogenic	-3.58	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.38	Pathogenic	0.04	Affected			0.3275	0.0850		0	1	0.4	0.94
c.1698G>C	K566N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while Rosetta is uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000											-11.255	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.83	Destabilizing	0.3	1.33	Ambiguous	2.08	Destabilizing	1.32	Destabilizing	0.683	Likely Pathogenic	-4.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.03	Affected	3.37	35	0.3042	0.1567		0	1	0.4	-14.07
c.1698G>T	K566N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K566N is listed in gnomAD (variant ID 6‑33440750‑G‑T) but has no ClinVar entry. All available in‑silico predictors that provide a definitive call classify the substitution as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tool with an inconclusive result is Rosetta (Uncertain), which is treated as unavailable evidence. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Consequently, the variant is most likely pathogenic based on current predictions, and this conclusion does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.027463	Structured	0.047887	Uncertain	0.924	0.219	0.000								6-33440750-G-T			-11.255	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.83	Destabilizing	0.3	1.33	Ambiguous	2.08	Destabilizing	1.32	Destabilizing	0.683	Likely Pathogenic	-4.04	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.43	Pathogenic	0.03	Affected	3.37	35	0.3042	0.1567		0	1	0.4	-14.07
c.169C>G	L57V 2D AIThe SynGAP1 missense variant L57V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for the variant, 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		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-3.598	Likely Benign	0.256	Likely Benign	Likely Benign										0.051	Likely Benign	-0.14	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	4.17	Benign	0.00	Affected			0.1533	0.4006		2	1	0.4	-14.03
c.1720C>G	L574V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L574V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM 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 show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. No other high‑confidence pathogenic predictions are present. Based on the preponderance of benign predictions and the lack of any ClinVar pathogenic annotation, the variant is most likely benign. 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 Benign	GAP	0.083462	Structured	0.026427	Uncertain	0.927	0.246	0.000											-5.559	Likely Benign	0.105	Likely Benign	Likely Benign	0.78	Ambiguous	0.1	0.37	Likely Benign	0.58	Ambiguous	0.25	Likely Benign	0.149	Likely Benign	-0.40	Neutral	0.004	Benign	0.003	Benign	-1.27	Pathogenic	0.29	Tolerated			0.1481	0.2978		2	1	0.4	-14.03
c.175C>G	L59V 2D AIThe SynGAP1 missense variant L59V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the absence of a ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000											-4.465	Likely Benign	0.588	Likely Pathogenic	Likely Benign										0.049	Likely Benign	-1.15	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	3.36	Benign	0.00	Affected			0.1508	0.3217		2	1	0.4	-14.03
c.1762C>G	L588V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SIFT classifies it as benign, whereas the remaining 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect for L588V. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. 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	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-10.374	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	3.61	Destabilizing	0.4	2.81	Destabilizing	3.21	Destabilizing	1.24	Destabilizing	0.533	Likely Pathogenic	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.28	Pathogenic	0.08	Tolerated			0.1422	0.2228		2	1	0.4	-14.03
c.1768A>G	S590G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S590G is listed in ClinVar (ID 1721675.0) with an uncertain significance status and is present in gnomAD (6‑33440820‑A‑G). Functional prediction tools that report a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic majority. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive, as are FoldX, Rosetta, and premPS. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022667	Structured	0.088943	Uncertain	0.918	0.199	0.000					Conflicting		2	6-33440820-A-G	14	8.67e-6	-14.277	Likely Pathogenic	0.574	Likely Pathogenic	Likely Benign	0.67	Ambiguous	0.1	1.28	Ambiguous	0.98	Ambiguous	0.71	Ambiguous	0.379	Likely Benign	-3.92	Deleterious	1.000	Probably Damaging	0.922	Probably Damaging	3.42	Benign	0.06	Tolerated	3.37	35	0.2627	0.4118		1	0	0.4	-30.03	186.7	49.4	0.0	0.0	0.1	0.0		X						Potentially Pathogenic	In the WT simulations, the hydroxyl group of Ser590, located on an α helix (res. Glu582-Met603), forms hydrogen bonds with the backbone carbonyl of Ala634 and/or the carboxamide group of the Asn635 side chain at the end of the opposing α helix (res. Thr619-Ala634).The residue swap could weaken the integrity of the α helix, as glycine is known as an “α helix breaker.” However, no discernible difference was observed between the WT and variant simulations in this regard. Importantly, Gly590 cannot form hydrogen bonds with the opposing helix in the same way that serine can, which could weaken the tertiary structure assembly between the two helices.
c.1777C>G	L593V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L593V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Uncertain or inconclusive results come from Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic prediction; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain. Overall, the majority of evidence (six pathogenic vs. four benign) points to a pathogenic effect. 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	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-10.327	Likely Pathogenic	0.551	Ambiguous	Likely Benign	2.81	Destabilizing	0.2	1.10	Ambiguous	1.96	Ambiguous	1.39	Destabilizing	0.268	Likely Benign	-2.59	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.04	Benign	0.12	Tolerated			0.1599	0.3577		2	1	0.4	-14.03
c.1783C>G	L595V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L595V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, and FATHMM, while pathogenic calls are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked uncertain include FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy consensus methods give a clearer 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) is also inconclusive. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000											-13.490	Likely Pathogenic	0.905	Likely Pathogenic	Ambiguous	1.29	Ambiguous	0.1	0.24	Likely Benign	0.77	Ambiguous	1.01	Destabilizing	0.398	Likely Benign	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	2.78	Benign	0.01	Affected			0.1441	0.3406		2	1	0.4	-14.03
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.1816A>G	S606G 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant S606G is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result and is treated as unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000											-12.281	Likely Pathogenic	0.603	Likely Pathogenic	Likely Benign	0.43	Likely Benign	0.1	1.42	Ambiguous	0.93	Ambiguous	0.84	Ambiguous	0.229	Likely Benign	-3.98	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	3.35	Benign	0.04	Affected			0.2286	0.3279		1	0	0.4	-30.03
c.1819C>G	L607V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607V is listed in ClinVar with an uncertain significance (ClinVar ID 1450275.0) and is present in gnomAD (ID 6‑33440871‑C‑G). Prediction tools that agree on a benign effect include only AlphaMissense‑Optimized. All other evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized reports benign, whereas the SGM‑Consensus, derived from the majority of pathogenic predictions, indicates pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive and therefore not considered evidence. Overall, the preponderance of computational evidence points to a pathogenic effect for L607V, a conclusion that contrasts with the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000					Uncertain		2	6-33440871-C-G	2	1.24e-6	-11.190	Likely Pathogenic	0.637	Likely Pathogenic	Likely Benign	1.04	Ambiguous	0.2	1.36	Ambiguous	1.20	Ambiguous	0.90	Ambiguous	0.715	Likely Pathogenic	-2.99	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.50	Pathogenic	0.01	Affected	3.37	35	0.1634	0.3577		2	1	0.4	-14.03	216.3	28.1	0.1	0.0	0.9	0.2				X				Potentially Benign	Leu607 is located in a short helical region (res. Ser606-Phe608) within an α-α loop connecting two α helices (res. Glu582-Met603 and res. Glu617-Asn635). In the WT simulations, the iso-butyl side chain of Leu607 does not interact with any other residues, but it could potentially interact directly with Ras due to its location at the GAP domain.In the variant simulations, Val607, which has similar size and physicochemical properties to leucine, does not cause any negative effects on the protein structure. However, due to its location at the GAP-Ras interface, the residue swap could affect the complex formation with the GTPase, but this cannot be investigated using solvent-only simulations.
c.1828C>G	L610V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L610V is reported in gnomAD (ID 6‑33440880‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM, while only AlphaMissense‑Optimized predicts a benign outcome. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates benign, whereas the SGM Consensus remains pathogenic and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. With the overwhelming majority of tools predicting pathogenicity and no ClinVar evidence to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-G	3	1.86e-6	-11.304	Likely Pathogenic	0.474	Ambiguous	Likely Benign	2.24	Destabilizing	0.3	0.76	Ambiguous	1.50	Ambiguous	1.21	Destabilizing	0.740	Likely Pathogenic	-2.86	Deleterious	0.985	Probably Damaging	0.992	Probably Damaging	-1.46	Pathogenic	0.01	Affected	3.37	35	0.1515	0.3039		1	2	0.4	-14.03
c.1867C>G	L623V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623V is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Rosetta and AlphaMissense‑Optimized give uncertain results. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic, and AlphaMissense‑Optimized remains 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 classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-12.802	Likely Pathogenic	0.896	Likely Pathogenic	Ambiguous	3.96	Destabilizing	0.3	1.84	Ambiguous	2.90	Destabilizing	1.45	Destabilizing	0.416	Likely Benign	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.60	Pathogenic	0.01	Affected			0.1653	0.3588		2	1	0.4	-14.03
c.1873C>G	L625V 2D AISynGAP1 missense variant L625V is listed in ClinVar with an uncertain significance (ClinVar ID 3392716.0) 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, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000					Uncertain		1				-11.319	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	1.80	Ambiguous	0.7	1.69	Ambiguous	1.75	Ambiguous	1.42	Destabilizing	0.480	Likely Benign	-2.96	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.07	Benign	0.01	Affected			0.1306	0.3427		2	1	0.4	-14.03
c.1882A>C	K628Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K628Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, and Foldetta, all of which score the variant as benign. In contrast, the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The premPS tool yields an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000											-12.263	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.46	Likely Benign	0.0	-0.16	Likely Benign	0.15	Likely Benign	0.95	Ambiguous	0.587	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.46	Pathogenic	0.00	Affected			0.3444	0.1358		1	1	0.4	-0.04
c.1882A>G	K628E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K628E 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 pathogenic effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that are inconclusive or uncertain are FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Overall, the majority of evidence points to a deleterious effect. The variant is most likely pathogenic based on these predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000											-14.658	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	1.04	Ambiguous	0.2	0.52	Ambiguous	0.78	Ambiguous	1.06	Destabilizing	0.652	Likely Pathogenic	-3.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.37	Pathogenic	0.00	Affected			0.2909	0.0810		0	1	0.4	0.94
c.1884G>C	K628N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K628N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic or likely pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability predictions and are therefore treated as unavailable evidence. High‑accuracy assessments specifically show AlphaMissense‑Optimized predicting pathogenicity, the SGM‑Consensus indicating a likely pathogenic status, and Foldetta yielding an uncertain result. Based on the overwhelming agreement among the majority of prediction tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000											-12.284	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.1	0.59	Ambiguous	0.69	Ambiguous	1.11	Destabilizing	0.403	Likely Benign	-4.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.37	Pathogenic	0.00	Affected	3.37	34	0.2740	0.1254		0	1	0.4	-14.07
c.1884G>T	K628N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K628N is catalogued in gnomAD (6‑33440936‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: a single benign prediction from REVEL, and a consensus of nine pathogenic predictions from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also labels the variant as Likely Pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus confirms a likely pathogenic status, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result and therefore does not alter the overall interpretation. Consequently, the variant is most likely pathogenic according to the available computational evidence, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.088832	Structured	0.035486	Uncertain	0.957	0.229	0.000								6-33440936-G-T	1	6.20e-7	-12.284	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.78	Ambiguous	0.1	0.59	Ambiguous	0.69	Ambiguous	1.11	Destabilizing	0.403	Likely Benign	-4.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.37	Pathogenic	0.00	Affected	3.37	34	0.2740	0.1254		0	1	0.4	-14.07
c.1897C>G	L633V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633V is not reported in ClinVar and is present in the gnomAD database (ID 6‑33440949‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, SGM‑Consensus, and Foldetta; the Rosetta score is uncertain and therefore not considered. High‑accuracy methods give a pathogenic consensus: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta both predict pathogenic. Overall, the majority of evidence supports a pathogenic impact for L633V, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000								6-33440949-C-G	1	6.20e-7	-9.992	Likely Pathogenic	0.760	Likely Pathogenic	Likely Benign	2.32	Destabilizing	0.2	1.71	Ambiguous	2.02	Destabilizing	1.32	Destabilizing	0.327	Likely Benign	-2.99	Deleterious	0.996	Probably Damaging	0.992	Probably Damaging	2.86	Benign	0.03	Affected	3.37	34	0.1517	0.2766		1	2	0.4	-14.03
c.1912A>C	K638Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K638Q 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. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default remains uncertain. 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 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	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.561	Likely Pathogenic	0.556	Ambiguous	Likely Benign	0.45	Likely Benign	0.0	0.37	Likely Benign	0.41	Likely Benign	0.22	Likely Benign	0.421	Likely Benign	-3.60	Deleterious	0.997	Probably Damaging	0.991	Probably Damaging	3.42	Benign	0.12	Tolerated			0.3623	0.0920		1	1	0.4	-0.04
c.1912A>G	K638E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638E is not 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, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Predictions from FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are uncertain or 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 uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict 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	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-13.390	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.0	1.00	Ambiguous	0.79	Ambiguous	0.32	Likely Benign	0.363	Likely Benign	-3.70	Deleterious	0.995	Probably Damaging	0.947	Probably Damaging	3.50	Benign	0.12	Tolerated			0.3036	0.0790		0	1	0.4	0.94
c.1914G>C	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1914G>T	K638N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K638N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), and Foldetta as uncertain. Overall, the balance of evidence favors a pathogenic classification; this conclusion does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.098064	Uncertain	0.937	0.260	0.000											-9.420	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.74	Ambiguous	0.1	0.90	Ambiguous	0.82	Ambiguous	0.40	Likely Benign	0.256	Likely Benign	-4.59	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	3.40	Benign	0.02	Affected			0.2875	0.1126		1	0	0.4	-14.07
c.1924A>C	K642Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K642Q is not reported in ClinVar and has no allele in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and polyPhen‑2 HumVar; pathogenic predictions come from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. No other high‑confidence predictions are available. Overall, the balance of evidence leans toward a benign effect, with the single high‑accuracy pathogenic signal from SGM‑Consensus not contradicting the lack of ClinVar annotation. Thus, the variant is most likely benign, and this assessment does not conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-12.186	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	0.08	Likely Benign	0.0	0.17	Likely Benign	0.13	Likely Benign	0.42	Likely Benign	0.380	Likely Benign	-3.88	Deleterious	0.576	Possibly Damaging	0.383	Benign	2.87	Benign	0.02	Affected			0.4477	0.1253		1	1	0.4	-0.04
c.1924A>G	K642E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K642E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized). High‑accuracy methods give a mixed signal: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. No prediction is inconclusive. Overall, the majority of tools lean toward pathogenicity, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.287	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	0.26	Likely Benign	0.1	-0.13	Likely Benign	0.07	Likely Benign	0.40	Likely Benign	0.404	Likely Benign	-3.92	Deleterious	0.116	Benign	0.011	Benign	2.96	Benign	0.03	Affected			0.3865	0.1013		0	1	0.4	0.94
c.1926G>C	K642N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K642N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and polyPhen‑2 HumVar. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. With two of the three high‑accuracy tools supporting pathogenicity and an overall balance of predictions, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.423	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.05	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.273	Likely Benign	-4.88	Deleterious	0.958	Probably Damaging	0.392	Benign	2.88	Benign	0.00	Affected			0.3553	0.1590		1	0	0.4	-14.07
c.1926G>T	K642N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K642N 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, and FATHMM, while those that predict a pathogenic impact are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen‑2 HumVar (benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign. Overall, seven tools favor pathogenicity versus six favoring benign, and the high‑accuracy predictions are mixed. Thus, the variant is most likely pathogenic based on the preponderance 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	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000											-11.423	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.25	Likely Benign	0.0	0.05	Likely Benign	0.15	Likely Benign	0.48	Likely Benign	0.274	Likely Benign	-4.88	Deleterious	0.958	Probably Damaging	0.392	Benign	2.88	Benign	0.00	Affected			0.3553	0.1590		1	0	0.4	-14.07
c.1936C>G	L646V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L646V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized, and FATHMM, whereas pathogenic predictions arise from FoldX, Rosetta, premPS, SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to “Likely Benign” (3 benign vs 1 pathogenic votes). High‑accuracy assessments further indicate AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, lean toward a benign 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	GAP	0.048328	Structured	0.303751	Uncertain	0.941	0.344	0.000											-8.995	Likely Pathogenic	0.332	Likely Benign	Likely Benign	3.82	Destabilizing	0.2	2.01	Destabilizing	2.92	Destabilizing	1.41	Destabilizing	0.125	Likely Benign	-1.40	Neutral	0.040	Benign	0.021	Benign	3.21	Benign	0.03	Affected			0.2200	0.3767		2	1	0.4	-14.03
c.1957C>G	L653V 2D AIThe SynGAP1 missense variant L653V is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, and premPS, while ESM1b is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.049374	Structured	0.335213	Uncertain	0.963	0.332	0.000					Uncertain		1				-7.050	In-Between	0.301	Likely Benign	Likely Benign	3.28	Destabilizing	0.3	2.18	Destabilizing	2.73	Destabilizing	1.32	Destabilizing	0.146	Likely Benign	-2.25	Neutral	0.227	Benign	0.039	Benign	3.28	Benign	0.08	Tolerated			0.1436	0.3557		2	1	0.4	-14.03
c.1963C>G	L655V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655V 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. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, SGM‑Consensus indicates likely benign, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. No tools predict pathogenicity, and the uncertain stability assessment does not alter the overall benign inference. Therefore, based on the available 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	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000											-6.743	Likely Benign	0.127	Likely Benign	Likely Benign	0.78	Ambiguous	0.0	0.58	Ambiguous	0.68	Ambiguous	0.38	Likely Benign	0.058	Likely Benign	-0.62	Neutral	0.008	Benign	0.003	Benign	3.45	Benign	0.44	Tolerated			0.1551	0.3190		2	1	0.4	-14.03
c.1990T>G	L664V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L664V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta and Foldetta are uncertain, providing no definitive evidence. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic (3 pathogenic vs 1 benign). Foldetta’s stability prediction is uncertain. Overall, the majority of reliable tools predict a pathogenic impact. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.100716	Structured	0.089318	Uncertain	0.937	0.339	0.000											-11.515	Likely Pathogenic	0.755	Likely Pathogenic	Likely Benign	2.01	Destabilizing	0.1	1.13	Ambiguous	1.57	Ambiguous	1.37	Destabilizing	0.378	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.776	Possibly Damaging	2.91	Benign	0.01	Affected			0.0984	0.2628		2	1	0.4	-14.03
c.199C>G	L67V 2D AIThe SynGAP1 missense variant L67V 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the L67V substitution, 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		0.458154	Structured	0.473668	Uncertain	0.428	0.761	0.125											-3.617	Likely Benign	0.285	Likely Benign	Likely Benign										0.122	Likely Benign	-0.31	Neutral	0.458	Possibly Damaging	0.364	Benign	4.15	Benign	0.00	Affected			0.1138	0.2817		2	1	0.4	-14.03
c.2008C>G	L670V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L670V 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, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all indicate benign. Only ESM1b predicts pathogenicity, while FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta remains uncertain. Taken together, the overwhelming majority of evidence supports a benign interpretation, and this conclusion does not conflict with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000											-9.829	Likely Pathogenic	0.113	Likely Benign	Likely Benign	1.45	Ambiguous	0.1	1.05	Ambiguous	1.25	Ambiguous	0.15	Likely Benign	0.025	Likely Benign	-0.60	Neutral	0.127	Benign	0.023	Benign	3.67	Benign	0.74	Tolerated			0.1558	0.4108		2	1	0.4	-14.03
c.2017C>G	L673V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673V is 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, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Benign, and Foldetta as pathogenic, yielding one pathogenic versus two benign predictions. 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.	Likely Benign	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-8.132	Likely Pathogenic	0.099	Likely Benign	Likely Benign	2.18	Destabilizing	0.3	2.10	Destabilizing	2.14	Destabilizing	0.10	Likely Benign	0.017	Likely Benign	-0.58	Neutral	0.016	Benign	0.003	Benign	3.36	Benign	0.28	Tolerated			0.1448	0.3777		2	1	0.4	-14.03
c.2026A>G	S676G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S676G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and SIFT. Two tools (ESM1b and premPS) returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta predicts a benign stability change. No prediction or folding result is missing or inconclusive. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.209395	Structured	0.113632	Uncertain	0.551	0.338	0.125											-7.249	In-Between	0.117	Likely Benign	Likely Benign	0.38	Likely Benign	0.1	0.25	Likely Benign	0.32	Likely Benign	0.67	Ambiguous	0.132	Likely Benign	-2.74	Deleterious	0.855	Possibly Damaging	0.100	Benign	3.39	Benign	0.02	Affected			0.2772	0.4342		1	0	0.4	-30.03
c.2029A>G	S677G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. Predictions that are inconclusive—FoldX, Rosetta, Foldetta, and premPS—are treated as unavailable. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates benign; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the evidence supports a benign classification for S677G, and this conclusion does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125											-5.126	Likely Benign	0.060	Likely Benign	Likely Benign	0.98	Ambiguous	0.1	1.20	Ambiguous	1.09	Ambiguous	0.64	Ambiguous	0.126	Likely Benign	-1.38	Neutral	0.002	Benign	0.001	Benign	3.30	Benign	0.26	Tolerated			0.2885	0.5325		1	0	0.4	-30.03
c.202C>G	L68V 2D AIThe SynGAP1 missense variant L68V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those 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 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 points to a benign 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 Benign		0.534167	Disordered	0.470567	Uncertain	0.405	0.768	0.250											-4.079	Likely Benign	0.470	Ambiguous	Likely Benign										0.028	Likely Benign	-0.43	Neutral	0.458	Possibly Damaging	0.364	Benign	4.13	Benign	0.00	Affected			0.1077	0.2817		2	1	0.4	-14.03
c.2032A>G	S678G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S678G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, REVEL, FoldX, premPS, and Foldetta. No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is listed as “Uncertain.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.301917	Structured	0.123585	Uncertain	0.660	0.321	0.000											-4.379	Likely Benign	0.069	Likely Benign	Likely Benign	0.24	Likely Benign	0.2	0.55	Ambiguous	0.40	Likely Benign	-0.24	Likely Benign	0.082	Likely Benign	1.90	Neutral	0.000	Benign	0.001	Benign	3.43	Benign	1.00	Tolerated			0.2807	0.4961		1	0	0.4	-30.03
c.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.2065C>G	L689V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) and the SGM Consensus (Likely Pathogenic) predict a pathogenic impact. The high‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM Consensus is Likely Pathogenic; Foldetta predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for L689V. This conclusion is not contradicted by ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-11.387	Likely Pathogenic	0.862	Likely Pathogenic	Ambiguous	2.98	Destabilizing	0.1	2.25	Destabilizing	2.62	Destabilizing	1.32	Destabilizing	0.234	Likely Benign	-2.97	Deleterious	0.926	Possibly Damaging	0.481	Possibly Damaging	3.27	Benign	0.00	Affected			0.1393	0.3189		2	1	0.4	-14.03
c.2074C>G	L692V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692V is not 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, Rosetta, 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 pathogenic, and Foldetta also predicts pathogenic. No predictions are missing or inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000											-11.441	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	3.29	Destabilizing	0.1	2.91	Destabilizing	3.10	Destabilizing	1.57	Destabilizing	0.286	Likely Benign	-2.99	Deleterious	0.978	Probably Damaging	0.606	Possibly Damaging	3.12	Benign	0.01	Affected			0.1395	0.2460		2	1	0.4	-14.03
c.2083C>G	L695V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. FoldX, Rosetta, and Foldetta give uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs. 2 pathogenic), and Foldetta is also unavailable. Overall, the majority of available predictions (six pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-10.605	Likely Pathogenic	0.317	Likely Benign	Likely Benign	1.61	Ambiguous	0.0	1.57	Ambiguous	1.59	Ambiguous	1.19	Destabilizing	0.274	Likely Benign	-2.99	Deleterious	0.993	Probably Damaging	0.694	Possibly Damaging	3.20	Benign	0.02	Affected			0.1158	0.2828		2	1	0.4	-14.03
c.2086C>G	L696V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696V variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) report a pathogenic outcome; Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for the variant, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000					Uncertain		1				-11.909	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	2.35	Destabilizing	0.1	1.85	Ambiguous	2.10	Destabilizing	1.46	Destabilizing	0.351	Likely Benign	-2.79	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected	3.46	13	0.1307	0.2830		1	2	0.4	-14.03
c.2098C>G	L700V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L700V 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. In contrast, protein‑stability methods predict a deleterious impact: FoldX and Rosetta both score the variant as pathogenic, and the combined Foldetta analysis (FoldX‑MD + Rosetta) also reports a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta remains pathogenic. Overall, the majority of predictions support 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	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000											-3.703	Likely Benign	0.192	Likely Benign	Likely Benign	2.52	Destabilizing	0.0	3.16	Destabilizing	2.84	Destabilizing	0.13	Likely Benign	0.056	Likely Benign	0.37	Neutral	0.003	Benign	0.005	Benign	3.46	Benign	0.76	Tolerated			0.1424	0.2460		2	1	0.4	-14.03
c.2107C>G	L703V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703V is 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Because the variant is not present in ClinVar or gnomAD, there is no existing clinical classification to contradict. Overall, the majority of predictions and the two high‑accuracy benign assessments suggest the variant is most likely benign, although the Foldetta result indicates a potential pathogenic effect that warrants further functional investigation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-10.086	Likely Pathogenic	0.301	Likely Benign	Likely Benign	2.32	Destabilizing	0.1	2.61	Destabilizing	2.47	Destabilizing	1.07	Destabilizing	0.080	Likely Benign	-2.22	Neutral	0.789	Possibly Damaging	0.352	Benign	3.19	Benign	0.00	Affected			0.1383	0.2621		2	1	0.4	-14.03
c.2110A>G	S704G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S704G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Taken together, the majority of reliable predictors indicate a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.096677	Structured	0.383620	Uncertain	0.928	0.363	0.000											-7.827	In-Between	0.169	Likely Benign	Likely Benign	1.05	Ambiguous	0.1	1.33	Ambiguous	1.19	Ambiguous	0.53	Ambiguous	0.091	Likely Benign	-2.25	Neutral	0.981	Probably Damaging	0.514	Possibly Damaging	3.42	Benign	0.07	Tolerated			0.2224	0.3378		1	0	0.4	-30.03
c.2113A>C	K705Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K705Q missense variant (ClinVar ID 3699560.0) is listed as “Uncertain” in ClinVar and is present in gnomAD (variant ID 6‑33441372‑A‑C). Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (uncertain), ESM1b (benign), FATHMM (benign), and PROVEAN (benign)—also yields a benign classification; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the preponderance of evidence supports a benign impact for K705Q, and this conclusion does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000					Uncertain		1	6-33441372-A-C	1	6.20e-7	-5.787	Likely Benign	0.436	Ambiguous	Likely Benign	-0.10	Likely Benign	0.0	0.33	Likely Benign	0.12	Likely Benign	-0.02	Likely Benign	0.142	Likely Benign	-0.24	Neutral	0.997	Probably Damaging	0.969	Probably Damaging	3.42	Benign	0.78	Tolerated	3.47	10	0.3063	0.1014		1	1	0.4	-0.04
c.2113A>G	K705E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K705E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, AlphaMissense‑Optimized, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta predicts a benign stability change. Overall, the majority of evidence (9 benign vs. 4 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	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000											-9.371	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.10	Likely Benign	0.0	-0.09	Likely Benign	0.01	Likely Benign	0.47	Likely Benign	0.075	Likely Benign	-1.53	Neutral	0.935	Possibly Damaging	0.537	Possibly Damaging	3.33	Benign	0.14	Tolerated			0.2601	0.0789		0	1	0.4	0.94
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.2122C>G	L708V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708V 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results are from FoldX (uncertain) and Foldetta (uncertain). High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta remains uncertain. Overall, the evidence strongly indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-4.361	Likely Benign	0.097	Likely Benign	Likely Benign	1.59	Ambiguous	0.0	0.12	Likely Benign	0.86	Ambiguous	-0.02	Likely Benign	0.122	Likely Benign	-0.23	Neutral	0.158	Benign	0.035	Benign	3.35	Benign	0.94	Tolerated			0.1094	0.2460		2	1	0.4	-14.03
c.2125C>G	L709V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L709V is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool that produced a definitive call classifies the variant as benign: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. No tool predicts pathogenicity. The only inconclusive results are FoldX (uncertain) and Foldetta (uncertain), which are treated as unavailable evidence. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign; the SGM‑Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is also benign; Foldetta remains uncertain. Consequently, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.243554	Structured	0.365830	Uncertain	0.934	0.379	0.000											-4.406	Likely Benign	0.101	Likely Benign	Likely Benign	0.75	Ambiguous	0.0	0.42	Likely Benign	0.59	Ambiguous	0.03	Likely Benign	0.063	Likely Benign	-0.36	Neutral	0.062	Benign	0.016	Benign	3.42	Benign	0.45	Tolerated			0.1162	0.2460		2	1	0.4	-14.03
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.2128A>G	K710E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K710E missense variant is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, SIFT, and FATHMM, while pathogenic predictions arise from SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.321458	Structured	0.370438	Uncertain	0.949	0.368	0.000											-11.405	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.56	Ambiguous	0.0	0.94	Ambiguous	0.75	Ambiguous	0.39	Likely Benign	0.178	Likely Benign	-3.53	Deleterious	0.998	Probably Damaging	0.991	Probably Damaging	3.45	Benign	0.08	Tolerated			0.2655	0.0789		0	1	0.4	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.2131C>G	L711V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L711V is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441596‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000					Uncertain		1	6-33441596-C-G	1	6.20e-7	-10.045	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	3.48	Destabilizing	0.1	2.22	Destabilizing	2.85	Destabilizing	1.40	Destabilizing	0.170	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.34	Benign	0.00	Affected	3.50	9	0.1318	0.3010		1	2	0.4	-14.03
c.2140C>G	L714V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L714V has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect include FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Overall, the majority of predictions (10 pathogenic vs. 4 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, which has no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.314870	Structured	0.402311	Uncertain	0.961	0.369	0.000											-4.966	Likely Benign	0.781	Likely Pathogenic	Likely Benign	3.91	Destabilizing	0.1	6.19	Destabilizing	5.05	Destabilizing	1.21	Destabilizing	0.259	Likely Benign	-2.76	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected			0.1421	0.2689		2	1	0.4	-14.03
c.2149C>G	L717V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717V 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 score (Likely Benign). Two tools predict a damaging effect: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Stability‑based methods (FoldX, Rosetta, Foldetta) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as inconclusive. Taken together, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000											-6.164	Likely Benign	0.308	Likely Benign	Likely Benign	1.53	Ambiguous	0.0	1.25	Ambiguous	1.39	Ambiguous	0.09	Likely Benign	0.119	Likely Benign	-0.25	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.38	Benign	0.51	Tolerated			0.1226	0.2489		2	1	0.4	-14.03
c.2152C>G	L718V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and AlphaMissense‑Optimized, whereas the remaining tools (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized reports benign, the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, 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	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-11.585	Likely Pathogenic	0.693	Likely Pathogenic	Likely Benign	3.15	Destabilizing	0.1	2.11	Destabilizing	2.63	Destabilizing	1.14	Destabilizing	0.237	Likely Benign	-2.83	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.36	Pathogenic	0.00	Affected			0.1485	0.2656		2	1	0.4	-14.03
c.2164A>G	S722G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722G is not reported in ClinVar and is present in gnomAD (ID 6‑33441629‑A‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and the protein‑folding stability method Foldetta. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as benign. No evidence from the high‑accuracy tools contradicts the benign predictions, but the consensus and several individual pathogenic predictors suggest a potential deleterious impact. Based on the overall pattern of predictions, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and the presence of multiple pathogenic signals. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375								6-33441629-A-G	2	1.24e-6	-9.141	Likely Pathogenic	0.214	Likely Benign	Likely Benign	0.24	Likely Benign	0.1	0.67	Ambiguous	0.46	Likely Benign	0.50	Likely Benign	0.270	Likely Benign	-2.72	Deleterious	0.998	Probably Damaging	0.863	Possibly Damaging	2.49	Pathogenic	0.14	Tolerated	3.50	8	0.2202	0.3400		0	1	0.4	-30.03
c.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.2203A>G	S735G 2D AIThe SynGAP1 missense variant S735G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the majority of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.916840	Disordered	0.412174	Uncertain	0.290	0.752	0.875											-5.986	Likely Benign	0.083	Likely Benign	Likely Benign										0.097	Likely Benign	-0.55	Neutral	0.953	Possibly Damaging	0.744	Possibly Damaging	2.68	Benign	0.23	Tolerated			0.2777	0.4089		1	0	0.4	-30.03
c.220A>G	S74G 2D AIThe SynGAP1 missense variant S74G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.450156	Uncertain	0.294	0.831	0.500											-3.540	Likely Benign	0.071	Likely Benign	Likely Benign										0.028	Likely Benign	-1.30	Neutral	0.000	Benign	0.000	Benign	4.08	Benign	0.00	Affected			0.2347	0.3749		1	0	0.4	-30.03
c.2212A>G	S738G 2D AIThe SynGAP1 missense variant S738G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.441162	Uncertain	0.284	0.827	0.875											-3.863	Likely Benign	0.053	Likely Benign	Likely Benign										0.055	Likely Benign	-1.53	Neutral	0.002	Benign	0.003	Benign	2.66	Benign	0.01	Affected			0.2032	0.3385		1	0	0.4	-30.03
c.2242C>G	L748V 2D AIThe SynGAP1 missense variant L748V is not reported 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		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750											-3.454	Likely Benign	0.078	Likely Benign	Likely Benign										0.045	Likely Benign	-0.42	Neutral	0.679	Possibly Damaging	0.216	Benign	2.74	Benign	0.05	Affected			0.1680	0.3485		2	1	0.4	-14.03
c.2287C>G	L763V 2D AIThe SynGAP1 missense variant L763V 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 outcome, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.918636	Binding	0.351	0.865	0.125											-5.138	Likely Benign	0.164	Likely Benign	Likely Benign										0.027	Likely Benign	-0.94	Neutral	0.573	Possibly Damaging	0.230	Benign	2.57	Benign	0.25	Tolerated			0.1548	0.2817		2	1	0.4	-14.03
c.2293A>G	S765G 2D AIThe SynGAP1 missense variant S765G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to the variant being most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.370445	Structured	0.922652	Binding	0.335	0.865	0.250											-4.658	Likely Benign	0.152	Likely Benign	Likely Benign										0.048	Likely Benign	-0.98	Neutral	0.963	Probably Damaging	0.950	Probably Damaging	4.09	Benign	0.05	Affected			0.2894	0.4946		1	0	0.4	-30.03
c.229A>G	S77G 2D AIThe SynGAP1 missense variant S77G is reported in gnomAD (variant ID 6‑33425837‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact for S77G. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.490133	Structured	0.446124	Uncertain	0.310	0.855	0.375								6-33425837-A-G	2	1.24e-6	-3.571	Likely Benign	0.064	Likely Benign	Likely Benign										0.014	Likely Benign	-1.23	Neutral	0.022	Benign	0.003	Benign	4.09	Benign	0.00	Affected	4.32	1	0.2204	0.3866		0	1	0.4	-30.03
c.2305C>G	L769V 2D AIThe SynGAP1 missense variant L769V 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 flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that 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		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250											-4.585	Likely Benign	0.106	Likely Benign	Likely Benign										0.075	Likely Benign	-0.41	Neutral	0.625	Possibly Damaging	0.249	Benign	4.04	Benign	0.25	Tolerated			0.1364	0.2558		2	1	0.4	-14.03
c.2329C>G	L777V 2D AIThe SynGAP1 missense variant L777V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250											-5.693	Likely Benign	0.134	Likely Benign	Likely Benign										0.084	Likely Benign	-1.05	Neutral	0.843	Possibly Damaging	0.920	Probably Damaging	4.07	Benign	0.05	Affected			0.1651	0.3977		2	1	0.4	-14.03
c.2335A>G	S779G 2D AIThe SynGAP1 missense variant S779G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375											-4.304	Likely Benign	0.111	Likely Benign	Likely Benign										0.103	Likely Benign	0.38	Neutral	0.393	Benign	0.324	Benign	2.65	Benign	0.53	Tolerated			0.2894	0.5087		1	0	0.4	-30.03
c.2356C>G	L786V 2D AIThe SynGAP1 missense variant L786V is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently has no classification for L786V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-4.607	Likely Benign	0.310	Likely Benign	Likely Benign										0.099	Likely Benign	-1.66	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.00	Pathogenic	0.00	Affected			0.1683	0.4049		2	1	0.4	-14.03
c.2371A>C	K791Q 2D AIThe SynGAP1 missense variant K791Q 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 flags the variant as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that K791Q is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-3.418	Likely Benign	0.195	Likely Benign	Likely Benign										0.081	Likely Benign	-0.09	Neutral	0.802	Possibly Damaging	0.335	Benign	4.17	Benign	0.46	Tolerated			0.5322	0.1159	Weaken	1	1	0.4	-0.04
c.2371A>G	K791E 2D AIThe SynGAP1 missense variant K791E is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly favor a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) indicates likely benign; Foldetta results are unavailable. Taken together, the preponderance of evidence supports a benign impact for K791E, 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	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-3.823	Likely Benign	0.465	Ambiguous	Likely Benign										0.053	Likely Benign	-0.58	Neutral	0.451	Benign	0.193	Benign	4.22	Benign	0.65	Tolerated			0.4829	0.0876		0	1	0.4	0.94
c.2373G>C	K791N 2D AIThe SynGAP1 missense variant K791N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑accuracy predictions (SGM‑Consensus, AlphaMissense‑Optimized uncertain, Foldetta unavailable) lean toward a benign interpretation, with only two pathogenic calls. Thus, based on the current computational 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	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-4.001	Likely Benign	0.794	Likely Pathogenic	Ambiguous										0.027	Likely Benign	-1.26	Neutral	0.666	Possibly Damaging	0.267	Benign	4.14	Benign	0.13	Tolerated			0.4578	0.1354		1	0	0.4	-14.07
c.2373G>T	K791N 2D AIThe SynGAP1 missense variant K791N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. 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 predictions (including the SGM‑Consensus) indicate a benign impact, and there is no conflict with ClinVar status. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.966441	Disordered	0.478670	Uncertain	0.356	0.896	0.875											-4.001	Likely Benign	0.794	Likely Pathogenic	Ambiguous										0.027	Likely Benign	-1.26	Neutral	0.666	Possibly Damaging	0.267	Benign	4.14	Benign	0.13	Tolerated			0.4578	0.1354		1	0	0.4	-14.07
c.2377A>C	K793Q 2D AIThe SynGAP1 missense variant K793Q is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign status. Foldetta results are unavailable, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-2.838	Likely Benign	0.256	Likely Benign	Likely Benign										0.032	Likely Benign	-0.83	Neutral	0.174	Benign	0.099	Benign	4.13	Benign	0.06	Tolerated			0.5276	0.1540	Weaken	1	1	0.4	-0.04
c.2377A>G	K793E 2D AIThe SynGAP1 missense variant K793E is listed in gnomAD (ID 6‑33442929‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875								6-33442929-A-G			-4.233	Likely Benign	0.555	Ambiguous	Likely Benign										0.035	Likely Benign	-1.05	Neutral	0.001	Benign	0.006	Benign	4.17	Benign	0.05	Affected	4.07	3	0.4670	0.1499		1	0	0.4	0.94
c.2379G>C	K793N 2D AIThe SynGAP1 missense variant K793N is catalogued in gnomAD (6‑33442931‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify it as benign, and the SGM‑Consensus score (Likely Benign) supports this view. Only AlphaMissense‑Default predicts pathogenicity. High‑accuracy assessments further reinforce the benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification. 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 K793N 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	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875								6-33442931-G-C	4	2.48e-6	-5.162	Likely Benign	0.632	Likely Pathogenic	Likely Benign										0.040	Likely Benign	1.18	Neutral	0.174	Benign	0.135	Benign	4.13	Benign	0.47	Tolerated	4.07	3	0.4429	0.1976		0	1	0.4	-14.07
c.2379G>T	K793N 2D AIThe SynGAP1 missense variant K793N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only AlphaMissense‑Default predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.971072	Disordered	0.426071	Uncertain	0.344	0.901	0.875											-5.162	Likely Benign	0.632	Likely Pathogenic	Likely Benign										0.040	Likely Benign	1.18	Neutral	0.174	Benign	0.135	Benign	4.13	Benign	0.47	Tolerated	4.07	3	0.4429	0.1976		0	1	0.4	-14.07
c.238A>C	K80Q 2D AIThe SynGAP1 missense variant K80Q 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, 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. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-4.475	Likely Benign	0.662	Likely Pathogenic	Likely Benign										0.064	Likely Benign	-0.81	Neutral	0.414	Benign	0.040	Benign	3.93	Benign	0.00	Affected			0.4373	0.1132		1	1	0.4	-0.04
c.238A>G	K80E 2D AIThe SynGAP1 K80E missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Overall, the balance of evidence favors a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for K80E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.605	Likely Benign	0.943	Likely Pathogenic	Ambiguous										0.034	Likely Benign	-0.91	Neutral	0.225	Benign	0.027	Benign	3.92	Benign	0.00	Affected			0.3850	0.0952		0	1	0.4	0.94
c.2407A>C	K803Q 2D AIThe SynGAP1 missense variant K803Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of high‑confidence predictions lean toward a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-2.792	Likely Benign	0.305	Likely Benign	Likely Benign										0.108	Likely Benign	-2.01	Neutral	0.984	Probably Damaging	0.773	Possibly Damaging	2.36	Pathogenic	0.00	Affected			0.4810	0.1398		1	1	0.4	-0.04
c.2407A>G	K803E 2D AIThe SynGAP1 missense variant K803E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs 2 benign) and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) predict a pathogenic impact. Thus, the variant is most likely pathogenic, and this prediction does not contradict any ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-3.889	Likely Benign	0.650	Likely Pathogenic	Likely Benign										0.172	Likely Benign	-2.06	Neutral	0.896	Possibly Damaging	0.596	Possibly Damaging	2.38	Pathogenic	0.00	Affected			0.4043	0.1357		0	1	0.4	0.94
c.2409A>C	K803N 2D AIThe SynGAP1 K803N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, 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 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, more tools predict pathogenicity (five) than benignity (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.039	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-2.13	Neutral	0.896	Possibly Damaging	0.673	Possibly Damaging	2.34	Pathogenic	0.00	Affected			0.3805	0.2035		1	0	0.4	-14.07
c.2409A>T	K803N 2D AIThe SynGAP1 K803N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that 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 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, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy assessments do not overturn this trend. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.827927	Disordered	0.733908	Binding	0.349	0.900	0.625											-5.039	Likely Benign	0.807	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-2.13	Neutral	0.896	Possibly Damaging	0.673	Possibly Damaging	2.34	Pathogenic	0.00	Affected			0.3805	0.2035		1	0	0.4	-14.07
c.240A>C	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.240A>T	K80N 2D AIThe SynGAP1 K80N missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) remains benign; Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.477530	Uncertain	0.331	0.873	0.500											-5.072	Likely Benign	0.958	Likely Pathogenic	Likely Pathogenic										0.078	Likely Benign	-1.07	Neutral	0.588	Possibly Damaging	0.054	Benign	3.89	Benign	0.00	Affected			0.3749	0.1237		1	0	0.4	-14.07
c.2413C>G	L805V 2D AIThe SynGAP1 missense variant L805V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the conclusion. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625											-2.445	Likely Benign	0.094	Likely Benign	Likely Benign										0.027	Likely Benign	-1.16	Neutral	0.003	Benign	0.008	Benign	2.65	Benign	0.00	Affected			0.1553	0.3493		2	1	0.4	-14.03
c.241C>G	L81V 2D AIThe SynGAP1 missense variant L81V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence supports a benign classification for L81V, 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		0.632174	Disordered	0.502033	Binding	0.291	0.878	0.250											-5.207	Likely Benign	0.289	Likely Benign	Likely Benign										0.038	Likely Benign	-0.51	Neutral	0.178	Benign	0.014	Benign	4.04	Benign	0.00	Affected			0.1423	0.2653		2	1	0.4	-14.03
c.2425A>G	S809G 2D AIThe SynGAP1 missense variant S809G is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the conclusion. Overall, the preponderance of evidence indicates that S809G is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500											-6.100	Likely Benign	0.142	Likely Benign	Likely Benign										0.085	Likely Benign	-1.80	Neutral	0.270	Benign	0.136	Benign	2.61	Benign	0.02	Affected			0.2743	0.5369		1	0	0.4	-30.03
c.2437C>G	L813V 2D AIThe SynGAP1 missense variant L813V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250											-4.809	Likely Benign	0.215	Likely Benign	Likely Benign										0.136	Likely Benign	-0.98	Neutral	0.994	Probably Damaging	0.856	Possibly Damaging	2.62	Benign	0.28	Tolerated			0.1704	0.3744		2	1	0.4	-14.03
c.244C>G	L82V 2D AIThe SynGAP1 missense variant L82V is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (ID 6‑33425852‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are SIFT and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and no Foldetta stability result is available. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments therefore indicate a benign likelihood: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus is likely benign, and Foldetta data are missing. Overall, the majority of predictions support a benign impact, 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		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375								6-33425852-C-G			-6.701	Likely Benign	0.914	Likely Pathogenic	Ambiguous										0.065	Likely Benign	-1.13	Neutral	0.371	Benign	0.024	Benign	3.72	Benign	0.00	Affected	4.32	1	0.1467	0.2353		1	2	0.4	-14.03
c.2467A>G	S823G 2D AIThe SynGAP1 missense variant S823G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and the Foldetta stability analysis is unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750											-6.034	Likely Benign	0.822	Likely Pathogenic	Ambiguous										0.202	Likely Benign	-2.59	Deleterious	0.992	Probably Damaging	0.987	Probably Damaging	1.96	Pathogenic	0.00	Affected			0.2855	0.5287		1	0	0.4	-30.03
c.2470A>G	S824G 2D AIThe SynGAP1 missense variant S824G is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33443022‑A‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Based on the preponderance of benign predictions and the consensus from high‑accuracy tools, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750								6-33443022-A-G	1	6.20e-7	-5.476	Likely Benign	0.543	Ambiguous	Likely Benign										0.079	Likely Benign	-1.74	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.60	Benign	0.50	Tolerated	3.77	5	0.2880	0.5437		0	1	0.4	-30.03
c.2497A>C	K833Q 2D AIThe SynGAP1 missense variant K833Q 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. 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 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 stability analysis is unavailable. Overall, the consensus of most evidence points to a benign effect, 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		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-1.586	Likely Benign	0.215	Likely Benign	Likely Benign										0.105	Likely Benign	-0.34	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.62	Benign	0.68	Tolerated			0.3744	0.1219		1	1	0.4	-0.04
c.2497A>G	K833E 2D AIThe SynGAP1 missense variant K833E is evaluated by multiple in silico tools. Benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The AlphaMissense‑Default score is uncertain. The consensus predictor 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, SGM‑Consensus confirms Likely Benign, and Foldetta data are not available. ClinVar contains no entry for this variant, and it is absent from gnomAD, so no external evidence contradicts the computational assessment. Based on the collective predictions, the variant is most likely benign, with no conflict from ClinVar status. 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											-2.495	Likely Benign	0.506	Ambiguous	Likely Benign										0.108	Likely Benign	-0.69	Neutral	0.997	Probably Damaging	0.925	Probably Damaging	2.72	Benign	0.04	Affected			0.3162	0.1039		0	1	0.4	0.94
c.2499G>C	K833N 2D AIThe SynGAP1 missense variant K833N is 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 balance of evidence favors a benign interpretation. This conclusion is consistent with the lack of a ClinVar assertion, 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		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-2.759	Likely Benign	0.579	Likely Pathogenic	Likely Benign										0.087	Likely Benign	-1.02	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.61	Benign	0.02	Affected			0.3088	0.1464		1	0	0.4	-14.07
c.2499G>T	K833N 2D AIThe SynGAP1 missense variant K833N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for K833N, 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		0.671169	Disordered	0.625797	Binding	0.315	0.863	0.375											-2.759	Likely Benign	0.579	Likely Pathogenic	Likely Benign										0.087	Likely Benign	-1.02	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.61	Benign	0.02	Affected			0.3088	0.1464		1	0	0.4	-14.07
c.2503C>G	L835V 2D AIThe SynGAP1 missense variant L835V is reported in gnomAD (variant ID 6‑33443055‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict the variant to be pathogenic. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools indicates that 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		0.608892	Disordered	0.642742	Binding	0.319	0.863	0.125								6-33443055-C-G	1	6.19e-7	-3.439	Likely Benign	0.115	Likely Benign	Likely Benign										0.073	Likely Benign	-0.70	Neutral	0.995	Probably Damaging	0.926	Probably Damaging	2.72	Benign	0.17	Tolerated	3.77	5	0.1492	0.2886		1	2	0.4	-14.03
c.2506A>G	S836G 2D AIThe SynGAP1 missense variant S836G is listed in ClinVar (ID 537003.0) with an uncertain significance annotation and is observed in the gnomAD database (variant ID 6‑33443058‑A‑G). Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Benign. Foldetta, a protein‑folding stability predictor, did not return a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports a benign classification, which does not conflict with the ClinVar uncertain designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.634582	Binding	0.269	0.859	0.250					Uncertain		1	6-33443058-A-G	4	2.48e-6	-4.749	Likely Benign	0.112	Likely Benign	Likely Benign										0.066	Likely Benign	-1.65	Neutral	0.006	Benign	0.019	Benign	2.54	Benign	0.39	Tolerated	3.77	5	0.2567	0.4089		1	0	0.4	-30.03
c.2515A>C	K839Q 2D AIThe SynGAP1 missense variant K839Q is not reported 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 AlphaMissense‑Optimized, whereas tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and the Foldetta stability analysis is unavailable. Overall, the majority of predictions and the consensus call indicate a pathogenic 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.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.631	Likely Pathogenic	0.694	Likely Pathogenic	Likely Benign										0.162	Likely Benign	-1.98	Neutral	0.972	Probably Damaging	0.862	Possibly Damaging	2.47	Pathogenic	0.02	Affected			0.4544	0.1437		1	1	0.4	-0.04
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.2517G>C	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated predictors—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico tools indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2517G>T	K839N 2D AIThe SynGAP1 missense variant K839N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized returns a pathogenic score, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that K839N is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375											-10.939	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.94	Deleterious	0.996	Probably Damaging	0.951	Probably Damaging	2.44	Pathogenic	0.01	Affected			0.3629	0.1876		1	0	0.4	-14.07
c.2518A>G	S840G 2D AIThe SynGAP1 missense variant S840G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, while the SGM‑Consensus remains Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect for S840G, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.622677	Disordered	0.611356	Binding	0.259	0.865	0.250											-8.117	Likely Pathogenic	0.674	Likely Pathogenic	Likely Benign										0.163	Likely Benign	-2.72	Deleterious	0.889	Possibly Damaging	0.663	Possibly Damaging	1.54	Pathogenic	0.00	Affected			0.2354	0.3858		1	0	0.4	-30.03
c.2530C>G	L844V 2D AIThe SynGAP1 missense variant L844V 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		0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375											0.094	Likely Benign	0.240	Likely Benign	Likely Benign										0.043	Likely Benign	0.20	Neutral	0.409	Benign	0.253	Benign	2.87	Benign	0.62	Tolerated			0.1692	0.3744		2	1	0.4	-14.03
c.2536T>G	L846V 2D AIThe SynGAP1 missense variant L846V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Pathogenic, while AlphaMissense‑Optimized remains benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not conflict with any ClinVar annotation (none is present). 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											-8.326	Likely Pathogenic	0.569	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.07	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.20	Pathogenic	0.00	Affected			0.1540	0.3126		2	1	0.4	-14.03
c.2563C>G	L855V 2D AIThe SynGAP1 missense variant L855V 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. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-3.866	Likely Benign	0.077	Likely Benign	Likely Benign										0.086	Likely Benign	-0.71	Neutral	0.059	Benign	0.037	Benign	4.10	Benign	0.56	Tolerated			0.1621	0.3731		2	1	0.4	-14.03
c.2569A>G	S857G 2D AIThe SynGAP1 missense variant S857G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for S857G, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375											-4.316	Likely Benign	0.067	Likely Benign	Likely Benign										0.124	Likely Benign	-0.57	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	4.10	Benign	0.85	Tolerated			0.2963	0.5644		1	0	0.4	-30.03
c.2572A>G	S858G 2D AIThe SynGAP1 missense variant S858G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumVar indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also predicts benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375											-2.181	Likely Benign	0.068	Likely Benign	Likely Benign										0.143	Likely Benign	-0.18	Neutral	0.259	Benign	0.786	Possibly Damaging	4.13	Benign	0.11	Tolerated			0.3084	0.5116		1	0	0.4	-30.03
c.2575A>G	S859G 2D AIThe SynGAP1 missense variant S859G is not reported in ClinVar and is absent from gnomAD. In silico predictions cluster into three groups: benign (REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized), pathogenic (polyPhen‑2 HumDiv and HumVar), and uncertain (ESM1b). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for S859G, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375											-7.412	In-Between	0.087	Likely Benign	Likely Benign										0.118	Likely Benign	-0.69	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	4.00	Benign	0.25	Tolerated			0.2798	0.4988		1	0	0.4	-30.03
c.2587C>G	L863V 2D AIThe SynGAP1 missense variant L863V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for the L863V variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250											-3.651	Likely Benign	0.107	Likely Benign	Likely Benign										0.103	Likely Benign	-0.72	Neutral	0.995	Probably Damaging	0.926	Probably Damaging	4.09	Benign	0.21	Tolerated			0.1655	0.3544		2	1	0.4	-14.03
c.2605C>G	L869V 2D AIThe SynGAP1 missense variant L869V 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 is benign and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods 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		0.501700	Disordered	0.688653	Binding	0.272	0.839	0.250											-3.241	Likely Benign	0.161	Likely Benign	Likely Benign										0.093	Likely Benign	-0.33	Neutral	0.481	Possibly Damaging	0.300	Benign	2.86	Benign	0.11	Tolerated			0.1501	0.3616		2	1	0.4	-14.03
c.2608C>G	L870V 2D AIThe SynGAP1 missense variant L870V is listed in ClinVar (ID 946946.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, PolyPhen‑2 (HumDiv and HumVar) predict 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 for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not conflict with the ClinVar designation of uncertainty. 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					Uncertain		1				-4.123	Likely Benign	0.300	Likely Benign	Likely Benign										0.111	Likely Benign	-1.19	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.64	Benign	0.12	Tolerated	3.88	3	0.1549	0.3977		2	1	0.4	-14.03
c.2617A>G	S873G 2D AIThe SynGAP1 missense variant S873G is catalogued in gnomAD (ID 6‑33443169‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.414856	Structured	0.649816	Binding	0.283	0.866	0.125								6-33443169-A-G	4	2.48e-6	-5.702	Likely Benign	0.219	Likely Benign	Likely Benign										0.120	Likely Benign	-1.88	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.68	Benign	0.75	Tolerated	3.77	5	0.2897	0.5270		0	1	0.4	-30.03
c.2629C>G	L877V 2D AIThe SynGAP1 missense variant L877V is not reported in ClinVar and is absent from gnomAD. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign classification, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250											-5.063	Likely Benign	0.097	Likely Benign	Likely Benign										0.022	Likely Benign	-0.10	Neutral	0.232	Benign	0.109	Benign	2.71	Benign	0.26	Tolerated			0.1726	0.3178		2	1	0.4	-14.03
c.2641T>G	L881V 2D AIThe SynGAP1 missense variant L881V is not reported 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.629350	Binding	0.299	0.874	0.250											-3.961	Likely Benign	0.079	Likely Benign	Likely Benign										0.061	Likely Benign	-0.29	Neutral	0.790	Possibly Damaging	0.266	Benign	2.60	Benign	0.39	Tolerated			0.1599	0.3053		2	1	0.4	-14.03
c.2647C>G	L883V 2D AIThe SynGAP1 missense variant L883V 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—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.641952	Binding	0.334	0.886	0.250											-4.075	Likely Benign	0.079	Likely Benign	Likely Benign										0.059	Likely Benign	-0.28	Neutral	0.451	Benign	0.157	Benign	2.67	Benign	0.28	Tolerated			0.1611	0.3744		2	1	0.4	-14.03
c.2671C>G	L891V 2D AIThe SynGAP1 missense variant L891V 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 unavailable, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750											-4.992	Likely Benign	0.094	Likely Benign	Likely Benign										0.044	Likely Benign	-0.65	Neutral	0.057	Benign	0.032	Benign	2.72	Benign	0.70	Tolerated			0.1614	0.2945		2	1	0.4	-14.03
c.2683A>G	S895G 2D AIThe SynGAP1 missense variant S895G is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a benign outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750											-3.728	Likely Benign	0.150	Likely Benign	Likely Benign										0.149	Likely Benign	-1.25	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.67	Benign	0.90	Tolerated			0.2675	0.5087		1	0	0.4	-30.03
c.2716C>G	L906V 2D AIThe SynGAP1 missense variant L906V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a damaging or pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign consensus. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250											-5.105	Likely Benign	0.206	Likely Benign	Likely Benign										0.105	Likely Benign	-0.64	Neutral	0.981	Probably Damaging	0.832	Possibly Damaging	2.46	Pathogenic	0.21	Tolerated			0.1632	0.3744		2	1	0.4	-14.03
c.2719A>G	S907G 2D AIThe SynGAP1 missense variant S907G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250											-3.018	Likely Benign	0.151	Likely Benign	Likely Benign										0.078	Likely Benign	-1.23	Neutral	0.942	Possibly Damaging	0.788	Possibly Damaging	2.63	Benign	0.04	Affected			0.2625	0.5134		1	0	0.4	-30.03
c.2761C>G	L921V 2D AIThe SynGAP1 missense variant L921V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this conclusion, so the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375											-4.131	Likely Benign	0.221	Likely Benign	Likely Benign										0.045	Likely Benign	-1.03	Neutral	0.835	Possibly Damaging	0.524	Possibly Damaging	2.45	Pathogenic	0.27	Tolerated			0.1483	0.3178		2	1	0.4	-14.03
c.2773C>G	L925V 2D AIThe SynGAP1 missense variant L925V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools predict a pathogenic impact, and this prediction does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.483068	Structured	0.977963	Binding	0.290	0.852	0.125											-3.977	Likely Benign	0.831	Likely Pathogenic	Ambiguous										0.244	Likely Benign	-2.09	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.36	Pathogenic	0.00	Affected			0.1848	0.3230		2	1	0.4	-14.03
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.2947A>G	S983G 2D AIThe SynGAP1 missense variant S983G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 vs 2). High‑accuracy methods show AlphaMissense‑Optimized as benign; the SGM Consensus is unavailable, and Foldetta results are not provided, so no folding‑stability evidence is available. Overall, the balance of evidence (five pathogenic vs four benign predictions) suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625											-5.206	Likely Benign	0.638	Likely Pathogenic	Likely Benign										0.109	Likely Benign	-2.22	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.17	Pathogenic	0.00	Affected			0.2521	0.4480		1	0	0.4	-30.03
c.2950A>C	K984Q 2D AIThe SynGAP1 missense variant K984Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750											-2.932	Likely Benign	0.612	Likely Pathogenic	Likely Benign										0.083	Likely Benign	-0.67	Neutral	0.905	Possibly Damaging	0.637	Possibly Damaging	2.66	Benign	0.00	Affected			0.5054	0.1240	Weaken	1	1	0.4	-0.04
c.2950A>G	K984E 2D AIThe SynGAP1 missense variant K984E has no ClinVar record and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Overall, the majority of individual predictors lean toward benign, and the consensus score explicitly labels it benign, whereas a comparable number of tools predict pathogenicity. Based on the available evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750											-4.909	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.086	Likely Benign	-0.88	Neutral	0.798	Possibly Damaging	0.535	Possibly Damaging	2.71	Benign	0.00	Affected			0.4353	0.1200		0	1	0.4	0.94
c.2952G>C	K984N 2D AIThe SynGAP1 missense variant K984N is catalogued in gnomAD (6‑33443504‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized rates the variant as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign,” and Foldetta (which integrates FoldX‑MD and Rosetta outputs) has no available result for this residue. Overall, the balance of evidence leans toward a benign effect, with no pathogenic ClinVar classification to contradict this inference. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750								6-33443504-G-C	1	6.20e-7	-3.020	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.091	Likely Benign	0.52	Neutral	0.951	Possibly Damaging	0.637	Possibly Damaging	2.89	Benign	0.00	Affected	4.32	1	0.4138	0.1677		0	1	0.4	-14.07
c.2952G>T	K984N 2D AISynGAP1 missense variant K984N has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is Uncertain, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.951648	Binding	0.288	0.895	0.750											-3.020	Likely Benign	0.955	Likely Pathogenic	Ambiguous										0.091	Likely Benign	0.52	Neutral	0.951	Possibly Damaging	0.637	Possibly Damaging	2.89	Benign	0.00	Affected	4.32	1	0.4138	0.1677		0	1	0.4	-14.07
c.2953A>G	S985G 2D AIThe SynGAP1 missense variant S985G is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster into two groups: benign (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized) and pathogenic (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). The AlphaMissense‑Default score is uncertain, and Foldetta stability analysis is not available. High‑accuracy assessments show AlphaMissense‑Optimized predicting a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates a likely benign outcome. Foldetta, which integrates FoldX‑MD and Rosetta outputs, has no reported result for this variant. Overall, the majority of reliable predictors and the SGM‑Consensus support a benign classification. The variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750											-6.151	Likely Benign	0.546	Ambiguous	Likely Benign										0.132	Likely Benign	-2.29	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.51	Benign	0.00	Affected			0.2684	0.4540		1	0	0.4	-30.03
c.2962C>G	L988V 2D AIThe SynGAP1 missense variant L988V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for L988V, 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		0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750											-3.626	Likely Benign	0.226	Likely Benign	Likely Benign										0.096	Likely Benign	-1.42	Neutral	0.856	Possibly Damaging	0.474	Possibly Damaging	2.73	Benign	0.00	Affected			0.1652	0.3793		2	1	0.4	-14.03
c.2980A>C	K994Q 2D AIThe SynGAP1 missense variant K994Q 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		0.862302	Disordered	0.930054	Binding	0.289	0.912	0.750											-1.947	Likely Benign	0.124	Likely Benign	Likely Benign										0.105	Likely Benign	-0.45	Neutral	0.002	Benign	0.004	Benign	4.16	Benign	0.03	Affected			0.4975	0.1889		1	1	0.4	-0.04
c.2980A>G	K994E 2D AIThe SynGAP1 missense variant K994E is reported in gnomAD (variant ID 6‑33443532‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, points to a benign impact. This prediction 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		0.862302	Disordered	0.930054	Binding	0.289	0.912	0.750								6-33443532-A-G	1	6.20e-7	-2.587	Likely Benign	0.339	Likely Benign	Likely Benign										0.057	Likely Benign	-0.58	Neutral	0.036	Benign	0.039	Benign	4.14	Benign	0.02	Affected	4.32	2	0.4148	0.1699		1	0	0.4	0.94
c.2982G>C	K994N 2D AIThe SynGAP1 missense variant K994N 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, SGM‑Consensus confirms a Likely Benign status, and Foldetta data are unavailable. Taken together, the preponderance of evidence indicates that K994N 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		0.862302	Disordered	0.930054	Binding	0.289	0.912	0.750											-3.724	Likely Benign	0.519	Ambiguous	Likely Benign										0.011	Likely Benign	-0.73	Neutral	0.255	Benign	0.113	Benign	4.09	Benign	0.01	Affected			0.4010	0.2376		1	0	0.4	-14.07
c.2982G>T	K994N 2D AIThe SynGAP1 missense variant K994N 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, SGM‑Consensus confirms a Likely Benign status, and Foldetta data are unavailable. Taken together, the preponderance of evidence indicates that K994N 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		0.862302	Disordered	0.930054	Binding	0.289	0.912	0.750											-3.724	Likely Benign	0.519	Ambiguous	Likely Benign										0.009	Likely Benign	-0.73	Neutral	0.255	Benign	0.113	Benign	4.09	Benign	0.01	Affected			0.4010	0.2376		1	0	0.4	-14.07
c.3001C>G	L1001V 2D AIThe SynGAP1 missense variant L1001V 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, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the available predictions points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.958507	Binding	0.269	0.902	0.375											-3.865	Likely Benign	0.075	Likely Benign	Likely Benign										0.035	Likely Benign	-0.20	Neutral	0.022	Benign	0.008	Benign	2.71	Benign	0.00	Affected			0.1569	0.2714		2	1	0.4	-14.03
c.3007A>G	S1003G 2D AIThe SynGAP1 missense variant S1003G is catalogued in gnomAD (ID 6‑33443559‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for S1003G, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625								6-33443559-A-G	1	6.20e-7	-5.888	Likely Benign	0.542	Ambiguous	Likely Benign										0.088	Likely Benign	-1.72	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.48	Pathogenic	0.00	Affected	3.77	5	0.2730	0.4789		0	1	0.4	-30.03
c.3013A>G	S1005G 2D AIThe SynGAP1 missense change S1005G is catalogued in gnomAD (ID 6‑33443565‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. No Foldetta stability analysis is available for this residue. Overall, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750								6-33443565-A-G			-6.785	Likely Benign	0.537	Ambiguous	Likely Benign										0.095	Likely Benign	-1.98	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.63	Benign	0.00	Affected	3.77	5	0.2328	0.3514		0	1	0.4	-30.03
c.3019A>G	S1007G 2D AIThe SynGAP1 missense variant S1007G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750											-4.051	Likely Benign	0.297	Likely Benign	Likely Benign										0.098	Likely Benign	-1.49	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.73	Benign	0.05	Affected			0.2361	0.4341		1	0	0.4	-30.03
c.304T>G	L102V 2D AIThe SynGAP1 missense variant L102V is listed in ClinVar (ID 1925749.0) with an “Uncertain” status and is present in gnomAD (6‑33432169‑T‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This consensus does not contradict the ClinVar “Uncertain” classification, which remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.795062	Disordered	0.696014	Binding	0.357	0.885	0.625					Uncertain		1	6-33432169-T-G	1	6.20e-7	-4.316	Likely Benign	0.068	Likely Benign	Likely Benign										0.102	Likely Benign	0.32	Neutral	0.880	Possibly Damaging	0.899	Possibly Damaging	4.21	Benign	0.00	Affected	4.32	1	0.1683	0.3671		2	1	0.4	-14.03
c.3064C>G	L1022V 2D AIThe SynGAP1 missense variant L1022V 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 flags the variant as pathogenic, creating a single discordant prediction. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500											-3.957	Likely Benign	0.174	Likely Benign	Likely Benign										0.035	Likely Benign	-1.22	Neutral	0.664	Possibly Damaging	0.260	Benign	2.66	Benign	0.07	Tolerated			0.1702	0.4045		2	1	0.4	-14.03
c.3070C>G	L1024V 2D AIThe SynGAP1 missense variant L1024V is 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 the variant. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-3.758	Likely Benign	0.244	Likely Benign	Likely Benign										0.041	Likely Benign	-1.33	Neutral	0.907	Possibly Damaging	0.642	Possibly Damaging	2.47	Pathogenic	0.08	Tolerated			0.1459	0.3185		2	1	0.4	-14.03
c.3082C>G	L1028V 2D AIThe SynGAP1 missense variant L1028V 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 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of computational evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500											-3.992	Likely Benign	0.217	Likely Benign	Likely Benign										0.042	Likely Benign	-0.68	Neutral	0.737	Possibly Damaging	0.376	Benign	2.74	Benign	0.26	Tolerated			0.1328	0.2715		2	1	0.4	-14.03
c.3094C>G	L1032V 2D AIThe SynGAP1 missense variant L1032V 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 polyPhen‑2 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 not available. Overall, the majority of evidence points to a benign impact for the variant, 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		0.865454	Disordered	0.995318	Binding	0.365	0.735	0.500											-4.123	Likely Benign	0.176	Likely Benign	Likely Benign										0.075	Likely Benign	0.16	Neutral	0.889	Possibly Damaging	0.514	Possibly Damaging	2.78	Benign	0.78	Tolerated			0.1637	0.4353		2	1	0.4	-14.03
c.3157A>G	S1053G 2D AIThe SynGAP1 missense variant S1053G is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly suggests that S1053G is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875											-1.016	Likely Benign	0.050	Likely Benign	Likely Benign										0.220	Likely Benign	-0.57	Neutral	0.001	Benign	0.002	Benign	5.32	Benign	0.59	Tolerated			0.2724	0.5046		1	0	0.4	-30.03
c.3169A>G	S1057G 2D AIThe SynGAP1 missense variant S1057G is reported in gnomAD (ID 6‑33443721‑A‑G) but has no ClinVar entry. All evaluated in‑silico predictors uniformly classify the change as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.988291	Disordered	0.869507	Binding	0.413	0.927	0.875								6-33443721-A-G	1	7.20e-7	-1.005	Likely Benign	0.049	Likely Benign	Likely Benign										0.211	Likely Benign	-0.47	Neutral	0.421	Benign	0.111	Benign	5.76	Benign	0.52	Tolerated	3.77	5	0.2654	0.4846		0	1	0.4	-30.03
c.3202T>G	L1068V 2D AIThe SynGAP1 missense variant L1068V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.947281	Disordered	0.981041	Binding	0.362	0.907	0.875											-5.325	Likely Benign	0.078	Likely Benign	Likely Benign										0.051	Likely Benign	-0.58	Neutral	0.451	Benign	0.110	Benign	2.54	Benign	0.00	Affected			0.1619	0.4404		2	1	0.4	-14.03
c.3214A>C	K1072Q 2D AIThe SynGAP1 missense variant K1072Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-1.631	Likely Benign	0.589	Likely Pathogenic	Likely Benign										0.081	Likely Benign	-0.63	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.95	Benign	0.12	Tolerated			0.4465	0.1804		1	1	0.4	-0.04
c.3214A>G	K1072E 2D AIThe SynGAP1 missense variant K1072E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are returned by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments indicate that AlphaMissense‑Optimized classifies the variant as pathogenic, whereas the SGM‑Consensus (derived from the same set of predictors) labels it as likely benign. No Foldetta stability analysis is available for this residue. Overall, the majority of tools lean toward a benign effect, but the presence of pathogenic calls from several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of evidence, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-3.889	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-0.90	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.96	Benign	0.08	Tolerated			0.3636	0.1874		0	1	0.4	0.94
c.3216G>C	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3216G>T	K1072N 2D AIThe SynGAP1 missense variant K1072N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the balance of evidence leans toward a benign impact, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750											-2.215	Likely Benign	0.953	Likely Pathogenic	Ambiguous										0.078	Likely Benign	-1.18	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	3.92	Benign	0.05	Affected			0.3449	0.2391		1	0	0.4	-14.07
c.3226T>G	L1076V 2D AIThe SynGAP1 missense variant L1076V is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, 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; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while 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		0.922952	Disordered	0.989617	Binding	0.301	0.892	0.750											-3.615	Likely Benign	0.344	Ambiguous	Likely Benign										0.097	Likely Benign	-0.56	Neutral	0.995	Probably Damaging	0.982	Probably Damaging	2.53	Benign	0.11	Tolerated			0.1632	0.3781		2	1	0.4	-14.03
c.322A>C	K108Q 2D AIThe SynGAP1 missense variant K108Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.676	Likely Benign	0.639	Likely Pathogenic	Likely Benign										0.168	Likely Benign	-0.73	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.09	Benign	0.06	Tolerated			0.4843	0.1322		1	1	0.4	-0.04
c.322A>G	K108E 2D AIThe SynGAP1 K108E missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus indicates a likely benign outcome; Foldetta results are unavailable. Overall, the predictions are split evenly between benign and pathogenic, with no clear majority. Consequently, the variant’s impact remains uncertain, and there is no contradiction with ClinVar status, which currently lists no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.679	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-1.24	Neutral	0.993	Probably Damaging	0.956	Probably Damaging	4.12	Benign	0.04	Affected			0.4145	0.1166		0	1	0.4	0.94
c.3235A>G	S1079G 2D AIThe SynGAP1 missense variant S1079G is reported in gnomAD (variant ID 6‑33443787‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750								6-33443787-A-G	6	3.76e-6	-3.552	Likely Benign	0.177	Likely Benign	Likely Benign										0.065	Likely Benign	-1.50	Neutral	0.036	Benign	0.018	Benign	3.87	Benign	0.00	Affected	3.77	5	0.2151	0.4623		0	1	0.4	-30.03
c.3247A>C	K1083Q 2D AIThe SynGAP1 missense variant K1083Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv and HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign effect. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports 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 both general and high‑accuracy tools points to a benign impact for K1083Q, 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	0.978906	Binding	0.302	0.893	1.000											-2.214	Likely Benign	0.390	Ambiguous	Likely Benign										0.099	Likely Benign	-0.50	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.06	Benign	0.37	Tolerated			0.4821	0.1647		1	1	0.4	-0.04
c.3247A>G	K1083E 2D AIThe SynGAP1 missense variant K1083E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-3.538	Likely Benign	0.864	Likely Pathogenic	Ambiguous										0.133	Likely Benign	-0.78	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	4.09	Benign	0.27	Tolerated			0.4135	0.1717		0	1	0.4	0.94
c.3249A>C	K1083N 2D AIThe SynGAP1 missense variant K1083N is not reported 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		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-4.088	Likely Benign	0.873	Likely Pathogenic	Ambiguous										0.053	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.04	Benign	0.21	Tolerated			0.3939	0.2234		1	0	0.4	-14.07
c.3249A>T	K1083N 2D AIThe SynGAP1 missense variant K1083N is not reported 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		0.837511	Disordered	0.978906	Binding	0.302	0.893	1.000											-4.088	Likely Benign	0.873	Likely Pathogenic	Ambiguous										0.053	Likely Benign	-0.83	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.04	Benign	0.21	Tolerated			0.3939	0.2234		1	0	0.4	-14.07
c.324G>C	K108N 2D AISynGAP1 missense variant K108N is reported in gnomAD (6‑33432189‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign); pathogenic calls from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenic, whereas the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign; Foldetta results are unavailable. Consequently, the evidence is evenly split, with no single prediction dominating. The variant is therefore not clearly benign or pathogenic based on current computational data, and this lack of consensus does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875								6-33432189-G-C	1	6.20e-7	-3.015	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.068	Likely Benign	-1.35	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.07	Benign	0.03	Affected	3.61	5	0.3904	0.1820		0	1	0.4	-14.07
c.324G>T	K108N 2D AIThe SynGAP1 missense variant K108N is not reported in ClinVar and has no gnomAD entry. Consensus predictions from multiple in‑silico tools are split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which labels the variant as Likely Benign. Pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized, the latter two high‑accuracy predictors both flagging the variant as Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not return a result for this variant, so its stability impact is unavailable. Overall, the majority of high‑confidence tools (AlphaMissense‑Optimized and the SGM‑Consensus) disagree, with AlphaMissense‑Optimized indicating pathogenicity while the consensus suggests benign. Because ClinVar contains no classification, there is no contradiction; the variant is most likely pathogenic based on the most reliable predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875											-3.015	Likely Benign	0.964	Likely Pathogenic	Likely Pathogenic										0.068	Likely Benign	-1.35	Neutral	0.998	Probably Damaging	0.981	Probably Damaging	4.07	Benign	0.03	Affected	3.61	5	0.3904	0.1820		0	1	0.4	-14.07
c.325A>G	S109G 2D AIThe SynGAP1 missense variant S109G is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750											-3.918	Likely Benign	0.549	Ambiguous	Likely Benign										0.132	Likely Benign	-1.95	Neutral	0.378	Benign	0.067	Benign	3.51	Benign	0.00	Affected			0.2686	0.3779		1	0	0.4	-30.03
c.3262A>G	S1088G 2D AIThe SynGAP1 missense variant S1088G is listed in ClinVar (ID 2742833.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as Likely Benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000					Uncertain		1				-5.034	Likely Benign	0.285	Likely Benign	Likely Benign										0.163	Likely Benign	-1.83	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	2.63	Benign	0.03	Affected	3.77	5	0.2541	0.5170		0	1	0.4	-30.03
c.3271C>G	L1091V 2D AIThe SynGAP1 missense variant L1091V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports Likely Benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the lack of ClinVar evidence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000											-4.587	Likely Benign	0.328	Likely Benign	Likely Benign										0.048	Likely Benign	-0.62	Neutral	0.779	Possibly Damaging	0.211	Benign	2.57	Benign	0.08	Tolerated			0.1560	0.3561		2	1	0.4	-14.03
c.3274T>G	L1092V 2D AIThe SynGAP1 missense variant L1092V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. 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		0.924947	Disordered	0.985431	Binding	0.385	0.890	1.000											-4.906	Likely Benign	0.451	Ambiguous	Likely Benign										0.034	Likely Benign	-0.36	Neutral	0.051	Benign	0.037	Benign	2.79	Benign	0.37	Tolerated			0.1658	0.3912		2	1	0.4	-14.03
c.3292A>G	S1098G 2D AIThe SynGAP1 missense variant S1098G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the collective predictions strongly support a benign impact, and this conclusion is consistent with the lack of a ClinVar pathogenic classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.973030	Binding	0.337	0.855	1.000											-3.494	Likely Benign	0.072	Likely Benign	Likely Benign										0.066	Likely Benign	-0.39	Neutral	0.000	Benign	0.001	Benign	2.72	Benign	0.57	Tolerated			0.2634	0.5206		1	0	0.4	-30.03
c.3322A>G	S1108G 2D AIThe SynGAP1 missense variant S1108G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence (six benign vs three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.949221	Binding	0.324	0.886	0.875											-6.496	Likely Benign	0.126	Likely Benign	Likely Benign										0.084	Likely Benign	-2.59	Deleterious	0.568	Possibly Damaging	0.239	Benign	2.46	Pathogenic	0.16	Tolerated			0.2268	0.3975		1	0	0.4	-30.03
c.3325C>G	L1109V 2D AIThe SynGAP1 missense variant L1109V is catalogued in gnomAD (ID 6‑33443877‑C‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign verdict. Foldetta results are not available for this variant. Consequently, the variant is most likely benign, 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.	Likely Benign		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875								6-33443877-C-G			-5.490	Likely Benign	0.062	Likely Benign	Likely Benign										0.091	Likely Benign	-0.52	Neutral	0.001	Benign	0.005	Benign	2.72	Benign	0.19	Tolerated	4.32	2	0.1676	0.4353		1	2	0.4	-14.03
c.3328A>G	S1110G 2D AIThe SynGAP1 missense variant S1110G is listed in ClinVar (ID 1722210.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.912647	Disordered	0.934156	Binding	0.346	0.892	0.875					Likely Benign		1				-4.674	Likely Benign	0.079	Likely Benign	Likely Benign										0.035	Likely Benign	-2.26	Neutral	0.036	Benign	0.026	Benign	2.19	Pathogenic	0.08	Tolerated	4.32	2	0.2559	0.4806		1	0	0.4	-30.03
c.3331A>C	K1111Q 2D AIThe SynGAP1 missense variant K1111Q 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 classify the change as benign, while only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely benign. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates likely benign; Foldetta results are not available. Overall, the consensus of available predictions indicates that K1111Q 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		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875											-3.687	Likely Benign	0.261	Likely Benign	Likely Benign										0.036	Likely Benign	-0.80	Neutral	0.666	Possibly Damaging	0.267	Benign	2.66	Benign	0.31	Tolerated			0.4577	0.1714		1	1	0.4	-0.04
c.3331A>G	K1111E 2D AIThe SynGAP1 missense variant K1111E is not reported in ClinVar and has no entry in gnomAD. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all score it as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy tools further support a benign interpretation: AlphaMissense‑Optimized returns a benign prediction, while the SGM‑Consensus (majority vote) remains benign; a Foldetta stability assessment is unavailable. Taken together, 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		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875											-3.666	Likely Benign	0.565	Likely Pathogenic	Likely Benign										0.089	Likely Benign	-0.86	Neutral	0.451	Benign	0.193	Benign	2.69	Benign	0.23	Tolerated			0.3846	0.1833		0	1	0.4	0.94
c.3333G>C	K1111N 2D AIThe SynGAP1 missense variant K1111N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. 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		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875											-4.503	Likely Benign	0.833	Likely Pathogenic	Ambiguous										0.048	Likely Benign	-0.77	Neutral	0.666	Possibly Damaging	0.211	Benign	2.64	Benign	0.15	Tolerated			0.3667	0.2350		1	0	0.4	-14.07
c.3333G>T	K1111N 2D AIThe SynGAP1 missense variant K1111N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and AlphaMissense‑Optimized is uncertain. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875											-4.503	Likely Benign	0.833	Likely Pathogenic	Ambiguous										0.048	Likely Benign	-0.77	Neutral	0.666	Possibly Damaging	0.211	Benign	2.64	Benign	0.15	Tolerated			0.3667	0.2350		1	0	0.4	-14.07
c.3340A>G	S1114G 2D AIThe SynGAP1 missense variant S1114G is reported in gnomAD (ID 6‑33443892‑A‑G) but has no ClinVar entry. All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.895196	Binding	0.295	0.908	0.875								6-33443892-A-G			-3.894	Likely Benign	0.064	Likely Benign	Likely Benign										0.080	Likely Benign	-1.33	Neutral	0.000	Benign	0.000	Benign	2.75	Benign	0.08	Tolerated	4.32	2	0.2414	0.4914		0	1	0.4	-30.03
c.3352A>G	S1118G 2D AIThe SynGAP1 missense variant S1118G is reported in gnomAD (ID 6‑33443904‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the preponderance of evidence indicates that S1118G is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750								6-33443904-A-G	1	6.98e-7	-1.615	Likely Benign	0.057	Likely Benign	Likely Benign										0.146	Likely Benign	-0.61	Neutral	0.790	Possibly Damaging	0.433	Benign	5.82	Benign	0.08	Tolerated	4.32	2	0.2737	0.4657		0	1	0.4	-30.03
c.3361A>G	S1121G 2D AIThe SynGAP1 missense variant S1121G is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443913‑A‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, which does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875					Uncertain		1	6-33443913-A-G	1	7.00e-7	-1.220	Likely Benign	0.054	Likely Benign	Likely Benign										0.067	Likely Benign	-0.53	Neutral	0.003	Benign	0.004	Benign	6.63	Benign	0.00	Affected	3.77	5	0.2724	0.4657		0	1	0.4	-30.03
c.3385C>G	L1129V 2D AIThe SynGAP1 missense variant L1129V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.876543	Binding	0.339	0.909	0.875											-3.595	Likely Benign	0.093	Likely Benign	Likely Benign										0.262	Likely Benign	-0.87	Neutral	0.393	Benign	0.187	Benign	5.46	Benign	0.00	Affected			0.1814	0.3804		2	1	0.4	-14.03
c.3388A>C	K1130Q 2D AIThe SynGAP1 missense variant K1130Q is reported in gnomAD (ID 6‑33443940‑A‑C) but has no ClinVar entry. Functional 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 and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact, 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		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750								6-33443940-A-C			-3.548	Likely Benign	0.529	Ambiguous	Likely Benign										0.337	Likely Benign	-1.25	Neutral	0.818	Possibly Damaging	0.355	Benign	5.44	Benign	0.00	Affected	4.32	4	0.4964	0.1756		1	1	0.4	-0.04
c.3388A>G	K1130E 2D AIThe SynGAP1 missense variant K1130E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Benign classification, while AlphaMissense‑Optimized remains Uncertain. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of tools and the SGM consensus support a benign impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.998	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.422	Likely Benign	-1.23	Neutral	0.649	Possibly Damaging	0.266	Benign	5.45	Benign	0.00	Affected			0.4251	0.1876		0	1	0.4	0.94
c.3390G>C	K1130N 2D AIThe SynGAP1 missense variant K1130N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which classifies it as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Thus, based on current computational predictions, the K1130N variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.822	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-1.02	Neutral	0.818	Possibly Damaging	0.287	Benign	5.43	Benign	0.00	Affected			0.4119	0.2393		1	0	0.4	-14.07
c.3390G>T	K1130N 2D AIThe SynGAP1 missense variant K1130N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which classifies it as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available prediction for this variant. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict ClinVar, as no ClinVar entry exists. Thus, based on current computational predictions, the K1130N variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.863782	Binding	0.350	0.904	0.750											-4.822	Likely Benign	0.946	Likely Pathogenic	Ambiguous										0.336	Likely Benign	-1.02	Neutral	0.818	Possibly Damaging	0.287	Benign	5.43	Benign	0.00	Affected			0.4119	0.2393		1	0	0.4	-14.07
c.3403A>C	K1135Q 2D AIThe SynGAP1 missense variant K1135Q has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, 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		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875											-4.622	Likely Benign	0.566	Likely Pathogenic	Likely Benign										0.171	Likely Benign	-0.66	Neutral	0.099	Benign	0.150	Benign	5.43	Benign	0.07	Tolerated			0.5016	0.1356	Weaken	1	1	0.4	-0.04
c.3403A>G	K1135E 2D AIThe SynGAP1 missense variant K1135E is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443955‑A‑G). 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta) results are unavailable. Overall, the preponderance of evidence points to a benign impact for K1135E, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875								6-33443955-A-G			-6.499	Likely Benign	0.924	Likely Pathogenic	Ambiguous										0.239	Likely Benign	-0.76	Neutral	0.224	Benign	0.237	Benign	5.45	Benign	0.12	Tolerated	4.32	2	0.4330	0.1476		1	0	0.4	0.94
c.3405G>C	K1135N 2D AIThe SynGAP1 missense variant K1135N is listed in ClinVar (ID 633521.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. In contrast, AlphaMissense‑Default and AlphaMissense‑Optimized both predict a pathogenic outcome. High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Benign. No Foldetta (FoldX‑MD/Rosetta stability) result is available for this variant. Overall, the majority of predictions support a benign classification, which does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875					Uncertain		1				-5.715	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-0.97	Neutral	0.411	Benign	0.321	Benign	5.43	Benign	0.07	Tolerated	4.32	2	0.4152	0.1793		1	0	0.4	-14.07
c.3405G>T	K1135N 2D AIThe SynGAP1 missense variant K1135N is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443957‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the majority of predictions (seven benign vs. two pathogenic) support a benign interpretation. This consensus does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.790969	Binding	0.303	0.889	0.875								6-33443957-G-T			-5.715	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic										0.166	Likely Benign	-0.97	Neutral	0.411	Benign	0.321	Benign	5.43	Benign	0.07	Tolerated	4.32	2	0.4152	0.1793		1	0	0.4	-14.07
c.340A>C	K114Q 2D AIThe SynGAP1 missense variant K114Q 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, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and there is no ClinVar annotation to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.221	Likely Benign	0.467	Ambiguous	Likely Benign										0.058	Likely Benign	-1.33	Neutral	0.608	Possibly Damaging	0.108	Benign	3.98	Benign	0.00	Affected			0.5476	0.1530	Weaken	1	1	0.4	-0.04
c.340A>G	K114E 2D AISynGAP1 missense variant K114E 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, while AlphaMissense‑Optimized is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta (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, as none exists for K114E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-2.648	Likely Benign	0.885	Likely Pathogenic	Ambiguous										0.093	Likely Benign	-1.27	Neutral	0.005	Benign	0.003	Benign	4.01	Benign	0.00	Affected			0.4815	0.1340		0	1	0.4	0.94
c.342G>C	K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.342G>T	K114N 2D AIThe SynGAP1 missense variant K114N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.649749	Binding	0.381	0.879	0.750											-3.851	Likely Benign	0.937	Likely Pathogenic	Ambiguous										0.045	Likely Benign	-1.41	Neutral	0.608	Possibly Damaging	0.190	Benign	3.95	Benign	0.00	Affected			0.4590	0.1877		1	0	0.4	-14.07
c.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.3490C>G	L1164V 2D AIThe SynGAP1 missense variant L1164V has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic 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 no Foldetta stability data are available. Overall, the balance of evidence leans toward 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.	Likely Benign		0.517562	Disordered	0.853935	Binding	0.325	0.815	0.375											-4.911	Likely Benign	0.797	Likely Pathogenic	Ambiguous										0.330	Likely Benign	-0.88	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.54	Benign	0.14	Tolerated			0.1456	0.2617		2	1	0.4	-14.03
c.349A>G	S117G 2D AIThe SynGAP1 missense variant S117G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625											-3.280	Likely Benign	0.174	Likely Benign	Likely Benign										0.122	Likely Benign	-1.59	Neutral	0.390	Benign	0.066	Benign	3.73	Benign	0.01	Affected			0.2113	0.4627		1	0	0.4	-30.03
c.34A>G	S12G 2D AIThe SynGAP1 missense variant S12G is reported in gnomAD (ID 6‑33420298‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for S12G, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.490599	Uncertain	0.355	0.916	0.500								6-33420298-A-G			-4.229	Likely Benign	0.093	Likely Benign	Likely Benign										0.079	Likely Benign	0.22	Neutral	0.103	Benign	0.015	Benign	4.11	Benign	0.00	Affected	4.32	1	0.2876	0.5080		0	1	0.4	-30.03
c.3508A>G	S1170G 2D AIThe SynGAP1 missense variant S1170G is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on benign impact include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500					Uncertain		1				-4.288	Likely Benign	0.221	Likely Benign	Likely Benign										0.349	Likely Benign	-0.81	Neutral	0.241	Benign	0.229	Benign	5.31	Benign	0.54	Tolerated	4.32	4	0.2705	0.4558		1	0	0.4	-30.03
c.3535A>C	K1179Q 2D AIThe SynGAP1 missense variant K1179Q is reported in gnomAD (variant ID 6‑33444570‑A‑C) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy tools, point to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250								6-33444570-A-C	1	6.20e-7	-4.237	Likely Benign	0.679	Likely Pathogenic	Likely Benign										0.078	Likely Benign	-1.20	Neutral	0.430	Benign	0.211	Benign	2.67	Benign	0.00	Affected	4.32	2	0.4037	0.0807		1	1	0.4	-0.04
c.3535A>G	K1179E 2D AIThe SynGAP1 missense variant K1179E is reported in gnomAD (ID 6‑33444570‑A‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic impact are polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Benign, and Foldetta results are unavailable. Overall, the majority of individual predictors (five versus four) lean toward pathogenicity, and the high‑accuracy AlphaMissense‑Optimized result supports this. No ClinVar status is available to contradict these findings. Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250								6-33444570-A-G	1	6.20e-7	-4.040	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.143	Likely Benign	-1.02	Neutral	0.800	Possibly Damaging	0.525	Possibly Damaging	2.96	Benign	0.00	Affected	4.32	2	0.3476	0.0876		1	0	0.4	0.94
c.3537G>C	K1179N 2D AIThe SynGAP1 missense variant K1179N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Among general in‑silico predictors, benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of high‑confidence predictions lean toward pathogenicity, and there is no ClinVar annotation to contradict this assessment. Thus, the variant is most likely pathogenic based on the current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250											-4.764	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.113	Likely Benign	-1.57	Neutral	0.975	Probably Damaging	0.766	Possibly Damaging	2.68	Benign	0.00	Affected			0.3490	0.0901		1	0	0.4	-14.07
c.3537G>T	K1179N 2D AIThe SynGAP1 K1179N missense variant is not reported in ClinVar and has no entries in gnomAD. General in silico predictors cluster into two groups: benign predictions from REVEL, PROVEAN, ESM1b, and FATHMM; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy tools provide a mixed signal: AlphaMissense‑Optimized classifies the change as pathogenic, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect; Foldetta results are unavailable. Overall, the evidence is split, with no single consensus. Thus, the variant is currently inconclusive—neither clearly benign nor pathogenic—and 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	0.637480	Disordered	0.558455	Binding	0.575	0.678	0.250											-4.764	Likely Benign	0.983	Likely Pathogenic	Likely Pathogenic										0.113	Likely Benign	-1.57	Neutral	0.975	Probably Damaging	0.766	Possibly Damaging	2.68	Benign	0.00	Affected			0.3490	0.0901		1	0	0.4	-14.07
c.3538C>G	L1180V 2D AIThe SynGAP1 missense variant L1180V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Grouping by consensus, the majority of tools (five) predict benign, while four predict pathogenic. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. AlphaMissense‑Optimized independently predicts benign. No Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-4.664	Likely Benign	0.741	Likely Pathogenic	Likely Benign										0.086	Likely Benign	-1.00	Neutral	0.856	Possibly Damaging	0.474	Possibly Damaging	2.71	Benign	0.00	Affected			0.1386	0.1991		2	1	0.4	-14.03
c.3541A>C	K1181Q 2D AIThe SynGAP1 K1181Q missense variant is reported in gnomAD (variant ID 6‑33444576‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions points to a benign effect, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375								6-33444576-A-C			-3.724	Likely Benign	0.779	Likely Pathogenic	Likely Benign										0.173	Likely Benign	-1.48	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.66	Benign	0.07	Tolerated	4.32	3	0.3415	0.1102		1	1	0.4	-0.04
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.3543G>C	K1181N 2D AISynGAP1 missense variant K1181N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, whereas the SGM‑Consensus remains Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a pathogenic effect, and this conclusion does not conflict with ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-4.872	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.111	Likely Benign	-1.94	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.65	Benign	0.02	Affected			0.2812	0.1302		1	0	0.4	-14.07
c.3543G>T	K1181N 2D AIThe SynGAP1 missense variant K1181N is not reported in ClinVar and has no gnomAD entry. Prediction tools that classify it as benign include REVEL, PROVEAN, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus again indicates Likely Benign; Foldetta results are unavailable. Overall, the predictions are mixed, with a slight edge toward pathogenicity from individual tools but a consensus leaning benign. Therefore, the variant is most likely benign based on the collective evidence, and this assessment does not contradict ClinVar status, which currently has no classification for K1181N. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.539278	Binding	0.625	0.660	0.375											-4.872	Likely Benign	0.992	Likely Pathogenic	Likely Pathogenic										0.111	Likely Benign	-1.94	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	2.65	Benign	0.02	Affected			0.2812	0.1302		1	0	0.4	-14.07
c.3553A>C	K1185Q 2D AIThe SynGAP1 K1185Q missense change 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, 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, reports a “Likely Benign” classification. AlphaMissense‑Optimized yields an uncertain result, and no Foldetta stability assessment is available. Considering the high‑accuracy evidence, the consensus remains “Likely Benign” and the AlphaMissense‑Optimized prediction is inconclusive. 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	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.256	Likely Benign	0.865	Likely Pathogenic	Ambiguous										0.125	Likely Benign	-0.92	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.74	Benign	0.37	Tolerated			0.4371	0.0945		1	1	0.4	-0.04
c.3553A>G	K1185E 2D AISynGAP1 K1185E is not reported in ClinVar and has no gnomAD allele. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further highlight this divergence: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (a majority‑vote method) indicates benign; Foldetta results are unavailable. Overall, the balance of evidence, including the consensus from multiple predictors, points to a benign effect. Thus, the variant is most likely benign, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.465	Likely Benign	0.980	Likely Pathogenic	Likely Pathogenic										0.148	Likely Benign	-1.34	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.89	Benign	0.19	Tolerated			0.3715	0.0720		0	1	0.4	0.94
c.3555A>C	K1185N 2D AIThe SynGAP1 missense variant K1185N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default both predict a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as likely benign, whereas AlphaMissense‑Optimized predicts pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions lean toward a benign interpretation, and there is no ClinVar entry 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.	Likely Benign	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.345	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.04	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.68	Benign	0.12	Tolerated			0.3653	0.1145		1	0	0.4	-14.07
c.3555A>T	K1185N 2D AIThe SynGAP1 missense variant K1185N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a mixed signal: benign calls come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further split the verdict: AlphaMissense‑Optimized predicts Pathogenic, whereas the SGM‑Consensus (majority vote) indicates Likely Benign; Foldetta results are unavailable. Overall, the balance of evidence slightly favors a benign interpretation, and there is no conflict with ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.510264	Binding	0.642	0.638	0.625											-4.345	Likely Benign	0.993	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.04	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.68	Benign	0.12	Tolerated			0.3653	0.1145		1	0	0.4	-14.07
c.3568A>G	S1190G 2D AIThe SynGAP1 missense change S1190G is catalogued in gnomAD (ID 6‑33444603‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign (REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) and pathogenic (AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar). High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also favors benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Taken together, the preponderance of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.455760	Uncertain	0.742	0.624	0.625								6-33444603-A-G	1	6.20e-7	-3.078	Likely Benign	0.647	Likely Pathogenic	Likely Benign										0.374	Likely Benign	-1.13	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	5.28	Benign	0.42	Tolerated	3.82	4	0.2312	0.3549		0	1	0.4	-30.03
c.3574C>G	L1192V 2D AIThe SynGAP1 missense variant L1192V is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized score is benign, and the SGM‑Consensus also indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.441757	Uncertain	0.762	0.609	0.625					Uncertain		1				-4.132	Likely Benign	0.471	Ambiguous	Likely Benign										0.041	Likely Benign	-0.89	Neutral	0.779	Possibly Damaging	0.527	Possibly Damaging	2.69	Benign	0.16	Tolerated			0.1441	0.2289		2	1	0.4	-14.03
c.3586A>C	K1196Q 2D AIThe SynGAP1 missense variant K1196Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the preponderance of benign predictions and the lack of pathogenic evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-5.222	Likely Benign	0.346	Ambiguous	Likely Benign										0.342	Likely Benign	-0.65	Neutral	0.989	Probably Damaging	0.819	Possibly Damaging	5.38	Benign	0.07	Tolerated			0.3814	0.0945		1	1	0.4	-0.04
c.3586A>G	K1196E 2D AIThe SynGAP1 missense variant K1196E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools are divided: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates 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. 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 Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.382	Likely Benign	0.734	Likely Pathogenic	Likely Benign										0.358	Likely Benign	-0.02	Neutral	0.961	Probably Damaging	0.764	Possibly Damaging	5.38	Benign	0.42	Tolerated			0.3272	0.0720		0	1	0.4	0.94
c.3588G>C	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized predicting pathogenicity, whereas the SGM‑Consensus indicates benignity; a Foldetta stability analysis is unavailable. Overall, the majority of tools (five pathogenic vs. four benign) suggest the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.3588G>T	K1196N 2D AIThe SynGAP1 missense variant K1196N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments further divide the evidence: AlphaMissense‑Optimized predicts a pathogenic effect, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome; Foldetta stability analysis is unavailable. With no ClinVar classification to resolve the conflict, the overall computational signal is inconclusive, but the presence of a pathogenic prediction from a high‑accuracy model and the absence of a benign consensus suggest the variant is more likely pathogenic. This assessment does not contradict any ClinVar status, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.435699	Uncertain	0.851	0.595	0.250											-6.421	Likely Benign	0.959	Likely Pathogenic	Likely Pathogenic										0.305	Likely Benign	-1.73	Neutral	0.994	Probably Damaging	0.819	Possibly Damaging	5.37	Benign	0.04	Affected			0.3251	0.1145		1	0	0.4	-14.07
c.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.3616A>C	K1206Q 2D AIThe SynGAP1 K1206Q 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, SIFT, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, 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 inconclusive, and Foldetta data are unavailable. Consequently, the evidence is evenly split between benign and pathogenic interpretations. The variant therefore falls into a category of uncertain significance, with no conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-8.654	Likely Pathogenic	0.817	Likely Pathogenic	Ambiguous										0.130	Likely Benign	-0.92	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.49	Tolerated			0.3829	0.1219		1	1	0.4	-0.04
c.3616A>G	K1206E 2D AIThe SynGAP1 missense variant K1206E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas the majority of tools predict a pathogenic impact: polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as no ClinVar classification exists for K1206E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.025	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-1.87	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	2.44	Pathogenic	0.02	Affected			0.3247	0.1039		0	1	0.4	0.94
c.3618A>C	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N 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	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3618A>T	K1206N 2D AIThe SynGAP1 missense variant K1206N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the preponderance of pathogenic predictions, K1206N 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	0.585406	Disordered	0.555819	Binding	0.893	0.569	0.375											-11.172	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.41	Pathogenic	0.01	Affected			0.3169	0.1464		1	0	0.4	-14.07
c.3625C>G	L1209V 2D AIThe SynGAP1 L1209V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Taken together, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375											-9.962	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous										0.152	Likely Benign	-2.39	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			0.1383	0.2289		2	1	0.4	-14.03
c.3643A>C	K1215Q 2D AIThe SynGAP1 missense variant K1215Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are REVEL and PROVEAN, whereas the remaining tools—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—consistently predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic impact for K1215Q, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-9.763	Likely Pathogenic	0.948	Likely Pathogenic	Ambiguous										0.099	Likely Benign	-2.23	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.02	Affected			0.4002	0.0856		1	1	0.4	-0.04
c.3643A>G	K1215E 2D AISynGAP1 missense variant K1215E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction from REVEL versus pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta stability analysis is unavailable. Overall, the consensus of available tools indicates that K1215E 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	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-14.365	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.156	Likely Benign	-2.65	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.40	Pathogenic	0.01	Affected			0.3403	0.0676		0	1	0.4	0.94
c.3645G>C	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N 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	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3645G>T	K1215N 2D AIThe SynGAP1 missense variant K1215N is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K1215N 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	0.497853	Structured	0.503613	Binding	0.888	0.568	0.375											-12.569	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-3.23	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.38	Pathogenic	0.01	Affected			0.3380	0.0901		1	0	0.4	-14.07
c.3646C>G	L1216V 2D AIThe SynGAP1 missense variant L1216V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two agreement groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessment further shows that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250											-7.842	In-Between	0.861	Likely Pathogenic	Ambiguous										0.126	Likely Benign	-2.26	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.20	Pathogenic	0.00	Affected			0.1294	0.1883		2	1	0.4	-14.03
c.3667C>G	L1223V 2D AIThe SynGAP1 missense variant L1223V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic, reflecting a majority of pathogenic calls. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote) 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, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375											-8.492	Likely Pathogenic	0.678	Likely Pathogenic	Likely Benign										0.178	Likely Benign	-2.18	Neutral	0.981	Probably Damaging	0.832	Possibly Damaging	1.54	Pathogenic	0.04	Affected			0.1381	0.2988		2	1	0.4	-14.03
c.3670C>G	L1224V 2D AIThe SynGAP1 missense variant L1224V is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM 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 likely benign. No Foldetta (FoldX‑MD/Rosetta) stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods indicates that the variant is most likely benign, and this conclusion does not contradict the current ClinVar status of “Uncertain.” Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.525368	Disordered	0.441554	Uncertain	0.871	0.543	0.500					Uncertain		1				-5.796	Likely Benign	0.080	Likely Benign	Likely Benign										0.093	Likely Benign	-1.41	Neutral	0.248	Benign	0.112	Benign	2.42	Pathogenic	0.18	Tolerated			0.1397	0.2289		2	1	0.4	-14.03
c.3691A>G	S1231G 2D AIThe SynGAP1 missense variant S1231G is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. The high‑accuracy consensus, SGM‑Consensus, also reports the variant as Likely Benign, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. AlphaMissense‑Optimized independently predicts a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.490133	Structured	0.519419	Binding	0.876	0.544	0.250											-5.384	Likely Benign	0.077	Likely Benign	Likely Benign										0.119	Likely Benign	-1.78	Neutral	0.002	Benign	0.005	Benign	2.66	Benign	0.23	Tolerated			0.2247	0.3614		1	0	0.4	-30.03
c.3694A>C	K1232Q 2D AIThe SynGAP1 missense variant K1232Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of individual predictors (five pathogenic vs four benign) lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-6.905	Likely Benign	0.247	Likely Benign	Likely Benign										0.102	Likely Benign	-2.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.14	Pathogenic	0.00	Affected			0.3457	0.1419		1	1	0.4	-0.04
c.3694A>G	K1232E 2D AIThe SynGAP1 missense variant K1232E 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 tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the 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	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-10.690	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign										0.165	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.13	Pathogenic	0.00	Affected			0.2965	0.1039		0	1	0.4	0.94
c.3696A>C	K1232N 2D AIThe SynGAP1 missense variant K1232N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict it to be pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized returns an uncertain result, and Foldetta data are not available. Based on the overall evidence, the variant is most likely pathogenic, which is consistent with the lack of ClinVar annotation and gnomAD absence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3696A>T	K1232N 2D AIThe SynGAP1 missense variant K1232N 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—consistently predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.505461	Disordered	0.542907	Binding	0.894	0.535	0.125											-8.657	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous										0.167	Likely Benign	-3.72	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.2913	0.1464		1	0	0.4	-14.07
c.3700C>G	L1234V 2D AIThe SynGAP1 missense variant L1234V is not 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 AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. 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, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result. Overall, the balance of evidence leans toward a benign 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.		Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125											-7.863	In-Between	0.402	Ambiguous	Likely Benign										0.090	Likely Benign	-1.80	Neutral	0.898	Possibly Damaging	0.602	Possibly Damaging	1.54	Pathogenic	0.50	Tolerated			0.1314	0.2918		2	1	0.4	-14.03
c.3721C>G	L1241V 2D AIThe SynGAP1 missense variant L1241V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL and PROVEAN, whereas a majority of tools predict a pathogenic impact: polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. AlphaMissense‑Optimized yields an uncertain result, and Foldetta (the combined FoldX‑MD and Rosetta stability assessment) is not available for this variant. Overall, the preponderance of evidence from high‑accuracy predictors points to a pathogenic 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 Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375											-8.771	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous										0.153	Likely Benign	-2.33	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.70	Pathogenic	0.00	Affected			0.1596	0.1883		2	1	0.4	-14.03
c.3730A>G	S1244G 2D AIThe SynGAP1 missense variant S1244G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy evidence therefore comes only from AlphaMissense‑Optimized, which predicts benign, while the other high‑accuracy tools are unavailable. Overall, the balance of evidence (five benign vs four pathogenic predictions, with the most reliable tool indicating benign) suggests that the variant is most likely benign. This conclusion does not contradict ClinVar status, as the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.648219	Disordered	0.411055	Uncertain	0.833	0.549	0.500											-8.304	Likely Pathogenic	0.221	Likely Benign	Likely Benign										0.130	Likely Benign	-1.77	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.12	Pathogenic	0.65	Tolerated			0.2267	0.3678		1	0	0.4	-30.03
c.3736A>C	K1246Q 2D AIThe SynGAP1 missense change K1246Q 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 variant as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as “Likely Benign.” In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that K1246Q is most likely benign, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625											-0.718	Likely Benign	0.107	Likely Benign	Likely Benign										0.071	Likely Benign	-0.43	Neutral	0.961	Probably Damaging	0.721	Possibly Damaging	2.66	Benign	0.06	Tolerated			0.3708	0.0740		1	1	0.4	-0.04
c.3736A>G	K1246E 2D AIThe SynGAP1 missense variant K1246E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the lack of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625											-2.052	Likely Benign	0.305	Likely Benign	Likely Benign										0.127	Likely Benign	0.80	Neutral	0.910	Possibly Damaging	0.630	Possibly Damaging	2.89	Benign	1.00	Tolerated			0.3328	0.0514		0	1	0.4	0.94
c.3738G>C	K1246N 2D AIThe SynGAP1 missense variant K1246N 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 results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence from multiple independent predictors points to a benign effect for K1246N, 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	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625											-2.506	Likely Benign	0.518	Ambiguous	Likely Benign										0.125	Likely Benign	-1.39	Neutral	0.980	Probably Damaging	0.721	Possibly Damaging	2.66	Benign	0.02	Affected			0.3316	0.0940		1	0	0.4	-14.07
c.3738G>T	K1246N 2D AIThe SynGAP1 missense variant K1246N 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 results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence from multiple independent predictors points to a benign effect for K1246N, 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	0.750527	Disordered	0.375382	Uncertain	0.887	0.564	0.625											-2.506	Likely Benign	0.518	Ambiguous	Likely Benign										0.122	Likely Benign	-1.39	Neutral	0.980	Probably Damaging	0.721	Possibly Damaging	2.66	Benign	0.02	Affected			0.3316	0.0940		1	0	0.4	-14.07
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.3763A>C	K1255Q 2D AIThe SynGAP1 missense variant K1255Q is 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. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also reports a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for K1255Q, 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	0.637480	Disordered	0.417615	Uncertain	0.880	0.563	0.625											-12.680	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic										0.282	Likely Benign	-3.19	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.87	Pathogenic	0.00	Affected			0.3625	0.1102		1	1	0.4	-0.04
c.3763A>G	K1255E 2D AIThe SynGAP1 missense variant K1255E is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are not available. 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 reported). 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											-15.072	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.308	Likely Benign	-3.12	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.88	Pathogenic	0.00	Affected			0.3094	0.0877		0	1	0.4	0.94
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.3778A>C	K1260Q 2D AIThe SynGAP1 missense variant K1260Q is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33446770‑A‑C). Functional prediction tools cluster into two groups: benign predictions come from REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. ESM1b is uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a pathogenic verdict, and Foldetta results are unavailable. Overall, the majority of evidence points to pathogenicity, and this conclusion 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	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250								6-33446770-A-C			-7.830	In-Between	0.325	Likely Benign	Likely Benign										0.367	Likely Benign	-3.06	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.36	Pathogenic	0.00	Affected	3.77	5	0.3597	0.1102		1	1	0.4	-0.04
c.3778A>G	K1260E 2D AIThe SynGAP1 missense variant K1260E is 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 tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—predict a pathogenic impact, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions point to a pathogenic effect, 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	Coiled-coil	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-10.913	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous										0.462	Likely Benign	-3.06	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.3129	0.0877		0	1	0.4	0.94
c.3780G>C	K1260N 2D AIThe SynGAP1 missense variant K1260N is 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. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, 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	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3780G>T	K1260N 2D AIThe SynGAP1 missense variant K1260N is 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. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the variant as pathogenic or likely pathogenic. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Based on the consensus of high‑accuracy predictors, 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	0.509769	Disordered	0.625808	Binding	0.890	0.575	0.250											-9.053	Likely Pathogenic	0.915	Likely Pathogenic	Ambiguous										0.157	Likely Benign	-3.39	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.42	Pathogenic	0.00	Affected			0.3064	0.1302		1	0	0.4	-14.07
c.3781A>G	S1261G 2D AIThe SynGAP1 missense variant S1261G is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign; Foldetta results are not available. Overall, the majority of evidence supports a benign impact for S1261G, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.501700	Disordered	0.671500	Binding	0.889	0.574	0.250											-5.042	Likely Benign	0.087	Likely Benign	Likely Benign										0.063	Likely Benign	-0.46	Neutral	0.005	Benign	0.013	Benign	2.32	Pathogenic	0.65	Tolerated			0.2063	0.3477		1	0	0.4	-30.03
c.3796C>G	L1266V 2D AIThe SynGAP1 missense variant L1266V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000											-10.024	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic										0.125	Likely Benign	-2.53	Deleterious	0.995	Probably Damaging	0.890	Possibly Damaging	2.16	Pathogenic	0.00	Affected			0.1301	0.3118		2	1	0.4	-14.03
c.3802C>G	L1268V 2D AIThe SynGAP1 missense variant L1268V 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 flags the variant 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 predicts benign, and the SGM‑Consensus also reports likely benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for the variant, 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	Coiled-coil	0.458154	Structured	0.804315	Binding	0.859	0.629	0.000											-4.137	Likely Benign	0.109	Likely Benign	Likely Benign										0.056	Likely Benign	-0.24	Neutral	0.649	Possibly Damaging	0.157	Benign	2.73	Benign	0.25	Tolerated			0.1331	0.2289		2	1	0.4	-14.03
c.3817C>G	L1273V 2D AIThe SynGAP1 missense variant L1273V is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM, while 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—leans pathogenic (two pathogenic versus one benign vote). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence, particularly the SGM Consensus, indicates 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.			0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500											-6.014	Likely Benign	0.539	Ambiguous	Likely Benign										0.111	Likely Benign	-2.50	Deleterious	0.773	Possibly Damaging	0.287	Benign	2.20	Pathogenic	0.00	Affected			0.1556	0.3178		2	1	0.4	-14.03
c.3850C>G	L1284V 2D AIThe SynGAP1 missense variant L1284V 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		0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875											-4.329	Likely Benign	0.068	Likely Benign	Likely Benign										0.064	Likely Benign	0.90	Neutral	0.008	Benign	0.006	Benign	2.92	Benign	1.00	Tolerated			0.1419	0.1883		2	1	0.4	-14.03
c.3862A>C	K1288Q 2D AIThe SynGAP1 missense variant K1288Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a 2‑to‑2 split and is therefore inconclusive. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence is divided, with an equal number of benign and pathogenic calls, leaving the variant’s clinical significance uncertain. This uncertainty does not contradict ClinVar, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-2.369	Likely Benign	0.172	Likely Benign	Likely Benign										0.173	Likely Benign	-2.51	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.11	Pathogenic	0.00	Affected			0.4149	0.0657		1	1	0.4	-0.04
c.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.3864G>C	K1288N 2D AIThe SynGAP1 missense variant K1288N has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no result for this variant. High‑accuracy assessments therefore show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta as unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3864G>T	K1288N 2D AIThe SynGAP1 missense variant K1288N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy assessments therefore show an uncertain AlphaMissense‑Optimized prediction, a Likely Pathogenic SGM‑Consensus, and no Foldetta data. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.827927	Disordered	0.814714	Binding	0.538	0.784	0.625											-3.670	Likely Benign	0.801	Likely Pathogenic	Ambiguous										0.128	Likely Benign	-4.05	Deleterious	0.991	Probably Damaging	0.987	Probably Damaging	2.10	Pathogenic	0.00	Affected			0.3513	0.1101		1	0	0.4	-14.07
c.3865A>C	K1289Q 2D AIThe SynGAP1 missense variant K1289Q 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 evidence strongly supports a benign classification, and this conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625											-2.940	Likely Benign	0.096	Likely Benign	Likely Benign										0.066	Likely Benign	1.55	Neutral	0.004	Benign	0.004	Benign	3.09	Benign	1.00	Tolerated			0.4002	0.0590		1	1	0.4	-0.04
c.3865A>G	K1289E 2D AIThe SynGAP1 missense variant K1289E is not reported 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 overall consensus of the majority of tools and the high‑accuracy predictions, the variant is most likely benign. 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.	Likely Benign		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625											-3.088	Likely Benign	0.265	Likely Benign	Likely Benign										0.138	Likely Benign	-0.19	Neutral	0.001	Benign	0.002	Benign	2.62	Benign	0.04	Affected			0.3559	0.0514		0	1	0.4	0.94
c.3867G>C	K1289N 2D AIThe SynGAP1 missense variant K1289N is reported in ClinVar as “Not submitted” and is not present in 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) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus also predicts likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, K1289N 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		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625											-4.244	Likely Benign	0.481	Ambiguous	Likely Benign										0.043	Likely Benign	-1.56	Neutral	0.224	Benign	0.120	Benign	2.59	Benign	0.02	Affected			0.3442	0.0940		1	0	0.4	-14.07
c.3867G>T	K1289N 2D AIThe SynGAP1 missense variant K1289N is reported in ClinVar as “Not submitted” and is not present in 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) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, SGM‑Consensus also predicts likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, K1289N 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		0.733139	Disordered	0.828700	Binding	0.548	0.787	0.625											-4.244	Likely Benign	0.481	Ambiguous	Likely Benign										0.043	Likely Benign	-1.56	Neutral	0.224	Benign	0.120	Benign	2.59	Benign	0.02	Affected			0.3442	0.0940		1	0	0.4	-14.07
c.3871C>G	L1291V 2D AIThe SynGAP1 missense variant L1291V 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, so the pathogenic prediction group is empty. High‑accuracy assessments corroborate this benign consensus: 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 prediction aligns with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.863458	Binding	0.579	0.797	0.625											-4.583	Likely Benign	0.103	Likely Benign	Likely Benign										0.028	Likely Benign	0.28	Neutral	0.149	Benign	0.064	Benign	2.61	Benign	0.07	Tolerated			0.1435	0.2946		2	1	0.4	-14.03
c.3874C>G	L1292V 2D AIThe SynGAP1 missense variant L1292V 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		0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625											-4.943	Likely Benign	0.121	Likely Benign	Likely Benign										0.049	Likely Benign	-0.14	Neutral	0.058	Benign	0.038	Benign	2.67	Benign	0.07	Tolerated			0.1769	0.2605		2	1	0.4	-14.03
c.3895C>G	L1299V 2D AIThe SynGAP1 missense variant L1299V 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—there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750											-4.502	Likely Benign	0.121	Likely Benign	Likely Benign										0.385	Likely Benign	-0.02	Neutral	0.124	Benign	0.025	Benign	2.89	Benign	0.09	Tolerated			0.1726	0.3544		2	1	0.4	-14.03
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.3931C>G	L1311V 2D AIThe SynGAP1 missense variant L1311V is catalogued in gnomAD (ID 6‑33451805‑C‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.816150	Disordered	0.968153	Binding	0.393	0.907	0.750								6-33451805-C-G	1	6.20e-7	-3.645	Likely Benign	0.066	Likely Benign	Likely Benign										0.025	Likely Benign	-0.05	Neutral	0.362	Benign	0.193	Benign	2.89	Benign	0.32	Tolerated	3.77	5	0.1666	0.3518		1	2	0.4	-14.03
c.3952C>G	L1318V 2D AIThe SynGAP1 missense variant L1318V is catalogued in gnomAD (ID 6‑33451826‑C‑G) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict the ClinVar record, which contains no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.968271	Binding	0.399	0.865	0.750								6-33451826-C-G	1	6.31e-7	-3.938	Likely Benign	0.091	Likely Benign	Likely Benign										0.038	Likely Benign	-0.58	Neutral	0.113	Benign	0.028	Benign	4.08	Benign	0.75	Tolerated	3.77	5	0.1861	0.3027		1	2	0.4	-14.03
c.397C>G	L133V 2D AIThe SynGAP1 missense variant L133V is not 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 limited: AlphaMissense‑Optimized remains uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign votes); Foldetta results are unavailable. Overall, the majority of evidence (five 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.			0.422041	Structured	0.718429	Binding	0.320	0.896	0.250											-8.429	Likely Pathogenic	0.848	Likely Pathogenic	Ambiguous										0.082	Likely Benign	-1.27	Neutral	0.247	Benign	0.163	Benign	3.61	Benign	0.03	Affected			0.1561	0.1883		2	1	0.4	-14.03
c.3985C>G	L1329V 2D AIThe SynGAP1 missense variant L1329V is catalogued in gnomAD (6‑33451859‑C‑G) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, PROVEAN, ESM1b, and FATHMM, whereas pathogenic calls are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. When predictions are grouped by consensus, the majority of standard algorithms (REVEL, PROVEAN, ESM1b, FATHMM) support a benign effect, while a minority (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default) suggest pathogenicity. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign outcome, and the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also favors benign. 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 benign effect, and this conclusion is consistent with the lack of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875								6-33451859-C-G	1	6.40e-7	-4.209	Likely Benign	0.770	Likely Pathogenic	Likely Benign										0.077	Likely Benign	-1.55	Neutral	0.980	Probably Damaging	0.952	Probably Damaging	3.18	Benign	0.00	Affected	3.77	5	0.1571	0.3579		1	2	0.4	-14.03
c.400A>G	S134G 2D AIThe SynGAP1 missense variant S134G is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus (SGM‑Consensus) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yielding a “Likely Benign” classification. AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple independent predictors and the high‑accuracy consensus indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.447574	Structured	0.695837	Binding	0.333	0.898	0.250											-6.722	Likely Benign	0.457	Ambiguous	Likely Benign										0.120	Likely Benign	-2.19	Neutral	0.034	Benign	0.035	Benign	3.84	Benign	0.00	Affected			0.2268	0.4008		1	0	0.4	-30.03
c.409C>G	L137V 2D AIThe SynGAP1 missense variant L137V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of high‑confidence predictors (six out of nine) indicate a pathogenic impact, whereas three predict benign. Thus, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.621	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic										0.118	Likely Benign	-1.75	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.1533	0.2612		2	1	0.4	-14.03
c.412A>C	K138Q 2D AIThe SynGAP1 missense variant K138Q is not 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. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of tools (five pathogenic vs. four benign) indicate a pathogenic impact. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-8.122	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic										0.173	Likely Benign	-2.15	Neutral	0.700	Possibly Damaging	0.310	Benign	3.58	Benign	0.01	Affected			0.4171	0.1272		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.414A>C	K138N 2D AIThe SynGAP1 missense variant K138N is not 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 a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tool, ESM1b, yields an uncertain result. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K138N 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.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-7.920	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.77	Deleterious	0.700	Possibly Damaging	0.310	Benign	3.56	Benign	0.01	Affected			0.3438	0.1627		1	0	0.4	-14.07
c.414A>T	K138N 2D AIThe SynGAP1 missense variant K138N is not 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 a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tool, ESM1b, yields an uncertain result. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors pathogenicity. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that K138N 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.			0.590140	Disordered	0.619482	Binding	0.349	0.901	0.375											-7.920	In-Between	0.999	Likely Pathogenic	Likely Pathogenic										0.093	Likely Benign	-2.77	Deleterious	0.700	Possibly Damaging	0.310	Benign	3.56	Benign	0.01	Affected			0.3438	0.1627		1	0	0.4	-14.07
c.415A>G	S139G 2D AIThe SynGAP1 missense variant S139G is not reported in ClinVar and is absent from gnomAD, indicating no documented clinical or population data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus, also reports the variant as Likely Benign, and AlphaMissense‑Optimized confirms a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.553315	Disordered	0.600637	Binding	0.353	0.900	0.250											1.647	Likely Benign	0.159	Likely Benign	Likely Benign										0.116	Likely Benign	1.29	Neutral	0.000	Benign	0.000	Benign	4.29	Benign	1.00	Tolerated			0.2712	0.3414		1	0	0.4	-30.03
c.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.424A>G	K142E 2D AIThe SynGAP1 missense variant K142E is not reported in ClinVar (no ClinVar entry) and is absent from 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 effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts Pathogenic, and the SGM‑Consensus (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 predictions point to a pathogenic effect, 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-14.450	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.249	Likely Benign	-2.59	Deleterious	0.247	Benign	0.125	Benign	3.49	Benign	0.00	Affected			0.3644	0.0952		0	1	0.4	0.94
c.426A>C	K142N 2D AIThe SynGAP1 missense variant K142N is not 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.169	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.097	Likely Benign	-3.13	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.47	Benign	0.00	Affected			0.3586	0.1437		1	0	0.4	-14.07
c.426A>T	K142N 2D AIThe SynGAP1 missense variant K142N is not 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		0.461924	Structured	0.558796	Binding	0.374	0.859	0.500											-12.169	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic										0.096	Likely Benign	-3.13	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.47	Benign	0.00	Affected			0.3586	0.1437		1	0	0.4	-14.07
c.433A>C	K145Q 2D AIThe SynGAP1 missense variant K145Q is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Computational predictions are split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy tools give no definitive verdict: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Consequently, the variant is neither clearly benign nor pathogenic according to current predictions, and there is no ClinVar annotation to contradict this ambiguous computational assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-9.676	Likely Pathogenic	0.955	Likely Pathogenic	Ambiguous										0.163	Likely Benign	-2.34	Neutral	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.4233	0.1478		1	1	0.4	-0.04
c.433A>G	K145E 2D AIThe SynGAP1 missense variant K145E 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, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions arise from PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of high‑confidence tools predict a pathogenic impact, and this conclusion does not contradict any ClinVar annotation (none is present). Thus, the variant is most likely pathogenic. 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											-12.571	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.245	Likely Benign	-2.51	Deleterious	0.247	Benign	0.125	Benign	3.68	Benign	0.00	Affected			0.3638	0.1179		0	1	0.4	0.94
c.435G>C	K145N 2D AIThe SynGAP1 missense variant K145N is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (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 evidence points toward a pathogenic impact for K145N, 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		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.718	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.109	Likely Benign	-2.76	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.3430	0.1832		1	0	0.4	-14.07
c.435G>T	K145N 2D AIThe SynGAP1 missense variant K145N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL (score 0.45), polyPhen‑2 HumVar (benign), and FATHMM (benign). Pathogenic predictions arise from PROVEAN (deleterious), polyPhen‑2 HumDiv (probably damaging), SIFT (deleterious), ESM1b (damaging), AlphaMissense‑Default (pathogenic), and AlphaMissense‑Optimized (pathogenic). The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.671169	Disordered	0.516174	Binding	0.321	0.835	0.625											-8.718	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.109	Likely Benign	-2.76	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.65	Benign	0.00	Affected			0.3430	0.1832		1	0	0.4	-14.07
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.445A>G	K149E 2D AIThe SynGAP1 missense variant K149E is not 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, yields an equal split (2 vs 2) and is therefore considered unavailable. AlphaMissense‑Optimized, a high‑accuracy predictor, classifies the variant as pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard tools (five benign vs. four pathogenic) lean toward a benign interpretation, 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.			0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-12.148	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.231	Likely Benign	-2.17	Neutral	0.141	Benign	0.062	Benign	3.59	Benign	0.00	Affected			0.4636	0.1022		0	1	0.4	0.94
c.447A>C	K149N 2D AIThe SynGAP1 missense variant K149N is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. In contrast, tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a majority pathogenic vote (3 pathogenic vs. 1 benign) and is labeled “Likely Pathogenic.” AlphaMissense‑Optimized independently predicts pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of computational evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-9.275	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.121	Likely Benign	-2.85	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.00	Affected			0.4427	0.1559		1	0	0.4	-14.07
c.447A>T	K149N 2D AIThe SynGAP1 missense variant K149N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL, 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 K149N, 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		0.562014	Disordered	0.501681	Binding	0.302	0.839	0.625											-9.275	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic										0.121	Likely Benign	-2.85	Deleterious	0.141	Benign	0.123	Benign	3.56	Benign	0.00	Affected			0.4427	0.1559		1	0	0.4	-14.07
c.448C>G	L150V 2D AIThe SynGAP1 missense variant L150V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.375	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.84	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.1473	0.3178		2	1	0.4	-14.03
c.460A>G	S154G 2D AIThe SynGAP1 missense variant S154G is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500											-5.482	Likely Benign	0.115	Likely Benign	Likely Benign										0.074	Likely Benign	-0.83	Neutral	0.006	Benign	0.008	Benign	4.05	Benign	0.11	Tolerated			0.2790	0.3944		1	0	0.4	-30.03
c.463A>G	S155G 2D AIThe SynGAP1 missense variant S155G is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools specifically indicate a benign outcome from AlphaMissense‑Optimized, while SGM Consensus and Foldetta are unavailable. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.515359	Binding	0.292	0.787	0.500											-9.243	Likely Pathogenic	0.628	Likely Pathogenic	Likely Benign										0.152	Likely Benign	-1.84	Neutral	0.956	Probably Damaging	0.931	Probably Damaging	3.81	Benign	0.00	Affected			0.2416	0.3976		1	0	0.4	-30.03
c.478C>G	L160V 2D AIThe SynGAP1 missense variant L160V is not 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. three pathogenic) indicate that the variant is most likely benign. This conclusion is consistent with the lack of ClinVar evidence and gnomAD presence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.454136	Structured	0.526760	Binding	0.275	0.728	0.125											-12.506	Likely Pathogenic	0.729	Likely Pathogenic	Likely Benign										0.055	Likely Benign	-1.44	Neutral	0.247	Benign	0.113	Benign	3.90	Benign	0.00	Affected			0.1553	0.3319		2	1	0.4	-14.03
c.493A>G	S165G 2D AIThe SynGAP1 missense variant S165G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.429200	Structured	0.509123	Binding	0.324	0.644	0.250											-7.691	In-Between	0.223	Likely Benign	Likely Benign										0.182	Likely Benign	-1.17	Neutral	0.272	Benign	0.086	Benign	3.99	Benign	0.00	Affected			0.2622	0.4441		1	0	0.4	-30.03
c.4A>G	S2G 2D AIThe SynGAP1 missense variant S2G is reported in gnomAD (ID 6‑33420268‑A‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for this variant, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.543646	Binding	0.382	0.922	0.750								6-33420268-A-G	1	6.58e-7	-4.273	Likely Benign	0.124	Likely Benign	Likely Benign										0.079	Likely Benign	-0.48	Neutral	0.012	Benign	0.002	Benign	4.10	Benign	0.00	Affected	4.32	1	0.2872	0.5495		0	1	0.4	-30.03
c.517C>G	L173V 2D AIThe SynGAP1 missense variant L173V is not 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. Only ESM1b predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375											-8.320	Likely Pathogenic	0.495	Ambiguous	Likely Benign										0.100	Likely Benign	-0.95	Neutral	0.131	Benign	0.058	Benign	4.05	Benign	0.22	Tolerated			0.1343	0.3217		2	1	0.4	-14.03
c.526A>G	S176G 2D AIThe SynGAP1 missense variant S176G is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33435168‑A‑G). Consensus among most in silico predictors is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all report a benign effect. No tool predicts pathogenicity. Two predictors are inconclusive: ESM1b and AlphaMissense‑Default, which are grouped under uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains uncertain, and Foldetta stability analysis is unavailable. Overall, the computational evidence overwhelmingly favors a benign impact, which does not contradict the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.466016	Uncertain	0.380	0.597	0.375					Uncertain		1	6-33435168-A-G	1	6.20e-7	-7.541	In-Between	0.360	Ambiguous	Likely Benign										0.066	Likely Benign	-1.08	Neutral	0.131	Benign	0.039	Benign	4.08	Benign	0.22	Tolerated	3.54	6	0.2361	0.3414		0	1	0.4	-30.03
c.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.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.534G>C	K178N 2D AIThe SynGAP1 missense variant K178N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN)—all predict it to be pathogenic or likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus reports Likely Pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of pathogenic predictions, K178N 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		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-12.137	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.32	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.86	Benign	0.01	Affected			0.4503	0.1321		1	0	0.4	-14.07
c.534G>T	K178N 2D AIThe SynGAP1 missense variant K178N 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 (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates it is likely pathogenic, and Foldetta’s protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy tools’ results, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.455271	Uncertain	0.354	0.622	0.375											-12.137	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic										0.131	Likely Benign	-3.32	Deleterious	0.971	Probably Damaging	0.598	Possibly Damaging	3.86	Benign	0.01	Affected			0.4503	0.1321		1	0	0.4	-14.07
c.556T>G	L186V 2D AIThe SynGAP1 missense variant L186V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear majority and is therefore unavailable; Foldetta results are also unavailable. Overall, the majority of available predictions (five pathogenic vs. four benign) indicate a pathogenic effect. There is no ClinVar entry to contradict this assessment, so the variant is most likely pathogenic based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.458154	Structured	0.428613	Uncertain	0.397	0.617	0.500											-9.385	Likely Pathogenic	0.958	Likely Pathogenic	Likely Pathogenic										0.090	Likely Benign	-2.27	Neutral	0.734	Possibly Damaging	0.185	Benign	3.60	Benign	0.00	Affected			0.1419	0.3665		2	1	0.4	-14.03
c.559C>G	L187V 2D AIThe SynGAP1 missense variant L187V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs. two benign). High‑accuracy AlphaMissense‑Optimized predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the majority of standard predictors lean toward a benign classification, but the single high‑accuracy tool indicates pathogenicity. Thus, the variant is most likely benign based on the collective evidence, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375											-10.543	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic										0.136	Likely Benign	-2.24	Neutral	0.437	Benign	0.079	Benign	3.81	Benign	0.02	Affected			0.1525	0.3509		2	1	0.4	-14.03
c.562A>G	S188G 2D AIThe SynGAP1 missense variant S188G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM‑Consensus) derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is “Likely Pathogenic.” AlphaMissense‑Optimized returns an uncertain result, and Foldetta (which would combine FoldX‑MD and Rosetta outputs) has no available data for this variant. Based on the overall distribution of predictions, the variant is most likely pathogenic; this assessment does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.428502	Uncertain	0.298	0.603	0.500											-10.113	Likely Pathogenic	0.919	Likely Pathogenic	Ambiguous										0.123	Likely Benign	-3.10	Deleterious	0.882	Possibly Damaging	0.404	Benign	3.91	Benign	0.00	Affected			0.3045	0.5542		1	0	0.4	-30.03
c.568A>G	S190G 2D AIThe SynGAP1 missense variant S190G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250											-5.440	Likely Benign	0.321	Likely Benign	Likely Benign										0.048	Likely Benign	-1.26	Neutral	0.243	Benign	0.079	Benign	4.11	Benign	0.19	Tolerated			0.2780	0.4765		1	0	0.4	-30.03
c.571A>G	S191G 2D AIThe SynGAP1 missense variant S191G is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also leans toward benign (two benign versus two uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S191G is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125											-7.161	In-Between	0.506	Ambiguous	Likely Benign										0.173	Likely Benign	-2.43	Neutral	0.131	Benign	0.058	Benign	3.77	Benign	0.03	Affected			0.2893	0.5335		1	0	0.4	-30.03
c.586T>G	L196V 2D AIThe SynGAP1 missense variant L196V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, 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, the majority of evidence (five benign vs three pathogenic) points to a benign impact. This conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.284882	Structured	0.429452	Uncertain	0.489	0.521	0.125											-8.702	Likely Pathogenic	0.898	Likely Pathogenic	Ambiguous										0.106	Likely Benign	-2.31	Neutral	0.243	Benign	0.097	Benign	3.71	Benign	0.01	Affected			0.1436	0.2850		2	1	0.4	-14.03
c.592C>G	L198V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L198V variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (3 pathogenic vs. 1 benign) indicates pathogenicity; Foldetta remains uncertain. Overall, the majority of evaluated tools predict a pathogenic impact, and this is not contradicted by any ClinVar annotation (none exists). Thus, the variant is most likely pathogenic based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-9.343	Likely Pathogenic	0.747	Likely Pathogenic	Likely Benign	1.10	Ambiguous	0.2	1.24	Ambiguous	1.17	Ambiguous	0.34	Likely Benign	0.265	Likely Benign	-2.54	Deleterious	0.990	Probably Damaging	0.675	Possibly Damaging	3.44	Benign	0.00	Affected			0.1520	0.3017		2	1	0.4	-14.03
c.598T>G	L200V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L200V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic outcome are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and the Foldetta stability assessment. Uncertain results come from Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as pathogenic. Overall, the majority of evidence points to a benign effect; there is no ClinVar annotation to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.366687	Structured	0.428168	Uncertain	0.687	0.453	0.125											-6.917	Likely Benign	0.213	Likely Benign	Likely Benign	2.15	Destabilizing	0.2	1.85	Ambiguous	2.00	Destabilizing	0.92	Ambiguous	0.098	Likely Benign	-1.07	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	4.09	Benign	0.24	Tolerated			0.1593	0.3607		2	1	0.4	-14.03
c.619A>C	K207Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K207Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from REVEL, SIFT, and FATHMM; pathogenic predictions from SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. High‑accuracy assessments give a mixed picture: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; AlphaMissense‑Optimized is uncertain; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign impact. Folding‑stability scores from FoldX and Rosetta are inconclusive, and premPS is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-9.544	Likely Pathogenic	0.874	Likely Pathogenic	Ambiguous	0.57	Ambiguous	0.1	-0.57	Ambiguous	0.00	Likely Benign	0.61	Ambiguous	0.250	Likely Benign	-2.95	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	4.00	Benign	0.10	Tolerated			0.4010	0.1797		1	1	0.4	-0.04
c.619A>G	K207E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K207E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a larger group predicts pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. The remaining stability predictions (FoldX and Rosetta) are uncertain. Overall, the majority of evidence points to a pathogenic effect for K207E, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-14.387	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.39	Ambiguous	0.1	1.21	Ambiguous	1.30	Ambiguous	1.09	Destabilizing	0.265	Likely Benign	-3.00	Deleterious	0.982	Probably Damaging	0.679	Possibly Damaging	4.02	Benign	0.07	Tolerated			0.3504	0.1557		0	1	0.4	0.94
c.621G>C	K207N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K207N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: SGM‑Consensus, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicating likely pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the preponderance of evidence points to a pathogenic effect for K207N, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.881	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	1.48	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.123	Likely Benign	-3.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.98	Benign	0.07	Tolerated			0.3184	0.2335		1	0	0.4	-14.07
c.621G>T	K207N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K207N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions arise from premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, and the SGM Consensus (majority vote) also predicts Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence indicates that K207N is most likely pathogenic, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.374039	Structured	0.406823	Uncertain	0.847	0.359	0.125											-12.881	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	1.48	Ambiguous	1.10	Ambiguous	1.00	Destabilizing	0.124	Likely Benign	-3.54	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	3.98	Benign	0.07	Tolerated			0.3184	0.2335		1	0	0.4	-14.07
c.631A>G	S211G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211G is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are premPS, PROVEAN, polyPhen‑2 HumDiv, and ESM1b; Rosetta is uncertain. High‑accuracy methods give a benign result for AlphaMissense‑Optimized and for Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs two pathogenic). No evidence from ClinVar contradicts these predictions. Overall, the balance of evidence—including the unanimous benign calls from the high‑accuracy tools—suggests that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125											-9.895	Likely Pathogenic	0.265	Likely Benign	Likely Benign	0.30	Likely Benign	0.2	0.54	Ambiguous	0.42	Likely Benign	1.07	Destabilizing	0.067	Likely Benign	-3.17	Deleterious	0.787	Possibly Damaging	0.404	Benign	3.92	Benign	0.07	Tolerated			0.2560	0.4337		1	0	0.4	-30.03
c.640C>G	L214V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L214V is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The remaining methods—FoldX, Rosetta, premPS, and AlphaMissense‑Optimized—yield uncertain results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as uncertain. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125											-9.913	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	1.80	Ambiguous	0.4	0.54	Ambiguous	1.17	Ambiguous	0.89	Ambiguous	0.495	Likely Benign	-2.54	Deleterious	0.384	Benign	0.070	Benign	5.78	Benign	0.01	Affected			0.1469	0.3887		2	1	0.4	-14.03
c.685A>C	K229Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K229Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, FATHMM, and Foldetta; pathogenic predictions arise from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. Overall, the preponderance of evidence indicates the variant is most likely pathogenic, and this assessment does not conflict with ClinVar status, which currently has no entry for K229Q. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-9.606	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.41	Likely Benign	0.0	-0.05	Likely Benign	0.18	Likely Benign	0.55	Ambiguous	0.813	Likely Pathogenic	-3.03	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	5.84	Benign	0.02	Affected			0.4456	0.1057		1	1	0.4	-0.04
c.685A>G	K229E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K229E is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include FoldX, Rosetta, premPS, SIFT, and FATHMM. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall distribution of predictions, the variant is most likely pathogenic; this conclusion does not contradict the ClinVar status, which currently has no entry for K229E. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-12.828	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.47	Likely Benign	0.0	0.24	Likely Benign	0.36	Likely Benign	0.18	Likely Benign	0.816	Likely Pathogenic	-3.10	Deleterious	0.993	Probably Damaging	0.971	Probably Damaging	5.84	Benign	0.09	Tolerated			0.3915	0.0793		0	1	0.4	0.94
c.687A>C	K229N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K229N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. Four tools (FoldX, Rosetta, Foldetta, premPS) return uncertain results and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect. The variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-13.620	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.82	Ambiguous	0.1	0.64	Ambiguous	0.73	Ambiguous	0.61	Ambiguous	0.590	Likely Pathogenic	-3.79	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	5.83	Benign	0.01	Affected			0.3682	0.1013		1	0	0.4	-14.07
c.687A>T	K229N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K229N missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining nine tools—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is uncertain and therefore not considered evidence for or against pathogenicity. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.179055	Structured	0.310912	Uncertain	0.843	0.306	0.000											-13.620	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.82	Ambiguous	0.1	0.64	Ambiguous	0.73	Ambiguous	0.61	Ambiguous	0.588	Likely Pathogenic	-3.79	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	5.83	Benign	0.01	Affected			0.3682	0.1013		1	0	0.4	-14.07
c.721A>C	K241Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K241Q missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, FATHMM, and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, nine tools predict pathogenicity versus four predicting benign, with no ClinVar evidence to contradict these findings. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.593	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.33	Likely Benign	0.0	0.46	Likely Benign	0.40	Likely Benign	0.63	Ambiguous	0.767	Likely Pathogenic	-3.33	Deleterious	0.995	Probably Damaging	0.914	Probably Damaging	5.83	Benign	0.04	Affected			0.4225	0.1527		1	1	0.4	-0.04
c.721A>G	K241E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K241E missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include SIFT and FATHMM, whereas a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-12.582	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.75	Ambiguous	0.1	1.36	Ambiguous	1.06	Ambiguous	0.68	Ambiguous	0.878	Likely Pathogenic	-3.43	Deleterious	0.982	Probably Damaging	0.679	Possibly Damaging	6.00	Benign	0.10	Tolerated			0.3610	0.1179		0	1	0.4	0.94
c.723A>C	K241N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is inconclusive. 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	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.198	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.13	Ambiguous	1.03	Ambiguous	0.89	Ambiguous	0.663	Likely Pathogenic	-4.23	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.81	Benign	0.03	Affected			0.3426	0.1872		1	0	0.4	-14.07
c.723A>T	K241N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K241N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain results are reported for FoldX, Rosetta, Foldetta, and premPS and are not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.196879	Structured	0.349250	Uncertain	0.797	0.347	0.000											-10.198	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.92	Ambiguous	0.1	1.13	Ambiguous	1.03	Ambiguous	0.89	Ambiguous	0.663	Likely Pathogenic	-4.23	Deleterious	0.995	Probably Damaging	0.829	Possibly Damaging	5.81	Benign	0.03	Affected			0.3426	0.1872		1	0	0.4	-14.07
c.736C>G	L246V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L246V is reported in gnomAD (variant ID 6‑33435587‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Only FATHMM predicts a benign outcome. Uncertain results are reported by Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. The overwhelming majority of evidence points to a pathogenic impact, and this conclusion is not contradicted by ClinVar, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.472492	Structured	0.302312	Uncertain	0.859	0.364	0.000								6-33435587-C-G	1	6.20e-7	-12.092	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	2.09	Destabilizing	0.1	1.52	Ambiguous	1.81	Ambiguous	1.13	Destabilizing	0.736	Likely Pathogenic	-2.60	Deleterious	0.930	Possibly Damaging	0.504	Possibly Damaging	4.71	Benign	0.01	Affected	3.41	14	0.1434	0.3607		1	2	0.4	-14.03
c.751A>C	K251Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K251Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar, while premPS and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Taken together, the majority of evidence supports a benign classification for K251Q, and this conclusion does not contradict the absence of a ClinVar entry. Based on the aggregate predictions, K251Q is most likely benign, and this is consistent with its absence from ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-5.869	Likely Benign	0.362	Ambiguous	Likely Benign	0.36	Likely Benign	0.1	0.42	Likely Benign	0.39	Likely Benign	-0.62	Ambiguous	0.465	Likely Benign	0.55	Neutral	0.997	Probably Damaging	0.879	Possibly Damaging	5.86	Benign	0.63	Tolerated			0.4466	0.1085		1	1	0.4	-0.04
c.751A>G	K251E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K251E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS, PROVEAN, SIFT, and FATHMM, while those that agree on a pathogenic effect are REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give uncertain results. High‑accuracy methods are likewise inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and Foldetta is uncertain. Overall, the majority of available predictions lean toward pathogenicity, with a small but notable benign signal. Therefore, 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.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-12.812	Likely Pathogenic	0.906	Likely Pathogenic	Ambiguous	0.88	Ambiguous	0.2	0.99	Ambiguous	0.94	Ambiguous	0.40	Likely Benign	0.571	Likely Pathogenic	-0.54	Neutral	0.970	Probably Damaging	0.584	Possibly Damaging	5.80	Benign	0.46	Tolerated			0.3929	0.0860		0	1	0.4	0.94
c.753G>C	K251N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K251N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM (nine tools). Only AlphaMissense‑Default predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the preponderance of evidence indicates that K251N is most likely benign, and this conclusion does not contradict the current ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-7.978	In-Between	0.930	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.1	0.21	Likely Benign	0.25	Likely Benign	0.32	Likely Benign	0.298	Likely Benign	-1.29	Neutral	0.384	Benign	0.070	Benign	5.73	Benign	0.39	Tolerated			0.3848	0.1196		1	0	0.4	-14.07
c.753G>T	K251N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K251N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM (nine tools). Only AlphaMissense‑Default predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign consensus; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the preponderance of evidence indicates that K251N is most likely benign, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125											-7.978	In-Between	0.930	Likely Pathogenic	Ambiguous	0.29	Likely Benign	0.1	0.21	Likely Benign	0.25	Likely Benign	0.32	Likely Benign	0.298	Likely Benign	-1.29	Neutral	0.384	Benign	0.070	Benign	5.73	Benign	0.39	Tolerated			0.3848	0.1196		1	0	0.4	-14.07
c.760A>C	K254Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K254Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, SIFT, and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Two tools, Rosetta and premPS, give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. No prediction or folding stability result is missing or inconclusive. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375											-12.332	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.13	Likely Benign	0.1	-0.61	Ambiguous	-0.24	Likely Benign	0.90	Ambiguous	0.737	Likely Pathogenic	-3.04	Deleterious	0.997	Probably Damaging	0.879	Possibly Damaging	5.91	Benign	0.11	Tolerated			0.3749	0.1483		1	1	0.4	-0.04
c.760A>G	K254E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K254E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: FATHMM is the sole benign predictor, while the remaining 13 tools (REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and SGM‑Consensus) predict pathogenicity; FoldX and Foldetta are uncertain. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized indicates pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. Overall, the preponderance of evidence supports a pathogenic classification for K254E, and this conclusion 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	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375											-14.745	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.72	Ambiguous	0.1	2.34	Destabilizing	1.53	Ambiguous	1.17	Destabilizing	0.860	Likely Pathogenic	-3.27	Deleterious	0.970	Probably Damaging	0.584	Possibly Damaging	5.87	Benign	0.05	Affected			0.3224	0.1352		0	1	0.4	0.94
c.762G>C	K254N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K254N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that classify the variant as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The majority of other in silico predictors—REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—indicate a pathogenic effect. Stability‑based methods FoldX, Rosetta, and Foldetta returned uncertain results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as unavailable. Overall, the preponderance of evidence supports a pathogenic classification, which contradicts the current ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375					Uncertain		1				-13.306	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.73	Ambiguous	0.2	1.87	Ambiguous	1.30	Ambiguous	1.19	Destabilizing	0.757	Likely Pathogenic	-4.23	Deleterious	0.384	Benign	0.070	Benign	5.93	Benign	0.01	Affected	3.39	15	0.3200	0.1488		1	0	0.4	-14.07	215.3	-21.0	-1.0	1.7	0.2	0.3		X						Potentially Pathogenic	The amino group of Lys254, located in an α-β loop connecting the PH and C2 domains (res. Lys251-Arg258), forms salt bridges with the carboxylate groups of Glu244 and Asp684. Since the neutral carboxamide group of the Asn254 side chain cannot form salt bridges with acidic residues, the residue swap potentially weakens the tertiary structure assembly and/or influences the loop positioning. Regardless, in both the variant and WT simulations, all hydrogen bonds formed by the residue’s side chain were broken, and the residue rotated outwards. The partially α helical conformation of the loop, which extends to a nearby α helix (res. Met414-Asn426), is dynamic, making it unclear if the mutation affects it.
c.762G>T	K254N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K254N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic” (3 pathogenic vs. 1 benign). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from FoldX or Rosetta alone is conclusive. Based on the overall pattern of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not currently catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.513880	Disordered	0.207751	Uncertain	0.799	0.285	0.375											-13.306	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.73	Ambiguous	0.2	1.87	Ambiguous	1.30	Ambiguous	1.19	Destabilizing	0.757	Likely Pathogenic	-4.23	Deleterious	0.384	Benign	0.070	Benign	5.93	Benign	0.01	Affected	3.39	15	0.3200	0.1488		1	0	0.4	-14.07	215.3	-21.0	-1.0	1.7	0.2	0.3		X						Potentially Pathogenic	The amino group of Lys254, located in an α-β loop connecting the PH and C2 domains (res. Lys251-Arg258), forms salt bridges with the carboxylate groups of Glu244 and Asp684. Since the neutral carboxamide group of the Asn254 side chain cannot form salt bridges with acidic residues, the residue swap potentially weakens the tertiary structure assembly and/or influences the loop positioning. Regardless, in both the variant and WT simulations, all hydrogen bonds formed by the residue’s side chain were broken, and the residue rotated outwards. The partially α helical conformation of the loop, which extends to a nearby α helix (res. Met414-Asn426), is dynamic, making it unclear if the mutation affects it.
c.769A>G	S257G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S257G is not reported in ClinVar (ClinVar status: None) and has no entry in gnomAD (gnomAD status: None). Prediction tools that agree on a benign effect include SIFT, FATHMM, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support this view: AlphaMissense‑Optimized indicates a benign change, whereas the SGM‑Consensus (majority vote) indicates likely pathogenic. The Foldetta stability prediction is unavailable and therefore does not influence the overall assessment. Based on the preponderance of pathogenic predictions and the lack of any ClinVar annotation, the variant is most likely pathogenic, with no contradiction from existing ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.384043	Structured	0.258293	Uncertain	0.847	0.272	0.250											-11.206	Likely Pathogenic	0.624	Likely Pathogenic	Likely Benign	0.61	Ambiguous	0.3	0.60	Ambiguous	0.61	Ambiguous	0.62	Ambiguous	0.703	Likely Pathogenic	-2.95	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	5.79	Benign	0.11	Tolerated			0.2087	0.3589		1	0	0.4	-30.03
c.790C>G	L264V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L264V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized; all other evaluated algorithms (SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic or likely pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as Pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for L264V, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000											-10.621	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	2.55	Destabilizing	0.1	1.62	Ambiguous	2.09	Destabilizing	1.24	Destabilizing	0.444	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	0.73	Pathogenic	0.01	Affected			0.1280	0.2289		2	1	0.4	-14.03
c.793A>C	K265Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K265Q is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Among standard in‑silico predictors, five tools (REVEL, FoldX, PROVEAN, AlphaMissense‑Optimized, Foldetta) predict a benign effect, while five (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM) predict pathogenicity. Three tools (premPS, AlphaMissense‑Default, Rosetta) are inconclusive. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a pathogenic consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and a benign outcome from Foldetta. Overall, the predictions are mixed; the balance of evidence, including the two high‑confidence benign calls, suggests the variant is more likely benign, and this does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.533	Likely Pathogenic	0.505	Ambiguous	Likely Benign	0.35	Likely Benign	0.1	-1.15	Ambiguous	-0.40	Likely Benign	0.80	Ambiguous	0.386	Likely Benign	-2.46	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	1.85	Pathogenic	0.05	Affected			0.4401	0.1062		1	1	0.4	-0.04
c.793A>G	K265E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265E missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, and Foldetta. Those that agree on a pathogenic effect include SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, FoldX, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evaluated tools (eight pathogenic vs. three benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-12.163	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.63	Ambiguous	0.2	0.00	Likely Benign	0.32	Likely Benign	0.95	Ambiguous	0.461	Likely Benign	-2.79	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.94	Pathogenic	0.05	Affected			0.3801	0.0882		0	1	0.4	0.94
c.795G>C	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, whereas the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain results are reported by FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.350	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.795G>T	K265N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K265N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and Rosetta, while the majority of algorithms predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). Uncertain or inconclusive results are reported only for FoldX, Foldetta, and premPS, and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.209395	Structured	0.309758	Uncertain	0.936	0.275	0.000											-8.759	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.98	Ambiguous	0.1	0.16	Likely Benign	0.57	Ambiguous	0.85	Ambiguous	0.351	Likely Benign	-3.26	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.86	Pathogenic	0.03	Affected			0.3691	0.1158		1	0	0.4	-14.07
c.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.820C>G	L274V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L274V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise FoldX, Rosetta, Foldetta, 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, is classified as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while both the SGM‑Consensus and Foldetta (combining FoldX‑MD and Rosetta outputs) predict pathogenicity. No predictions are missing or inconclusive. Overall, the preponderance of evidence from multiple independent tools points to a pathogenic impact for L274V. This conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.066181	Structured	0.377483	Uncertain	0.866	0.195	0.250											-5.634	Likely Benign	0.593	Likely Pathogenic	Likely Benign	2.13	Destabilizing	0.6	2.22	Destabilizing	2.18	Destabilizing	0.99	Ambiguous	0.378	Likely Benign	-2.56	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	0.10	Pathogenic	0.02	Affected			0.1448	0.1860		2	1	0.4	-14.03
c.829A>C	K277Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K277Q is reported in gnomAD (ID 6‑33437734‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions from FoldX, Foldetta, and premPS; pathogenic predictions from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points toward a pathogenic effect, with only a minority of tools indicating benign or uncertain outcomes. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250								6-33437734-A-C	1	6.20e-7	-12.547	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.03	Likely Benign	0.1	0.63	Ambiguous	0.33	Likely Benign	0.42	Likely Benign	0.655	Likely Pathogenic	-3.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.02	Affected	3.38	19	0.4000	0.0672		1	1	0.4	-0.04
c.829A>G	K277E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K277E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, and Foldetta. Tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. No predictions are missing or inconclusive. Overall, the majority of tools (10/13) predict pathogenicity, whereas only three predict benign. Therefore, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-14.886	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	-0.14	Likely Benign	0.1	0.18	Likely Benign	0.02	Likely Benign	0.51	Ambiguous	0.694	Likely Pathogenic	-3.68	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.85	Pathogenic	0.01	Affected			0.3462	0.0492		0	1	0.4	0.94
c.831G>C	K277N 2D AIThe SynGAP1 missense variant K277N is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and premPS. Tools that predict pathogenicity are SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as Benign. No predictions are missing or inconclusive. Overall, the majority of tools (10/14) predict pathogenicity, whereas four tools predict benign. Therefore, the variant is most likely pathogenic based on current computational evidence, and this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-9.646	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.4	0.08	Likely Benign	0.01	Likely Benign	0.46	Likely Benign	0.572	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.03	Affected			0.3265	0.0568		1	0	0.4	-14.07
c.831G>T	K277N 2D AIThe SynGAP1 missense variant K277N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, and premPS. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also likely pathogenic; Foldetta, a protein‑folding stability predictor, reports a benign effect. Overall, the preponderance of evidence (10 pathogenic vs. 4 benign predictions) points to a pathogenic classification. This conclusion is not contradicted by ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.061840	Structured	0.321811	Uncertain	0.649	0.247	0.250											-9.646	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	-0.07	Likely Benign	0.4	0.08	Likely Benign	0.01	Likely Benign	0.46	Likely Benign	0.572	Likely Pathogenic	-4.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.03	Affected			0.3265	0.0568		1	0	0.4	-14.07
c.832A>C	K278Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, whereas Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts a benign effect, and AlphaMissense‑Optimized remains uncertain. Overall, the majority of evidence points to a pathogenic impact for K278Q, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-11.107	Likely Pathogenic	0.902	Likely Pathogenic	Ambiguous	0.23	Likely Benign	0.1	0.25	Likely Benign	0.24	Likely Benign	0.73	Ambiguous	0.387	Likely Benign	-3.63	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.71	Pathogenic	0.05	Affected			0.3770	0.0672		1	1	0.4	-0.04
c.832A>G	K278E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and SIFT, all of which score the substitution as tolerated. In contrast, a majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic verdict. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, predicts a benign effect. premPS is inconclusive and therefore not considered evidence. High‑accuracy assessments therefore show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as pathogenic, and Foldetta as benign. Overall, the preponderance of evidence from multiple independent predictors indicates that K278E is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-14.047	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.1	0.39	Likely Benign	0.40	Likely Benign	0.68	Ambiguous	0.463	Likely Benign	-3.64	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.76	Pathogenic	0.06	Tolerated			0.3189	0.0492		0	1	0.4	0.94
c.834G>C	K278N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K278N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts benign. Overall, the majority of tools support a pathogenic effect, so the variant is most likely pathogenic; this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.834G>T	K278N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K278N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas tools that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With a majority of evidence pointing to deleterious effects and no ClinVar annotation to contradict, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.120615	Structured	0.310130	Uncertain	0.748	0.253	0.125											-10.611	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.40	Likely Benign	0.0	0.05	Likely Benign	0.23	Likely Benign	0.44	Likely Benign	0.255	Likely Benign	-4.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.81	Pathogenic	0.07	Tolerated			0.3071	0.0568		1	0	0.4	-14.07
c.850C>G	L284V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L284V missense variant has no ClinVar entry and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Predictions that are uncertain or inconclusive are FoldX, AlphaMissense‑Default, and Foldetta. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta remains uncertain. Overall, the balance of evidence leans toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000											-6.726	Likely Benign	0.347	Ambiguous	Likely Benign	1.65	Ambiguous	0.2	2.08	Destabilizing	1.87	Ambiguous	1.38	Destabilizing	0.248	Likely Benign	-2.32	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.03	Affected			0.1259	0.2456		2	1	0.4	-14.03
c.856C>G	L286V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L286V 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 only AlphaMissense‑Optimized, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—consistently predict a pathogenic impact; AlphaMissense‑Default and Rosetta are uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized indicates benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.122885	Structured	0.385647	Uncertain	0.932	0.260	0.000											-9.986	Likely Pathogenic	0.500	Ambiguous	Likely Benign	2.44	Destabilizing	0.5	1.63	Ambiguous	2.04	Destabilizing	1.26	Destabilizing	0.676	Likely Pathogenic	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.71	Pathogenic	0.01	Affected			0.1492	0.3007		2	1	0.4	-14.03
c.868C>G	L290V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L290V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and Rosetta, whereas a majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Predictions that are inconclusive or unavailable are FoldX, premPS, ESM1b, AlphaMissense‑Optimized, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple pathogenic‑predicting tools and the SGM Consensus suggests 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	0.127496	Structured	0.399723	Uncertain	0.904	0.255	0.000											-7.392	In-Between	0.834	Likely Pathogenic	Ambiguous	1.17	Ambiguous	0.1	0.35	Likely Benign	0.76	Ambiguous	0.62	Ambiguous	0.366	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.98	Pathogenic	0.05	Affected			0.1574	0.4177		2	1	0.4	-14.03
c.889A>C	K297Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K297Q missense variant is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, Rosetta, and Foldetta. In contrast, the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX is uncertain and is treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as benign. Overall, the preponderance of evidence points to a pathogenic effect for K297Q. This conclusion is not contradicted by ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-8.393	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.66	Ambiguous	0.3	0.14	Likely Benign	0.40	Likely Benign	1.06	Destabilizing	0.450	Likely Benign	-3.48	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.4768	0.1738		1	1	0.4	-0.04
c.889A>G	K297E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while the SGM‑Consensus score is “Likely Pathogenic.” No tool in the dataset predicts a benign outcome; the only inconclusive result is FoldX, which is listed as “Uncertain” and is treated as unavailable. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, K297E is most likely pathogenic, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-10.143	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.99	Ambiguous	0.4	2.43	Destabilizing	2.21	Destabilizing	1.16	Destabilizing	0.507	Likely Pathogenic	-3.54	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.61	Pathogenic	0.02	Affected			0.4073	0.1547		0	1	0.4	0.94
c.891G>C	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.891G>T	K297N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K297N is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are therefore not considered evidence for or against pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Based on the preponderance of pathogenic predictions and the lack of benign consensus, K297N is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.422041	Structured	0.272593	Uncertain	0.880	0.285	0.375											-11.328	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.08	Ambiguous	0.1	1.60	Ambiguous	1.34	Ambiguous	1.15	Destabilizing	0.253	Likely Benign	-4.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.61	Pathogenic	0.01	Affected			0.3797	0.2265		1	0	0.4	-14.07
c.949C>G	L317V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L317V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely disagree: benign calls come from REVEL and AlphaMissense‑Optimized, while pathogenic calls are made by FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized predicting Benign, SGM‑Consensus predicting Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) yielding an Uncertain result. Overall, the majority of evidence points toward pathogenicity, with only two tools indicating benign. Because ClinVar contains no entry, there is no conflict with existing clinical interpretation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.106997	Structured	0.394031	Uncertain	0.874	0.240	0.125											-8.406	Likely Pathogenic	0.403	Ambiguous	Likely Benign	2.51	Destabilizing	0.1	0.97	Ambiguous	1.74	Ambiguous	1.12	Destabilizing	0.298	Likely Benign	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.74	Pathogenic	0.03	Affected			0.1518	0.2950		2	1	0.4	-14.03
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.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.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.997A>C	K333Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 K333Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, and SIFT, while those that agree on a pathogenic effect include PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Tools with inconclusive results are AlphaMissense‑Optimized, Foldetta, premPS, and Rosetta. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta as benign (combining FoldX‑MD and Rosetta outputs). Overall, the majority of evidence points toward a pathogenic classification, which does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-11.647	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous	0.00	Likely Benign	0.1	0.51	Ambiguous	0.26	Likely Benign	0.76	Ambiguous	0.444	Likely Benign	-3.11	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.08	Tolerated			0.4015	0.1219		1	1	0.4	-0.04
c.997A>G	K333E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K333E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and SIFT. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy assessments show 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 to a pathogenic impact for K333E. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-14.059	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	-0.06	Likely Benign	0.2	0.30	Likely Benign	0.12	Likely Benign	0.89	Ambiguous	0.488	Likely Benign	-3.21	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	1.91	Pathogenic	0.09	Tolerated			0.3429	0.1039		0	1	0.4	0.94
c.999A>C	K333N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K333N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from REVEL, FoldX, Rosetta, and SIFT, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The high‑accuracy subset yields contrasting results: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus also indicates Likely Pathogenic, while Foldetta (combining FoldX‑MD and Rosetta stability outputs) predicts benign. premPS is inconclusive. Overall, the majority of tools lean toward pathogenicity, and the high‑accuracy predictions are not uniformly supportive of benign status. Therefore, K333N is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-11.821	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	0.42	Likely Benign	0.36	Likely Benign	0.55	Ambiguous	0.359	Likely Benign	-4.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.13	Tolerated			0.3267	0.1315		1	0	0.4	-14.07
c.999A>T	K333N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K333N has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, and SIFT, whereas a larger group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The high‑accuracy methods give mixed results: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) reports a benign stability change. premPS is inconclusive and is treated as unavailable. Overall, the majority of evidence points to a pathogenic effect, and this assessment 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	C2	0.311707	Structured	0.330781	Uncertain	0.537	0.447	0.500											-11.821	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.30	Likely Benign	0.1	0.42	Likely Benign	0.36	Likely Benign	0.55	Ambiguous	0.366	Likely Benign	-4.03	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.91	Pathogenic	0.13	Tolerated			0.3267	0.1315		1	0	0.4	-14.07
c.101A>C	Y34S 2D AIThe SynGAP1 missense variant Y34S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Y34S, 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		0.529623	Disordered	0.435847	Uncertain	0.303	0.855	0.375											-0.994	Likely Benign	0.237	Likely Benign	Likely Benign										0.178	Likely Benign	-0.60	Neutral	0.824	Possibly Damaging	0.775	Possibly Damaging	4.19	Benign	0.00	Affected			0.4760	0.2884		-3	-2	0.5	-76.10
c.1025A>C	Y342S 2D 3DClick to see structure in 3D Viewer AISynGAP1 variant Y342S is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the majority of algorithms predict a pathogenic impact: FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and the Foldetta stability assessment (combining FoldX‑MD and Rosetta). Uncertain results come from premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy methods specifically give AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which contradicts the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.366687	Structured	0.408200	Uncertain	0.866	0.487	0.250					Uncertain		2				-7.996	In-Between	0.925	Likely Pathogenic	Ambiguous	3.03	Destabilizing	0.1	2.87	Destabilizing	2.95	Destabilizing	0.93	Ambiguous	0.407	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.75	Pathogenic	0.04	Affected	3.37	25	0.4617	0.2637		-3	-2	0.5	-76.10	200.1	77.8	0.0	0.0	-0.2	0.1								Potentially Pathogenic	The phenol ring of Tyr342, located at the end of an anti-parallel β sheet strand (res. Gly341-Pro349), faces outward in the C2 domain. In the WT simulations, the phenol ring of Tyr342 contributes to a triple tyrosine stack (Tyr342, Tyr328, and Tyr281) that links together three anti-parallel β sheet strands. Additionally, it shields Gly344 from the solvent, reducing its exposure and providing stability for the β-sandwich. This motif also contributes to a twist formation in the β sheet.In the variant simulations, the Ser342 side chain cannot participate in the stack formation. Instead, the hydroxyl group of the Ser342 side chain forms a hydrogen bond with the imidazole ring of His326 in a neighboring β strand (res. Ala322-Asp330). This disrupts the formation of a hydrogen bond between His326 and the carboxylate group of the Glu283 side chain from another β strand (res. Arg279-Cys285). Although these changes in surface interactions could weaken the characteristic twist that strengthens the β sheet fold, no major structural effects are observed in the variant simulations. The residue swap could also affect the SynGAP-membrane association, as the hydroxyl group of Ser342 could form hydrogen bonds with membrane-facing loop residues. However, this phenomenon cannot be addressed using solvent-only simulations.
c.1084T>G	W362G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W362G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD, so no population frequency data are available. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the single uncertain call (premPS) does not alter the overall consensus. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Thus, based on the collective predictions, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.430310	Uncertain	0.957	0.552	0.125											-14.242	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	4.22	Destabilizing	0.1	5.28	Destabilizing	4.75	Destabilizing	0.95	Ambiguous	0.707	Likely Pathogenic	-11.95	Deleterious	0.997	Probably Damaging	0.986	Probably Damaging	1.25	Pathogenic	0.00	Affected			0.4751	0.1281		-7	-2	0.5	-129.16
c.1088A>C	Y363S 2D AIThe SynGAP1 missense variant Y363S is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized is classified as “Uncertain”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the overwhelming majority of evidence points to a pathogenic effect for Y363S, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.321458	Structured	0.435392	Uncertain	0.954	0.586	0.125											-11.578	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	3.09	Destabilizing	0.6	3.92	Destabilizing	3.51	Destabilizing	1.45	Destabilizing	0.420	Likely Benign	-8.04	Deleterious	0.999	Probably Damaging	0.991	Probably Damaging	1.56	Pathogenic	0.01	Affected			0.5750	0.4208	Weaken	-3	-2	0.5	-76.10
c.116A>C	Y39S 2D AIThe SynGAP1 missense variant Y39S is not reported 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 results are unavailable. Overall, the majority of evidence points to a benign impact for Y39S, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.425610	Structured	0.432876	Uncertain	0.343	0.787	0.375											-1.634	Likely Benign	0.174	Likely Benign	Likely Benign										0.100	Likely Benign	-1.57	Neutral	0.824	Possibly Damaging	0.775	Possibly Damaging	4.02	Benign	0.00	Affected			0.4935	0.2649		-3	-2	0.5	-76.10
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.1250A>C	Y417S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y417S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to FATHMM, while all other evaluated algorithms—including SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) reports pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.346865	Uncertain	0.958	0.250	0.000											-14.339	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	4.36	Destabilizing	0.1	5.32	Destabilizing	4.84	Destabilizing	2.17	Destabilizing	0.593	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.98	Benign	0.00	Affected			0.4408	0.1961		-3	-2	0.5	-76.10
c.1268A>C	Y423S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y423S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic outcome. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Taken together, the preponderance of evidence points to a pathogenic effect for Y423S. 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	0.088832	Structured	0.421885	Uncertain	0.975	0.242	0.000											-10.847	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	4.28	Destabilizing	0.1	4.78	Destabilizing	4.53	Destabilizing	1.95	Destabilizing	0.345	Likely Benign	-7.39	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.09	Tolerated			0.3152	0.1259		-3	-2	0.5	-76.10
c.1283A>C	Y428S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y428S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM. All other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic effect. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.389652	Uncertain	0.965	0.292	0.000											-10.936	Likely Pathogenic	0.928	Likely Pathogenic	Ambiguous	3.00	Destabilizing	0.0	3.42	Destabilizing	3.21	Destabilizing	2.00	Destabilizing	0.505	Likely Pathogenic	-8.59	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.45	Benign	0.03	Affected			0.4623	0.2352		-3	-2	0.5	-76.10
c.130T>G	W44G 2D AIThe SynGAP1 missense variant W44G is not 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, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools predict pathogenicity (5) than benign (3), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.301917	Structured	0.431379	Uncertain	0.377	0.748	0.375											-4.658	Likely Benign	0.850	Likely Pathogenic	Ambiguous										0.323	Likely Benign	-4.80	Deleterious	0.659	Possibly Damaging	0.693	Possibly Damaging	3.16	Benign	0.00	Affected			0.4198	0.2164		-7	-2	0.5	-129.16
c.1490A>C	Y497S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y497S is not reported in ClinVar and is absent from gnomAD. Across the available in‑silico predictors, every tool examined (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized) classifies the change as pathogenic, leaving no benign predictions. High‑accuracy methods reinforce this assessment: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, indicates a destabilizing, pathogenic effect. No prediction or stability result is missing or inconclusive. Based on the unanimous pathogenic predictions and the absence of any ClinVar annotation, the variant is most likely pathogenic, with no contradictory ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.393608	Uncertain	0.950	0.181	0.000											-13.171	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	3.65	Destabilizing	0.1	4.68	Destabilizing	4.17	Destabilizing	2.22	Destabilizing	0.814	Likely Pathogenic	-8.82	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.64	Pathogenic	0.03	Affected			0.3770	0.1419		-3	-2	0.5	-76.10
c.1514A>C	Y505S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y505S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only FATHMM, whereas all other evaluated algorithms (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. No predictions are missing or inconclusive. Overall, the consensus of the available computational evidence indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no entry for Y505S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.292227	Uncertain	0.909	0.188	0.000											-14.053	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	3.49	Destabilizing	0.1	4.86	Destabilizing	4.18	Destabilizing	2.33	Destabilizing	0.559	Likely Pathogenic	-8.95	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.61	Benign	0.00	Affected			0.4056	0.1945		-3	-2	0.5	-76.10
c.1553A>C	Y518S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y518S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SIFT and FATHMM, whereas the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized is uncertain; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic effect. Taken together, the preponderance of evidence points to a pathogenic effect for Y518S, 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	0.139895	Structured	0.126970	Uncertain	0.897	0.321	0.000											-12.453	Likely Pathogenic	0.912	Likely Pathogenic	Ambiguous	2.76	Destabilizing	0.8	2.45	Destabilizing	2.61	Destabilizing	1.61	Destabilizing	0.551	Likely Pathogenic	-8.38	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.43	Benign	0.06	Tolerated			0.3948	0.1059		-3	-2	0.5	-76.10
c.1714T>G	W572G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W572G is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a pathogenic outcome. No tool in the dataset predicts a benign effect. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. Based on the uniform pathogenic predictions from both general and high‑accuracy tools, the variant is most likely pathogenic, a conclusion that contradicts its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.150080	Structured	0.039626	Uncertain	0.935	0.256	0.000					Uncertain		1				-17.692	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	6.57	Destabilizing	0.2	7.57	Destabilizing	7.07	Destabilizing	1.83	Destabilizing	0.900	Likely Pathogenic	-11.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.24	Pathogenic	0.00	Affected	3.37	35	0.4128	0.1285		-7	-2	0.5	-129.16	195.2	127.9	0.0	0.0	-1.0	0.0							X	Potentially Pathogenic	The introduced residue Gly572, located in an α-helix (res. Arg563-Glu578), is considerably smaller than the tryptophan it replaced. The indole ring of the Trp572 side chain lies in a hydrophobic inter-helix space, where it makes extensive hydrophobic interactions with nearby residues such as Met470, Phe569, Leu588, and Ile589. In the variant simulations, all these favorable packing interactions are completely removed, as the introduced residue Gly572 essentially lacks a side chain altogether. Although not observed in the simulations, the residue swap could also weaken the integrity of the helix (res. Arg563-Glu578), as glycine is known as an “α-helix breaker.” Overall, the residue swap is highly likely to cause critical protein folding problems that are underestimated based on the effects seen in the variant simulations.
c.1841A>C	Y614S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Y614S is not reported in ClinVar and is present in gnomAD (ID 6‑33440893‑A‑C). Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, whereas the majority of algorithms—AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 (HumDiv and HumVar), premPS, Rosetta, Foldetta, and the SGM Consensus—indicate pathogenicity; FoldX remains uncertain. High‑accuracy assessments reinforce the pathogenic signal: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Overall, the preponderance of evidence points to a pathogenic classification, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.314870	Structured	0.182134	Uncertain	0.852	0.254	0.000								6-33440893-A-C	1	6.20e-7	-12.709	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	1.74	Ambiguous	0.4	3.25	Destabilizing	2.50	Destabilizing	2.05	Destabilizing	0.482	Likely Benign	-8.83	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.48	Benign	0.09	Tolerated	3.37	35	0.4155	0.1220		-2	-3	0.5	-76.10
c.1969T>G	W657G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W657G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM. In contrast, the majority of other in silico predictors (AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FoldX, Rosetta, premPS, Foldetta) all classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No predictions are missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.030611	Structured	0.208729	Uncertain	0.941	0.245	0.000											-12.559	Likely Pathogenic	0.968	Likely Pathogenic	Likely Pathogenic	3.04	Destabilizing	0.2	2.80	Destabilizing	2.92	Destabilizing	1.28	Destabilizing	0.389	Likely Benign	-11.16	Deleterious	0.999	Probably Damaging	0.941	Probably Damaging	3.46	Benign	0.15	Tolerated			0.4470	0.0885		-7	-2	0.5	-129.16
c.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.2045A>C	Y682S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y682S has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are SIFT and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Y682S, 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	0.206376	Structured	0.141467	Uncertain	0.758	0.328	0.000											-11.058	Likely Pathogenic	0.894	Likely Pathogenic	Ambiguous	2.12	Destabilizing	0.1	1.12	Ambiguous	1.62	Ambiguous	0.88	Ambiguous	0.552	Likely Pathogenic	-8.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.42	Benign	0.12	Tolerated			0.4487	0.2343		-3	-2	0.5	-76.10
c.2089T>G	W697G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 W697G missense change 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, SIFT, FATHMM, and AlphaMissense‑Optimized. In contrast, a majority of tools predict a pathogenic outcome: FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar). AlphaMissense‑Default and ESM1b are uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it receives one benign, one pathogenic, and two uncertain calls. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus remains unavailable. Overall, the preponderance of evidence from multiple independent pathogenicity predictors and the protein‑stability assessment by Foldetta indicates that W697G is most likely pathogenic. 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.		GAP	0.175930	Structured	0.400169	Uncertain	0.945	0.297	0.000											-7.429	In-Between	0.480	Ambiguous	Likely Benign	2.57	Destabilizing	0.1	2.38	Destabilizing	2.48	Destabilizing	1.21	Destabilizing	0.485	Likely Benign	-8.93	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.44	Benign	0.06	Tolerated			0.3965	0.1482		-7	-2	0.5	-129.16
c.2273A>C	Y758S 2D AIThe SynGAP1 missense variant Y758S is reported in gnomAD (variant ID 6‑33441738‑A‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict it to be pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority‑vote) is benign. 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 benign impact, and this assessment 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		0.517562	Disordered	0.856063	Binding	0.289	0.871	0.375								6-33441738-A-C	1	6.20e-7	-1.912	Likely Benign	0.215	Likely Benign	Likely Benign										0.110	Likely Benign	-0.54	Neutral	0.912	Possibly Damaging	0.629	Possibly Damaging	2.75	Benign	0.06	Tolerated	3.99	5	0.5377	0.1663	Weaken	-2	-3	0.5	-76.10
c.2420A>C	Y807S 2D AIThe SynGAP1 Y807S variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on benign impact include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b, while those that predict pathogenicity are PROVEAN, SIFT, and FATHMM. AlphaMissense‑Default is uncertain, whereas AlphaMissense‑Optimized predicts benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, leans toward pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of conventional tools (four benign vs. three pathogenic) suggest a benign effect, and the high‑accuracy AlphaMissense‑Optimized also predicts benign, while the SGM Consensus predicts pathogenic. Based on the balance of evidence, the variant is most likely benign, and this assessment does not contradict the lack of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.699094	Disordered	0.853760	Binding	0.336	0.901	0.500											-5.517	Likely Benign	0.384	Ambiguous	Likely Benign										0.093	Likely Benign	-3.90	Deleterious	0.136	Benign	0.067	Benign	2.44	Pathogenic	0.01	Affected			0.4561	0.1884		-3	-2	0.5	-76.10
c.2459A>C	Y820S 2D AIThe SynGAP1 missense variant Y820S is not 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 AlphaMissense‑Default; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign (2 benign vs. 1 pathogenic). 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 does not contradict any ClinVar annotation because no ClinVar entry exists for Y820S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.733139	Disordered	0.695550	Binding	0.293	0.883	0.625											-7.094	In-Between	0.723	Likely Pathogenic	Likely Benign										0.101	Likely Benign	-1.79	Neutral	0.999	Probably Damaging	0.951	Probably Damaging	2.80	Benign	0.22	Tolerated			0.5166	0.2291	Weaken	-3	-2	0.5	-76.10
c.2945A>C	Y982S 2D AIThe SynGAP1 missense variant Y982S 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. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. High‑accuracy assessments show the SGM‑Consensus as Likely Benign, AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion 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		0.707965	Disordered	0.966717	Binding	0.272	0.895	0.625											-2.919	Likely Benign	0.841	Likely Pathogenic	Ambiguous										0.131	Likely Benign	-1.04	Neutral	0.965	Probably Damaging	0.783	Possibly Damaging	3.89	Benign	0.00	Affected			0.4556	0.1883		-3	-2	0.5	-76.10
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.3017A>C	Y1006S 2D AIThe SynGAP1 missense variant Y1006S has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) 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 majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for Y1006S. 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											-2.522	Likely Benign	0.582	Likely Pathogenic	Likely Benign										0.170	Likely Benign	-0.58	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.83	Benign	0.90	Tolerated			0.4426	0.2274		-3	-2	0.5	-76.10
c.3296A>C	Y1099S 2D AIThe SynGAP1 missense variant Y1099S 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 from 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		0.885302	Disordered	0.974267	Binding	0.400	0.862	1.000											-1.775	Likely Benign	0.139	Likely Benign	Likely Benign										0.156	Likely Benign	-0.23	Neutral	0.149	Benign	0.026	Benign	2.90	Benign	0.62	Tolerated			0.4564	0.2298		-3	-2	0.5	-76.10
c.3469T>G	W1157G 2D AIThe SynGAP1 missense variant W1157G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate pathogenicity. Only ESM1b predicts a benign outcome, representing the sole disagreement. High‑accuracy assessments further support a harmful impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus labels it as Likely Pathogenic. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a pathogenic effect, and this conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with ClinVar status. Thus, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.694846	Disordered	0.877471	Binding	0.364	0.861	0.375											-2.328	Likely Benign	0.999	Likely Pathogenic	Likely Pathogenic										0.558	Likely Pathogenic	-9.50	Deleterious	0.997	Probably Damaging	0.995	Probably Damaging	1.06	Pathogenic	0.00	Affected			0.4631	0.2065		-7	-2	0.5	-129.16
c.347A>C	Y116S 2D AIThe SynGAP1 missense variant Y116S 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 view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions strongly suggests that Y116S 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		0.661982	Disordered	0.670235	Binding	0.381	0.878	0.625											-0.249	Likely Benign	0.269	Likely Benign	Likely Benign										0.178	Likely Benign	-0.05	Neutral	0.033	Benign	0.013	Benign	4.31	Benign	0.58	Tolerated			0.5111	0.1694	Weaken	-3	-2	0.5	-76.10
c.3533A>C	Y1178S 2D AIThe SynGAP1 missense variant Y1178S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.541878	Disordered	0.568433	Binding	0.554	0.688	0.250											-1.440	Likely Benign	0.771	Likely Pathogenic	Likely Benign										0.329	Likely Benign	-1.53	Neutral	0.983	Probably Damaging	0.769	Possibly Damaging	5.57	Benign	0.33	Tolerated			0.5225	0.1626	Weaken	-3	-2	0.5	-76.10
c.3548A>C	Y1183S 2D AIThe SynGAP1 missense variant Y1183S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, PROVEAN, SIFT, ESM1b, FATHMM) and pathogenic predictions (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, AlphaMissense‑Optimized). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the balance of evidence leans toward a benign impact for Y1183S, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.566480	Disordered	0.527818	Binding	0.523	0.652	0.500											-2.514	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.164	Likely Benign	-1.57	Neutral	0.951	Possibly Damaging	0.619	Possibly Damaging	2.86	Benign	0.51	Tolerated			0.5346	0.1096	Weaken	-3	-2	0.5	-76.10
c.3593A>C	Y1198S 2D AIThe SynGAP1 missense variant Y1198S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. 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) 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. 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	0.626927	Disordered	0.439379	Uncertain	0.853	0.593	0.250											-13.252	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic										0.398	Likely Benign	-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.38	Tolerated			0.4901	0.1043		-3	-2	0.5	-76.10
c.3656A>C	Y1219S 2D AIThe SynGAP1 missense variant Y1219S is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.613573	Disordered	0.474748	Uncertain	0.855	0.557	0.375											-11.227	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.424	Likely Benign	-6.05	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.18	Pathogenic	0.00	Affected			0.5047	0.1403	Weaken	-3	-2	0.5	-76.10
c.3710A>C	Y1237S 2D AIThe SynGAP1 missense variant Y1237S is 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 predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—classify the variant as pathogenic. The SGM‑Consensus, a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, therefore also predicts pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) is pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of any benign consensus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.653063	Disordered	0.563444	Binding	0.842	0.535	0.125											-10.349	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic										0.463	Likely Benign	-7.21	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.45	Pathogenic	0.00	Affected			0.5127	0.0891	Weaken	-3	-2	0.5	-76.10
c.3943T>G	W1315G 2D AIThe SynGAP1 missense variant W1315G is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports 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 supports a benign classification, 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		0.885302	Disordered	0.973142	Binding	0.403	0.889	0.750											0.687	Likely Benign	0.193	Likely Benign	Likely Benign										0.113	Likely Benign	-1.36	Neutral	0.208	Benign	0.077	Benign	4.21	Benign	0.12	Tolerated			0.4126	0.1745		-7	-2	0.5	-129.16
c.53A>C	Y18S 2D AIThe SynGAP1 missense variant Y18S is reported in gnomAD (ID 6‑33420317‑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 classify the change as benign, while only SIFT predicts it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a benign impact for Y18S. This conclusion is consistent with the absence of a pathogenic ClinVar 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		0.483068	Structured	0.446314	Uncertain	0.345	0.908	0.375								6-33420317-A-C			-1.061	Likely Benign	0.280	Likely Benign	Likely Benign										0.124	Likely Benign	-0.50	Neutral	0.389	Benign	0.036	Benign	4.09	Benign	0.00	Affected	4.32	1	0.4961	0.2640		-2	-3	0.5	-76.10
c.724T>G	W242G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W242G is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD, so no population frequency data are available. Prediction tools that assess pathogenicity all converge on a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity, while the single uncertain call from premPS is treated as unavailable. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.328603	Structured	0.352582	Uncertain	0.847	0.341	0.000											-14.319	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	2.70	Destabilizing	0.3	2.48	Destabilizing	2.59	Destabilizing	0.83	Ambiguous	0.883	Likely Pathogenic	-11.80	Deleterious	0.900	Possibly Damaging	0.452	Possibly Damaging	1.52	Pathogenic	0.00	Affected			0.4378	0.1851		-7	-2	0.5	-129.16
c.799T>G	W267G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W267G is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy methods corroborate this: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Thus, the variant is most likely pathogenic, with no contradiction to its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.216401	Structured	0.298060	Uncertain	0.943	0.274	0.000											-15.020	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	4.40	Destabilizing	0.2	3.99	Destabilizing	4.20	Destabilizing	1.20	Destabilizing	0.678	Likely Pathogenic	-11.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.96	Pathogenic	0.03	Affected			0.4049	0.1481		-7	-2	0.5	-129.16
c.839A>C	Y280S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y280S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions are absent; all evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) classify the substitution as pathogenic. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a likely pathogenic verdict, and Foldetta (integrating FoldX‑MD and Rosetta outputs) also reports pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.321243	Uncertain	0.917	0.248	0.125											-13.491	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	4.63	Destabilizing	0.3	4.80	Destabilizing	4.72	Destabilizing	2.03	Destabilizing	0.635	Likely Pathogenic	-8.27	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.00	Pathogenic	0.05	Affected			0.3993	0.1227		-3	-2	0.5	-76.10
c.842A>C	Y281S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y281S is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: the single benign prediction comes from SIFT, while the remaining tools—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus—predict pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is Pathogenic. With the overwhelming majority of evidence indicating pathogenicity and no ClinVar annotation to contradict this, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.337647	Uncertain	0.927	0.254	0.000											-9.541	Likely Pathogenic	0.847	Likely Pathogenic	Ambiguous	3.24	Destabilizing	0.3	3.02	Destabilizing	3.13	Destabilizing	1.59	Destabilizing	0.642	Likely Pathogenic	-5.68	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.02	Pathogenic	0.12	Tolerated			0.4203	0.2543		-3	-2	0.5	-76.10
c.872A>C	Y291S 2D AIThe SynGAP1 missense variant Y291S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). All evaluated in silico predictors classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions or stability results are missing or inconclusive. Based on the unanimous pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.173081	Structured	0.383842	Uncertain	0.912	0.251	0.000											-11.928	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	3.47	Destabilizing	0.8	4.47	Destabilizing	3.97	Destabilizing	2.01	Destabilizing	0.588	Likely Pathogenic	-7.31	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.83	Pathogenic	0.02	Affected			0.4850	0.2079		-3	-2	0.5	-76.10
c.922T>G	W308G 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant W308G is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity all converge on a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. No tool predicts a benign effect, so the benign group is empty. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the unanimous predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which simply lacks an entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.333942	Uncertain	0.907	0.314	0.125											-16.271	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	6.88	Destabilizing	0.2	5.07	Destabilizing	5.98	Destabilizing	1.97	Destabilizing	0.860	Likely Pathogenic	-11.95	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	0.48	Pathogenic	0.00	Affected			0.4884	0.1644		-7	-2	0.5	-129.16
c.983A>C	Y328S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Y328S is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity uniformly classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a pathogenic impact on protein stability. Based on the unanimous computational evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.411940	Structured	0.392519	Uncertain	0.916	0.497	0.000											-12.358	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	3.13	Destabilizing	0.1	4.55	Destabilizing	3.84	Destabilizing	1.80	Destabilizing	0.586	Likely Pathogenic	-8.01	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.54	Pathogenic	0.01	Affected			0.4924	0.2449		-3	-2	0.5	-76.10
c.1496G>A	R499K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R499K is not reported 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive, providing no evidence for either direction. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also yields a benign prediction; Foldetta remains uncertain. Overall, the preponderance of evidence points to a benign effect for R499K, and this conclusion is consistent with the absence of any ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.071867	Structured	0.386723	Uncertain	0.899	0.146	0.000											4.366	Likely Benign	0.091	Likely Benign	Likely Benign	1.37	Ambiguous	0.1	0.53	Ambiguous	0.95	Ambiguous	-0.77	Ambiguous	0.248	Likely Benign	1.94	Neutral	0.001	Benign	0.008	Benign	-1.03	Pathogenic	1.00	Tolerated			0.3531	0.1881		3	2	0.6	-28.01
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.1760G>A	R587K 2D 3DClick to see structure in 3D Viewer AISynGAP1 R587K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions from SIFT and AlphaMissense‑Optimized, and pathogenic predictions from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain results. 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 likely pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus prediction but contradicts the benign calls from SIFT and AlphaMissense‑Optimized. 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	GAP	0.054297	Structured	0.077330	Uncertain	0.862	0.216	0.000											-10.220	Likely Pathogenic	0.433	Ambiguous	Likely Benign	0.63	Ambiguous	0.1	1.14	Ambiguous	0.89	Ambiguous	0.88	Ambiguous	0.539	Likely Pathogenic	-2.55	Deleterious	0.967	Probably Damaging	0.955	Probably Damaging	-1.16	Pathogenic	0.07	Tolerated			0.5313	0.3897	Weaken	3	2	0.6	-28.01
c.2177G>A	R726K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R726K is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only two tools—polyPhen‑2 HumDiv and polyPhen‑2 HumVar—predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. No prediction or folding‑stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.449098	Uncertain	0.888	0.513	0.625											-5.344	Likely Benign	0.231	Likely Benign	Likely Benign	0.28	Likely Benign	0.0	-0.02	Likely Benign	0.13	Likely Benign	0.20	Likely Benign	0.154	Likely Benign	-0.63	Neutral	0.990	Probably Damaging	0.998	Probably Damaging	2.67	Benign	0.16	Tolerated			0.4920	0.4042		3	2	0.6	-28.01
c.218G>A	R73K 2D AIThe SynGAP1 missense variant R73K is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33425826‑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 score (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized returns a benign prediction, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.453164	Uncertain	0.332	0.826	0.375					Uncertain		1	6-33425826-G-A	2	1.24e-6	-4.033	Likely Benign	0.151	Likely Benign	Likely Benign										0.077	Likely Benign	-0.46	Neutral	0.053	Benign	0.007	Benign	4.14	Benign	0.00	Affected	4.32	1	0.5194	0.4428	Weaken	2	3	0.6	-28.01
c.2195G>A	R732K 2D AIThe SynGAP1 missense variant R732K is listed in ClinVar (ID 537019.0) with an “Uncertain” clinical significance and is present in gnomAD (6‑33441660‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, and this consensus does not conflict with the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.846163	Disordered	0.412403	Uncertain	0.427	0.673	0.750					Conflicting		2	6-33441660-G-A	4	2.48e-6	-5.278	Likely Benign	0.240	Likely Benign	Likely Benign										0.045	Likely Benign	-0.82	Neutral	0.973	Probably Damaging	0.943	Probably Damaging	2.69	Benign	0.21	Tolerated	3.59	7	0.4194	0.3923		3	2	0.6	-28.01
c.248G>A	R83K 2D AIThe SynGAP1 missense variant R83K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” while AlphaMissense‑Optimized is “Uncertain.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, 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		0.637480	Disordered	0.522784	Binding	0.275	0.895	0.250											-3.480	Likely Benign	0.930	Likely Pathogenic	Ambiguous										0.101	Likely Benign	-0.87	Neutral	0.643	Possibly Damaging	0.364	Benign	3.28	Benign	0.00	Affected			0.4715	0.3091		3	2	0.6	-28.01
c.3128G>A	R1043K 2D AIThe SynGAP1 missense variant R1043K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar or gnomAD entries—there is no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978672	Disordered	0.954069	Binding	0.299	0.853	0.625											-4.038	Likely Benign	0.162	Likely Benign	Likely Benign										0.376	Likely Benign	-1.41	Neutral	0.069	Benign	0.033	Benign	5.39	Benign	0.00	Affected			0.5141	0.4070	Weaken	3	2	0.6	-28.01
c.317G>A	R106K 2D AIThe SynGAP1 missense variant R106K is not reported 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 R106K, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875											-4.312	Likely Benign	0.513	Ambiguous	Likely Benign										0.150	Likely Benign	-1.25	Neutral	0.004	Benign	0.001	Benign	3.82	Benign	0.00	Affected			0.5602	0.4129	Weaken	3	2	0.6	-28.01
c.3209G>A	R1070K 2D AIThe SynGAP1 missense variant R1070K is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All evaluated in‑silico predictors agree on a benign effect: 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.” High‑accuracy tools reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta results are unavailable. Based on the unanimous benign 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		0.930790	Disordered	0.982693	Binding	0.297	0.906	0.875					Conflicting		2				-5.093	Likely Benign	0.326	Likely Benign	Likely Benign										0.104	Likely Benign	-1.42	Neutral	0.049	Benign	0.048	Benign	3.86	Benign	0.09	Tolerated	3.77	5	0.4997	0.4867		3	2	0.6	-28.01
c.320G>A	R107K 2D AIThe SynGAP1 missense variant R107K 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, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default, while 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 R107K, 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		0.666105	Disordered	0.663448	Binding	0.331	0.863	0.875											-3.941	Likely Benign	0.758	Likely Pathogenic	Likely Benign										0.153	Likely Benign	-1.33	Neutral	0.004	Benign	0.001	Benign	3.07	Benign	0.00	Affected			0.5618	0.4185	Weaken	3	2	0.6	-28.01
c.3581G>A	R1194K 2D AIThe SynGAP1 missense variant R1194K is catalogued in gnomAD (6‑33444616‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by both polyPhen‑2 HumDiv and HumVar. AlphaMissense‑Default is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence is consistent with benign impact: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus also indicates a likely benign outcome. In the absence of any pathogenic signal from these robust predictors and with no ClinVar classification to contradict, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375								6-33444616-G-A	1	6.21e-7	-2.501	Likely Benign	0.486	Ambiguous	Likely Benign										0.380	Likely Benign	-0.97	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	5.56	Benign	0.14	Tolerated	3.77	5	0.4637	0.3297		2	3	0.6	-28.01
c.3665G>A	R1222K 2D AIThe SynGAP1 missense variant R1222K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized classifies the change as benign, whereas the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus designation but contradicts the benign calls from several other predictors. Thus, based on the current computational predictions, the variant is most likely pathogenic, and this assessment aligns with the lack of ClinVar reporting rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.703578	Disordered	0.423869	Uncertain	0.895	0.541	0.250											-9.148	Likely Pathogenic	0.689	Likely Pathogenic	Likely Benign										0.249	Likely Benign	-2.05	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	1.57	Pathogenic	0.54	Tolerated			0.3714	0.2611		3	2	0.6	-28.01
c.3740G>A	R1247K 2D AIThe SynGAP1 missense variant R1247K is reported in gnomAD (6-33446732‑G‑A) and has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are SIFT and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this assessment. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.736850	Disordered	0.374141	Uncertain	0.875	0.557	0.625								6-33446732-G-A	4	2.48e-6	-4.713	Likely Benign	0.179	Likely Benign	Likely Benign										0.082	Likely Benign	-2.39	Neutral	0.122	Benign	0.064	Benign	1.80	Pathogenic	0.00	Affected	3.77	5	0.3428	0.2175		2	3	0.6	-28.01
c.3746G>A	R1249K 2D AIThe SynGAP1 missense variant R1249K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports it as likely benign. In contrast, SIFT and FATHMM predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; no Foldetta stability data are available, so it does not influence the overall assessment. Overall, the preponderance of evidence points to a benign effect for R1249K, 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	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875											-5.782	Likely Benign	0.205	Likely Benign	Likely Benign										0.064	Likely Benign	-1.99	Neutral	0.219	Benign	0.191	Benign	1.80	Pathogenic	0.00	Affected			0.3343	0.2413		3	2	0.6	-28.01
c.3794G>A	R1265K 2D AIThe SynGAP1 missense variant R1265K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields a 2‑to‑2 split. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.414856	Structured	0.782497	Binding	0.887	0.592	0.000											-5.223	Likely Benign	0.951	Likely Pathogenic	Ambiguous										0.344	Likely Benign	-2.49	Neutral	0.992	Probably Damaging	0.987	Probably Damaging	2.38	Pathogenic	0.00	Affected			0.4829	0.3632		3	2	0.6	-28.01
c.3869G>A	R1290K 2D AIThe SynGAP1 missense variant R1290K is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective predictions strongly suggest that the variant is most likely benign, and this conclusion is consistent with the lack of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.844138	Binding	0.567	0.795	0.625											-3.749	Likely Benign	0.145	Likely Benign	Likely Benign										0.037	Likely Benign	0.52	Neutral	0.004	Benign	0.006	Benign	3.09	Benign	1.00	Tolerated			0.3342	0.3113		3	2	0.6	-28.01
c.3890G>A	R1297K 2D AIThe SynGAP1 missense variant R1297K is catalogued in gnomAD (ID 6‑33451764‑G‑A) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as tolerated or benign. Grouping by consensus, all listed predictors fall into the benign category, with no tool reporting a pathogenic outcome. 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 classification. Foldetta stability analysis is unavailable for this variant. Consequently, the aggregate evidence strongly supports a benign interpretation, and this assessment does not conflict with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.895222	Binding	0.511	0.817	0.625								6-33451764-G-A	1	6.20e-7	-3.780	Likely Benign	0.114	Likely Benign	Likely Benign										0.074	Likely Benign	0.55	Neutral	0.000	Benign	0.004	Benign	2.80	Benign	1.00	Tolerated	3.77	5	0.4109	0.2801		2	3	0.6	-28.01
c.65G>A	R22K 2D AIThe SynGAP1 missense variant R22K is reported in gnomAD (variant ID 6‑33420329‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for R22K, 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		0.538167	Disordered	0.441505	Uncertain	0.377	0.891	0.500								6-33420329-G-A			-4.736	Likely Benign	0.268	Likely Benign	Likely Benign										0.032	Likely Benign	-0.12	Neutral	0.140	Benign	0.067	Benign	4.27	Benign	0.00	Affected	4.32	1	0.6413	0.5384	Strenghten	2	3	0.6	-28.01
c.716G>A	R239K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R239K missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect are polyPhen‑2 HumVar and FATHMM, while the majority of other in silico predictors (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. High‑accuracy assessments show that AlphaMissense‑Optimized is uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is uncertain. Because uncertain or unavailable results are not taken as evidence for or against pathogenicity, the overall evidence still leans toward a deleterious effect. Consequently, 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	PH	0.170161	Structured	0.336504	Uncertain	0.854	0.319	0.000											-12.492	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	1.93	Ambiguous	0.2	1.62	Ambiguous	1.78	Ambiguous	1.41	Destabilizing	0.719	Likely Pathogenic	-2.52	Deleterious	0.882	Possibly Damaging	0.428	Benign	5.78	Benign	0.03	Affected			0.5222	0.4000	Weaken	3	2	0.6	-28.01
c.8G>A	R3K 2D AIThe SynGAP1 missense variant R3K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect. 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		0.538167	Disordered	0.550331	Binding	0.358	0.920	0.875											-4.378	Likely Benign	0.254	Likely Benign	Likely Benign										0.062	Likely Benign	-0.45	Neutral	0.001	Benign	0.000	Benign	4.09	Benign	0.00	Affected			0.5842	0.4564	Weaken	3	2	0.6	-28.01
c.1246C>A	L416I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L416I missense variant 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, premPS, PROVEAN, SIFT, and FATHMM. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that remain inconclusive are FoldX, Rosetta, AlphaMissense‑Default, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is uncertain. Overall, the preponderance of evidence points to a benign effect. This conclusion is not contradicted by any ClinVar annotation, as the variant has no existing ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000											-8.613	Likely Pathogenic	0.396	Ambiguous	Likely Benign	0.57	Ambiguous	0.0	0.69	Ambiguous	0.63	Ambiguous	0.50	Likely Benign	0.127	Likely Benign	-1.28	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.38	Benign	0.37	Tolerated			0.1073	0.3480		2	2	0.7	0.00
c.1351C>A	L451I 2D AIThe SynGAP1 L451I missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain results come from FoldX, Rosetta, premPS, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta is also inconclusive. Overall, the majority of available predictions (five pathogenic versus four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar record. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.281712	Structured	0.314017	Uncertain	0.978	0.232	0.000											-11.046	Likely Pathogenic	0.658	Likely Pathogenic	Likely Benign	1.43	Ambiguous	0.8	0.70	Ambiguous	1.07	Ambiguous	0.94	Ambiguous	0.284	Likely Benign	-1.94	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	2.75	Benign	0.02	Affected			0.0681	0.2958		2	2	0.7	0.00
c.1393C>A	L465I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L465I missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score classifies the variant as benign, whereas the Foldetta stability assessment is uncertain. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive due to a 2‑to‑2 split. Overall, the evidence is mixed; the balance of predictions leans toward a benign interpretation, and this does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000											-9.672	Likely Pathogenic	0.770	Likely Pathogenic	Likely Benign	1.21	Ambiguous	0.1	1.27	Ambiguous	1.24	Ambiguous	0.78	Ambiguous	0.258	Likely Benign	-1.99	Neutral	0.998	Probably Damaging	0.997	Probably Damaging	2.54	Benign	0.08	Tolerated			0.0967	0.3539		2	2	0.7	0.00
c.1444C>A	L482I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from PROVEAN and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (REVEL, polyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) indicate pathogenicity. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments give a consistent picture: AlphaMissense‑Optimized predicts a benign effect, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain outcome. Overall, the preponderance of pathogenic predictions suggests that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000											-11.116	Likely Pathogenic	0.760	Likely Pathogenic	Likely Benign	1.29	Ambiguous	0.1	1.90	Ambiguous	1.60	Ambiguous	0.71	Ambiguous	0.600	Likely Pathogenic	-1.97	Neutral	0.994	Probably Damaging	0.994	Probably Damaging	-1.31	Pathogenic	0.05	Affected			0.0677	0.2368		2	2	0.7	0.00
c.1465C>A	L489I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into three groups: benign predictions come from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; the remaining methods (FoldX, Rosetta, Foldetta, premPS, ESM1b, AlphaMissense‑Default) yield uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is indeterminate due to a tie between pathogenic and benign signals, and Foldetta reports an uncertain stability change. 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.		GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125											-7.333	In-Between	0.342	Ambiguous	Likely Benign	1.01	Ambiguous	0.0	0.52	Ambiguous	0.77	Ambiguous	0.90	Ambiguous	0.490	Likely Benign	-1.55	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	-1.42	Pathogenic	0.21	Tolerated			0.1069	0.4080		2	2	0.7	0.00
c.1516C>A	L506I 2D AIThe SynGAP1 missense variant L506I is not reported in ClinVar and is absent from gnomAD. Consensus from standard in‑silico predictors shows a split: benign calls come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. Uncertain results are reported by FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments give a pathogenic verdict from Foldetta (a combined FoldX‑MD/Rosetta stability analysis) and from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). AlphaMissense‑Optimized, however, predicts benign. Overall, the majority of reliable tools and the high‑accuracy methods favor a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000											-10.386	Likely Pathogenic	0.501	Ambiguous	Likely Benign	1.73	Ambiguous	1.0	2.85	Destabilizing	2.29	Destabilizing	0.98	Ambiguous	0.365	Likely Benign	-1.99	Neutral	0.998	Probably Damaging	0.997	Probably Damaging	1.65	Pathogenic	0.01	Affected			0.0745	0.2033		2	2	0.7	0.00
c.169C>A	L57I 2D AIThe SynGAP1 missense variant L57I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for the L57I variant, 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		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000											-3.681	Likely Benign	0.275	Likely Benign	Likely Benign										0.024	Likely Benign	-0.07	Neutral	0.458	Possibly Damaging	0.745	Possibly Damaging	4.10	Benign	0.00	Affected			0.0973	0.4106		2	2	0.7	0.00
c.1762C>A	L588I 2D AISynGAP1 missense variant L588I has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify the variant as benign include PROVEAN. Those that predict pathogenicity are SGM‑Consensus, REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results come from Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence supports a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000											-12.454	Likely Pathogenic	0.874	Likely Pathogenic	Ambiguous	2.54	Destabilizing	1.2	1.80	Ambiguous	2.17	Destabilizing	0.88	Ambiguous	0.607	Likely Pathogenic	-1.99	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	-1.27	Pathogenic	0.04	Affected			0.0949	0.2433		2	2	0.7	0.00
c.1777C>A	L593I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L593I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Predictions that are uncertain are Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign effect. The variant’s predicted benign status does not contradict its ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009728	Structured	0.110534	Uncertain	0.941	0.151	0.000											-8.617	Likely Pathogenic	0.448	Ambiguous	Likely Benign	2.16	Destabilizing	0.3	0.76	Ambiguous	1.46	Ambiguous	0.39	Likely Benign	0.169	Likely Benign	-1.59	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.14	Benign	0.17	Tolerated			0.1071	0.3582		2	2	0.7	0.00
c.1792C>A	L598I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L598I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar) and ESM1b. The remaining tools (FoldX, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign impact. This conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000											-9.396	Likely Pathogenic	0.512	Ambiguous	Likely Benign	0.80	Ambiguous	0.0	0.38	Likely Benign	0.59	Ambiguous	0.78	Ambiguous	0.246	Likely Benign	-1.96	Neutral	0.988	Probably Damaging	0.910	Probably Damaging	3.47	Benign	0.10	Tolerated			0.0792	0.2000		2	2	0.7	0.00
c.1819C>A	L607I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L607I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from SGM‑Consensus, REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default, while benign calls are made by PROVEAN and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Stability predictions from FoldX, Rosetta, and premPS are inconclusive. Overall, the preponderance of evidence points to a pathogenic effect for L607I. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.194229	Uncertain	0.869	0.250	0.000											-12.061	Likely Pathogenic	0.644	Likely Pathogenic	Likely Benign	0.63	Ambiguous	0.1	1.25	Ambiguous	0.94	Ambiguous	0.82	Ambiguous	0.727	Likely Pathogenic	-1.99	Neutral	0.992	Probably Damaging	0.997	Probably Damaging	-1.54	Pathogenic	0.01	Affected			0.1079	0.3767		2	2	0.7	0.00
c.1828C>A	L610I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610I is listed in gnomAD (ID 6‑33440880‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar) and FATHMM. Four tools are uncertain (FoldX, Foldetta, premPS, AlphaMissense‑Default). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores benign, the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, whereas Foldetta’s stability estimate is unavailable. Overall, the balance of evidence points to a benign effect for L610I, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000								6-33440880-C-A	1	6.19e-7	-6.362	Likely Benign	0.389	Ambiguous	Likely Benign	1.50	Ambiguous	0.2	0.18	Likely Benign	0.84	Ambiguous	0.76	Ambiguous	0.544	Likely Pathogenic	-1.86	Neutral	0.992	Probably Damaging	0.997	Probably Damaging	-1.34	Pathogenic	0.15	Tolerated	3.37	35	0.0999	0.3219		2	2	0.7	0.00
c.1867C>A	L623I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come only from REVEL and PROVEAN, while pathogenic calls are made by FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Uncertain results are reported by Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments reinforce the pathogenic prediction: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenicity. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000											-11.952	Likely Pathogenic	0.911	Likely Pathogenic	Ambiguous	3.15	Destabilizing	0.5	1.90	Ambiguous	2.53	Destabilizing	1.13	Destabilizing	0.398	Likely Benign	-1.99	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.63	Pathogenic	0.02	Affected			0.1109	0.3767		2	2	0.7	0.00
c.1873C>A	L625I 2D AIThe SynGAP1 missense variant L625I is not 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 a majority of tools (premPS, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. Tools with uncertain or inconclusive results—FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized—are treated as unavailable. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta is uncertain. Consequently, the overall evidence leans toward pathogenicity, 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.		GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000											-11.713	Likely Pathogenic	0.866	Likely Pathogenic	Ambiguous	0.75	Ambiguous	0.6	0.72	Ambiguous	0.74	Ambiguous	1.09	Destabilizing	0.412	Likely Benign	-1.96	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	3.06	Benign	0.01	Affected			0.0864	0.3588		2	2	0.7	0.00
c.199C>A	L67I 2D AIThe SynGAP1 missense variant L67I 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the variant, 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		0.458154	Structured	0.473668	Uncertain	0.428	0.761	0.125											-4.387	Likely Benign	0.307	Likely Benign	Likely Benign										0.084	Likely Benign	-0.29	Neutral	0.458	Possibly Damaging	0.364	Benign	4.10	Benign	0.00	Affected			0.0680	0.2919		2	2	0.7	0.00
c.2017C>A	L673I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L673I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The remaining tools (FoldX, Rosetta, Foldetta, ESM1b) return uncertain or inconclusive results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Taken together, the majority of reliable predictors indicate a benign effect, and there is no conflict with ClinVar status (which has no entry). Therefore, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000											-7.823	In-Between	0.099	Likely Benign	Likely Benign	1.51	Ambiguous	0.2	1.89	Ambiguous	1.70	Ambiguous	-0.02	Likely Benign	0.036	Likely Benign	-0.14	Neutral	0.535	Possibly Damaging	0.112	Benign	3.37	Benign	0.47	Tolerated			0.0910	0.3689		2	2	0.7	0.00
c.2065C>A	L689I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689I is not 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, AlphaMissense‑Optimized, and polyPhen2_HumVar, while those that predict a pathogenic effect are polyPhen2_HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also unavailable. No folding‑stability evidence supports a deleterious change. Overall, the balance of evidence slightly favors a benign interpretation, 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	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000											-11.196	Likely Pathogenic	0.677	Likely Pathogenic	Likely Benign	1.71	Ambiguous	0.1	1.12	Ambiguous	1.42	Ambiguous	0.85	Ambiguous	0.180	Likely Benign	-1.97	Neutral	0.822	Possibly Damaging	0.381	Benign	3.44	Benign	0.00	Affected			0.0921	0.3479		2	2	0.7	0.00
c.2083C>A	L695I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, SIFT, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic outcome. The remaining tools—AlphaMissense‑Default, Foldetta, premPS, and Rosetta—return 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) also yields a benign prediction, whereas Foldetta remains uncertain. Overall, the majority of reliable predictions support 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	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000											-12.096	Likely Pathogenic	0.395	Ambiguous	Likely Benign	0.47	Likely Benign	0.1	0.63	Ambiguous	0.55	Ambiguous	0.93	Ambiguous	0.251	Likely Benign	-2.00	Neutral	0.996	Probably Damaging	0.905	Possibly Damaging	3.24	Benign	0.08	Tolerated			0.0815	0.2759		2	2	0.7	0.00
c.2086C>A	L696I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696I missense change is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. FoldX, Rosetta, Foldetta, and premPS give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is unavailable. Overall, the majority of conventional tools lean toward pathogenicity, and the high‑accuracy prediction that is available (AlphaMissense‑Optimized) indicates benign, leaving the evidence mixed. Thus, the variant is most likely pathogenic based on the preponderance of predictions, and this does not contradict the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000											-10.652	Likely Pathogenic	0.698	Likely Pathogenic	Likely Benign	1.01	Ambiguous	0.1	0.58	Ambiguous	0.80	Ambiguous	0.85	Ambiguous	0.250	Likely Benign	-1.86	Neutral	0.996	Probably Damaging	0.989	Probably Damaging	3.15	Benign	0.00	Affected			0.0921	0.2542		2	2	0.7	0.00
c.2107C>A	L703I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and Rosetta. Predictions that are uncertain or inconclusive (FoldX, Foldetta, premPS, AlphaMissense‑Default) are treated as unavailable. 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 high‑confidence tools predict a benign impact, and this conclusion does not contradict the ClinVar status, which has no pathogenic classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000											-9.332	Likely Pathogenic	0.345	Ambiguous	Likely Benign	1.44	Ambiguous	0.1	2.21	Destabilizing	1.83	Ambiguous	0.61	Ambiguous	0.108	Likely Benign	-1.50	Neutral	0.982	Probably Damaging	0.758	Possibly Damaging	3.38	Benign	0.00	Affected			0.0909	0.3079		2	2	0.7	0.00
c.2122C>A	L708I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L708I is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the substitution as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, premPS, FoldX, Rosetta, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and FATHMM. No tool predicts pathogenicity. High‑accuracy assessments concur: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also reports a benign effect. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.365875	Uncertain	0.931	0.378	0.000											-4.406	Likely Benign	0.116	Likely Benign	Likely Benign	0.42	Likely Benign	0.0	-0.21	Likely Benign	0.11	Likely Benign	-0.05	Likely Benign	0.108	Likely Benign	0.02	Neutral	0.022	Benign	0.021	Benign	3.34	Benign	0.20	Tolerated			0.0749	0.2729		2	2	0.7	0.00
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.2152C>A	L718I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718I is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Three tools (Foldetta, premPS, Rosetta) give uncertain results and are not considered evidence. High‑accuracy methods specifically show AlphaMissense‑Optimized as benign, SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Because the majority of reliable predictors (eight out of eleven) indicate pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000											-10.560	Likely Pathogenic	0.615	Likely Pathogenic	Likely Benign	2.21	Destabilizing	0.2	1.37	Ambiguous	1.79	Ambiguous	0.89	Ambiguous	0.296	Likely Benign	-1.90	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	1.37	Pathogenic	0.00	Affected			0.0876	0.3206		2	2	0.7	0.00
c.2287C>A	L763I 2D AIThe SynGAP1 missense variant L763I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and there is 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		0.380708	Structured	0.918636	Binding	0.351	0.865	0.125											-4.803	Likely Benign	0.150	Likely Benign	Likely Benign										0.052	Likely Benign	-0.55	Neutral	0.877	Possibly Damaging	0.675	Possibly Damaging	2.48	Pathogenic	0.31	Tolerated			0.0870	0.3367		2	2	0.7	0.00
c.2305C>A	L769I 2D AIThe SynGAP1 missense variant L769I is listed in gnomAD (ID 6‑33442463‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250								6-33442463-C-A			-3.993	Likely Benign	0.110	Likely Benign	Likely Benign										0.099	Likely Benign	-0.15	Neutral	0.836	Possibly Damaging	0.329	Benign	4.09	Benign	0.04	Affected	3.64	6	0.0800	0.3108		2	2	0.7	0.00
c.2329C>A	L777I 2D AIThe SynGAP1 missense variant L777I is listed in gnomAD (ID 6‑33442487‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which reports “Likely Benign.” Pathogenic predictions are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for the variant, 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		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250								6-33442487-C-A			-5.346	Likely Benign	0.128	Likely Benign	Likely Benign										0.096	Likely Benign	-0.85	Neutral	0.843	Possibly Damaging	0.920	Probably Damaging	4.05	Benign	0.02	Affected	3.64	6	0.1041	0.4327		2	2	0.7	0.00
c.2356C>A	L786I 2D AIThe SynGAP1 missense variant L786I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome 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 evidence, especially from the high‑accuracy methods, points to a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750											-5.464	Likely Benign	0.215	Likely Benign	Likely Benign										0.087	Likely Benign	-1.12	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.93	Pathogenic	0.00	Affected			0.1056	0.4199		2	2	0.7	0.00
c.2536T>A	L846I 2D AIThe SynGAP1 missense variant L846I is not 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 predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. For high‑accuracy assessment, AlphaMissense‑Optimized classifies the variant as benign. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive because the votes are split (one pathogenic, one benign, two uncertain). Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available output for this variant. Overall, the balance of evidence from the majority of prediction tools suggests 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.			0.653063	Disordered	0.589606	Binding	0.349	0.825	0.500											-7.882	In-Between	0.474	Ambiguous	Likely Benign										0.151	Likely Benign	-1.38	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.18	Pathogenic	0.00	Affected			0.0973	0.3475		2	2	0.7	0.00
c.2563C>A	L855I 2D AIThe SynGAP1 missense variant L855I is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess functional impact all converge on a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. No tool in the dataset indicates pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Consequently, the variant is most likely benign based on the collective predictions, and this 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		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625											-4.721	Likely Benign	0.093	Likely Benign	Likely Benign										0.071	Likely Benign	-0.63	Neutral	0.004	Benign	0.008	Benign	4.08	Benign	0.35	Tolerated			0.0981	0.3893		2	2	0.7	0.00
c.2647C>A	L883I 2D AIThe SynGAP1 missense variant L883I 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, 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, 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		0.716283	Disordered	0.641952	Binding	0.334	0.886	0.250											-5.046	Likely Benign	0.102	Likely Benign	Likely Benign										0.049	Likely Benign	-0.26	Neutral	0.802	Possibly Damaging	0.355	Benign	2.66	Benign	0.35	Tolerated			0.0970	0.4093		2	2	0.7	0.00
c.2671C>A	L891I 2D AIThe SynGAP1 missense variant L891I is not reported 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, 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 also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750											-5.803	Likely Benign	0.099	Likely Benign	Likely Benign										0.048	Likely Benign	-0.71	Neutral	0.481	Possibly Damaging	0.202	Benign	2.74	Benign	0.14	Tolerated			0.0957	0.3494		2	2	0.7	0.00
c.2716C>A	L906I 2D AIThe SynGAP1 missense variant L906I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; no Foldetta stability result is available. Overall, the majority of evidence points to a benign impact for this variant. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250											-5.882	Likely Benign	0.174	Likely Benign	Likely Benign										0.036	Likely Benign	-0.50	Neutral	0.905	Possibly Damaging	0.545	Possibly Damaging	2.45	Pathogenic	0.32	Tolerated			0.1060	0.4093		2	2	0.7	0.00
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.2791C>A	L931I 2D AIThe SynGAP1 missense variant L931I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 HumDiv and polyPhen‑2 HumVar both 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 predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from multiple prediction algorithms indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar reporting. 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											-3.813	Likely Benign	0.296	Likely Benign	Likely Benign										0.120	Likely Benign	0.42	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.58	Benign	0.14	Tolerated			0.1076	0.3540		2	2	0.7	0.00
c.2962C>A	L988I 2D AIThe SynGAP1 missense variant L988I 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		0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750											-4.226	Likely Benign	0.204	Likely Benign	Likely Benign										0.120	Likely Benign	-1.08	Neutral	0.924	Possibly Damaging	0.652	Possibly Damaging	2.70	Benign	0.00	Affected			0.1034	0.4143		2	2	0.7	0.00
c.3001C>A	L1001I 2D AIThe SynGAP1 missense variant L1001I is not 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools 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		0.754692	Disordered	0.958507	Binding	0.269	0.902	0.375											-4.486	Likely Benign	0.076	Likely Benign	Likely Benign										0.034	Likely Benign	-0.17	Neutral	0.022	Benign	0.018	Benign	2.69	Benign	0.00	Affected			0.0994	0.3264		2	2	0.7	0.00
c.3064C>A	L1022I 2D AIThe SynGAP1 missense variant L1022I 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 supports a benign classification, 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		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500											-4.624	Likely Benign	0.166	Likely Benign	Likely Benign										0.025	Likely Benign	-0.91	Neutral	0.114	Benign	0.072	Benign	2.58	Benign	0.11	Tolerated			0.1081	0.4395		2	2	0.7	0.00
c.3070C>A	L1024I 2D AIThe SynGAP1 missense variant L1024I is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and FATHMM predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. 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		0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500											-4.794	Likely Benign	0.260	Likely Benign	Likely Benign										0.062	Likely Benign	-0.99	Neutral	0.959	Probably Damaging	0.642	Possibly Damaging	2.45	Pathogenic	0.11	Tolerated			0.0992	0.3735		2	2	0.7	0.00
c.3271C>A	L1091I 2D AIThe SynGAP1 missense variant L1091I is reported in gnomAD (ID 6‑33443823‑C‑A) but has no ClinVar entry. Across the available in‑silico predictors, every tool classified the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all returned benign scores. No tool predicted pathogenicity, so the pathogenic‑prediction group is empty. High‑accuracy assessments reinforce this benign view: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available for this variant. Overall, the computational evidence strongly supports a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000								6-33443823-C-A			-4.304	Likely Benign	0.273	Likely Benign	Likely Benign										0.057	Likely Benign	-0.66	Neutral	0.186	Benign	0.055	Benign	2.55	Benign	0.13	Tolerated	3.77	5	0.1073	0.3911		2	2	0.7	0.00
c.3325C>A	L1109I 2D AIThe SynGAP1 missense variant L1109I 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 is consistent with the lack of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875											-5.475	Likely Benign	0.073	Likely Benign	Likely Benign										0.058	Likely Benign	-0.40	Neutral	0.126	Benign	0.040	Benign	2.70	Benign	0.23	Tolerated			0.1087	0.4703		2	2	0.7	0.00
c.3511_3512delinsTG	A1171C 2D AIThe SynGAP1 missense variant A1171C (ClinVar ID 1723483.0) is listed as “Uncertain” in ClinVar and is not present in gnomAD. Prediction tools that converge on a benign outcome include PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which report a benign or neutral effect. In contrast, PolyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign,” reinforcing the benign signal. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote) as benign, and Foldetta results are unavailable. 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	Coiled-coil	0.599170	Disordered	0.702689	Binding	0.472	0.775	0.500					Uncertain		1				-5.363	Likely Benign	0.496	Ambiguous	Likely Benign												-1.16	Neutral	0.978	Probably Damaging	0.825	Possibly Damaging	5.32	Benign	0.02	Affected	4.32	4	0.1102	0.4921		-2	0	0.7	32.06
c.3538C>A	L1180I 2D AIThe SynGAP1 missense variant L1180I is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign effect. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for the variant, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250											-4.553	Likely Benign	0.697	Likely Pathogenic	Likely Benign										0.086	Likely Benign	-0.67	Neutral	0.856	Possibly Damaging	0.578	Possibly Damaging	2.69	Benign	0.00	Affected			0.0825	0.2708		2	2	0.7	0.00
c.3742C>A	L1248I 2D AIThe SynGAP1 missense variant L1248I 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, whereas pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments are less decisive: AlphaMissense‑Optimized returns an uncertain result, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie and thus unavailable, and Foldetta data are missing. Consequently, the overall evidence leans toward pathogenicity, but the lack of definitive high‑accuracy support and the absence of ClinVar annotation mean the prediction is not contradicted by existing clinical databases. 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											-6.928	Likely Benign	0.872	Likely Pathogenic	Ambiguous										0.173	Likely Benign	-1.56	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.75	Pathogenic	0.00	Affected			0.0919	0.2413		2	2	0.7	0.00
c.3874C>A	L1292I 2D AIThe SynGAP1 missense variant L1292I 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 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		0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625											-5.480	Likely Benign	0.135	Likely Benign	Likely Benign										0.050	Likely Benign	0.71	Neutral	0.002	Benign	0.006	Benign	3.23	Benign	1.00	Tolerated			0.1101	0.3323		2	2	0.7	0.00
c.3895C>A	L1299I 2D AIThe SynGAP1 missense variant L1299I 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 results are unavailable. Based on the collective predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750											-5.264	Likely Benign	0.116	Likely Benign	Likely Benign										0.396	Likely Benign	0.71	Neutral	0.003	Benign	0.004	Benign	3.20	Benign	1.00	Tolerated			0.1014	0.3893		2	2	0.7	0.00
c.409C>A	L137I 2D AIThe SynGAP1 missense variant L137I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs. 3 benign) indicate a likely pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375											-8.870	Likely Pathogenic	0.914	Likely Pathogenic	Ambiguous										0.113	Likely Benign	-1.22	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.73	Benign	0.00	Affected			0.0932	0.3102		2	2	0.7	0.00
c.448C>A	L150I 2D AIThe SynGAP1 missense variant L150I is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas those that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments are less definitive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta results are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a likely pathogenic impact for the variant. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.494003	Structured	0.505752	Binding	0.299	0.839	0.625											-10.118	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous										0.080	Likely Benign	-1.25	Neutral	0.993	Probably Damaging	0.967	Probably Damaging	3.74	Benign	0.00	Affected			0.0894	0.3468		2	2	0.7	0.00
c.592C>A	L198I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L198I is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain or inconclusive results come from AlphaMissense‑Default, FoldX, Rosetta, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, while Foldetta remains uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.444081	Structured	0.431715	Uncertain	0.572	0.485	0.125											-10.411	Likely Pathogenic	0.563	Ambiguous	Likely Benign	0.59	Ambiguous	0.1	0.70	Ambiguous	0.65	Ambiguous	0.10	Likely Benign	0.234	Likely Benign	-1.72	Neutral	0.990	Probably Damaging	0.760	Possibly Damaging	3.43	Benign	0.00	Affected			0.0921	0.3307		2	2	0.7	0.00
c.790C>A	L264I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L264I is not reported in ClinVar and is present in gnomAD (ID 6‑33437695‑C‑A). Prediction tools that indicate a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default 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 Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus remains pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the balance of evidence—six pathogenic versus three benign predictions, a pathogenic SGM Consensus, and an uncertain Foldetta—suggests that the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000								6-33437695-C-A	1	6.20e-7	-10.945	Likely Pathogenic	0.638	Likely Pathogenic	Likely Benign	1.90	Ambiguous	0.5	0.84	Ambiguous	1.37	Ambiguous	0.95	Ambiguous	0.418	Likely Benign	-1.84	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	0.66	Pathogenic	0.02	Affected	3.38	18	0.0764	0.2630		2	2	0.7	0.00
c.850C>A	L284I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L284I missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No evidence from FoldX or Rosetta alone is conclusive. Overall, the majority of predictions, including the high‑accuracy methods, support a benign classification. This consensus 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	C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000											-5.853	Likely Benign	0.293	Likely Benign	Likely Benign	0.50	Ambiguous	0.0	1.22	Ambiguous	0.86	Ambiguous	0.49	Likely Benign	0.364	Likely Benign	-1.51	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.88	Pathogenic	0.13	Tolerated			0.0738	0.3006		2	2	0.7	0.00
c.1045C>T	P349S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P349S missense variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Predictions that are inconclusive or uncertain are FoldX, ESM1b, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of tools, including the high‑accuracy methods, predict a pathogenic effect. Thus, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000					Uncertain		1				-7.654	In-Between	0.217	Likely Benign	Likely Benign	1.92	Ambiguous	0.1	2.28	Destabilizing	2.10	Destabilizing	0.87	Ambiguous	0.277	Likely Benign	-6.13	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.66	Pathogenic	0.06	Tolerated	3.37	25	0.3771	0.5756		1	-1	0.8	-10.04	194.9	-18.1	-0.1	0.0	0.2	0.1	X						X	Potentially Pathogenic	The cyclic pyrrolidine side chain of Pro349, located at the end of an anti-parallel β sheet strand (res. Gly341-Pro349), allows the strand to end and make a tight turn before a short α helical section within a loop connecting to another β strand (res. Thr359-Pro364). In the variant simulations, the hydroxyl group of Ser349 forms a hydrogen bond with the backbone amide group of Ala351 in the short helical section. Conversely, the backbone amide group of Ser349 (absent in proline) does not form any intra-protein hydrogen bonds. However, the β strand end connects to the α helical section in a more stable and consistent manner compared to the WT. Although the residue swap does not cause major adverse effects on the protein structure in the simulations, it is possible that the tight turn at the β strand end could not be created during folding without the presence of proline.
c.1090C>T	P364S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P364S resides in the C2 domain. It is not reported in ClinVar and is present in gnomAD (ID 6‑33437995‑C‑T). Prediction tools that classify the variant as benign include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM; the SGM‑Consensus score is also labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. No prediction or stability result is missing or inconclusive beyond the Uncertain labels. Based on the majority of 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	C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250								6-33437995-C-T	1	6.20e-7	-8.318	Likely Pathogenic	0.214	Likely Benign	Likely Benign	1.34	Ambiguous	0.3	0.68	Ambiguous	1.01	Ambiguous	0.83	Ambiguous	0.307	Likely Benign	-5.98	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.62	Pathogenic	0.05	Affected	3.39	20	0.3390	0.5512		-1	1	0.8	-10.04
c.1102C>T	P368S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P368S is not 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and FATHMM. The remaining methods (FoldX, Rosetta, Foldetta, premPS) yield 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 uncertain, so these do not alter the overall interpretation. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict the current ClinVar status. 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											-4.790	Likely Benign	0.247	Likely Benign	Likely Benign	1.68	Ambiguous	0.4	1.60	Ambiguous	1.64	Ambiguous	0.52	Ambiguous	0.090	Likely Benign	-5.12	Deleterious	0.384	Benign	0.113	Benign	1.80	Pathogenic	0.10	Tolerated			0.3700	0.5635		1	-1	0.8	-10.04
c.112C>T	P38S 2D AIThe SynGAP1 missense variant P38S is not reported 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 because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.433285	Uncertain	0.344	0.791	0.375											-2.727	Likely Benign	0.104	Likely Benign	Likely Benign										0.101	Likely Benign	-2.13	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.13	Benign	0.00	Affected			0.3837	0.6111		1	-1	0.8	-10.04
c.1192C>T	P398S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P398S 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 polyPhen‑2 (HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv), and SIFT. The remaining tools (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of definitive predictions lean toward 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.		C2	0.436924	Structured	0.401041	Uncertain	0.891	0.525	0.250											-6.757	Likely Benign	0.490	Ambiguous	Likely Benign	1.86	Ambiguous	0.3	1.78	Ambiguous	1.82	Ambiguous	0.85	Ambiguous	0.544	Likely Pathogenic	-5.58	Deleterious	0.478	Possibly Damaging	0.130	Benign	5.68	Benign	0.03	Affected			0.3619	0.5737		1	-1	0.8	-10.04
c.1237C>T	P413S 2D 3DClick to see structure in 3D Viewer AISynGAP1 P413S is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include only FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—indicate a pathogenic effect. High‑accuracy methods give a consistent pathogenic verdict: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) predicts pathogenic; FoldX alone supports pathogenicity while Rosetta remains uncertain. Taken together, the overwhelming majority of predictions support a pathogenic classification, and this is not contradicted by the absence of a ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-12.586	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	3.06	Destabilizing	0.1	1.72	Ambiguous	2.39	Destabilizing	0.93	Ambiguous	0.509	Likely Pathogenic	-7.37	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.19	Benign	0.04	Affected			0.3454	0.3819		1	-1	0.8	-10.04
c.124C>T	P42S 2D AIThe SynGAP1 missense variant P42S is listed in gnomAD (ID 6‑33423533‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for P42S, and this conclusion is not contradicted by ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.308712	Structured	0.431487	Uncertain	0.420	0.771	0.375								6-33423533-C-T	1	6.20e-7	-3.472	Likely Benign	0.109	Likely Benign	Likely Benign										0.048	Likely Benign	-1.12	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.24	Benign	0.00	Affected	4.32	1	0.3462	0.4470		-1	1	0.8	-10.04
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.136C>T	P46S 2D AIThe SynGAP1 missense variant P46S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, which aggregates the majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence—including high‑accuracy tools—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		0.390993	Structured	0.433588	Uncertain	0.549	0.741	0.375					Uncertain		1				-3.338	Likely Benign	0.302	Likely Benign	Likely Benign										0.066	Likely Benign	-0.60	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.15	Benign	0.00	Affected			0.3904	0.5771		1	-1	0.8	-10.04
c.1582C>T	P528S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P528S missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic calls are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only FATHMM predicts a benign outcome. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) remains Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is inconclusive. No folding‑stability metrics (FoldX, Rosetta, premPS) provide definitive evidence. Overall, the preponderance of pathogenic predictions suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-11.729	Likely Pathogenic	0.819	Likely Pathogenic	Ambiguous	1.88	Ambiguous	0.1	1.28	Ambiguous	1.58	Ambiguous	0.80	Ambiguous	0.617	Likely Pathogenic	-7.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.52	Benign	0.01	Affected			0.3115	0.3982		1	-1	0.8	-10.04
c.1684C>T	P562S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P562S is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict pathogenicity. The only tools with uncertain outcomes are Rosetta and premPS, which provide inconclusive results. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022306	Structured	0.023606	Uncertain	0.893	0.200	0.000											-14.293	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	2.93	Destabilizing	0.1	1.59	Ambiguous	2.26	Destabilizing	0.70	Ambiguous	0.708	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.62	Pathogenic	0.01	Affected			0.3365	0.2900		1	-1	0.8	-10.04
c.1798C>T	P600S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P600S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include Rosetta and Foldetta, whereas the majority of other in‑silico predictors (REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict it to be pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) as benign. No contradictory evidence exists in ClinVar. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.162960	Uncertain	0.947	0.147	0.000											-12.002	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	2.54	Destabilizing	0.1	-2.60	Stabilizing	-0.03	Likely Benign	0.52	Ambiguous	0.717	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.40	Pathogenic	0.01	Affected			0.3744	0.4200		1	-1	0.8	-10.04
c.1813C>T	P605S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605S is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All evaluated in‑silico predictors classify the change as pathogenic: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the unanimous pathogenic predictions, the variant is most likely pathogenic, which contradicts the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000					Uncertain		1				-10.830	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	3.40	Destabilizing	0.1	3.34	Destabilizing	3.37	Destabilizing	1.00	Destabilizing	0.718	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.70	Pathogenic	0.00	Affected	3.37	35	0.3397	0.4676		1	-1	0.8	-10.04	213.8	-15.4	-0.3	0.2	0.2	0.1				X			X	Potentially Pathogenic	Pro605 is located in a short turn between an α helix (res. Glu582-Met603) and a short α helical section (res. Ser606-Phe608). The pyrrolidine side chain of Pro605 packs hydrophobically with nearby hydrophobic residues (e.g., Ile514, Leu623, Leu610) in the inter-helix space. Additionally, proline lacks a free backbone amide group, which breaks the α helix and facilitates the turn in the WT structure.In the variant simulations, the hydroxyl side chain of Ser605 forms hydrogen bonds with the backbone carbonyl groups of Ala601 and Ile602. Importantly, the helix end is more stable than with Pro605 in the WT. Indeed, proline is a more effective secondary structure breaker compared to serine.Thus, the residue swap could have a more profound effect on the actual folding process, for example, by preventing the bending at the α helix end, than what the simulations suggest. Moreover, due to its location at the GAP-Ras interface, the residue swap could affect the GAP-Ras association.
c.1843C>T	P615S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P615S is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a pathogenic effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM Consensus also indicates a likely pathogenic outcome. No tools predict a benign effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, while Foldetta’s stability prediction is uncertain and therefore not taken as evidence. Overall, the preponderance of evidence points to the variant being most likely pathogenic, with no contradiction to the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.236433	Structured	0.179032	Uncertain	0.879	0.255	0.000											-12.566	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	2.46	Destabilizing	0.3	1.28	Ambiguous	1.87	Ambiguous	0.98	Ambiguous	0.780	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.19	Pathogenic	0.04	Affected			0.3191	0.3310		1	-1	0.8	-10.04
c.196C>T	P66S 2D AIThe SynGAP1 missense variant P66S is listed in ClinVar (ID 1915017.0) as benign and is present in gnomAD (variant ID 6‑33425804‑C‑T). 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. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains likely benign; Foldetta results are unavailable. Overall, the balance of evidence favors a benign interpretation, which is consistent with the ClinVar designation and does not contradict the reported status. 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					Benign		1	6-33425804-C-T	2	1.24e-6	-2.760	Likely Benign	0.929	Likely Pathogenic	Ambiguous										0.081	Likely Benign	-1.69	Neutral	0.909	Possibly Damaging	0.641	Possibly Damaging	4.01	Benign	0.00	Affected	4.32	1	0.3417	0.5463		1	-1	0.8	-10.04
c.2101C>T	P701S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P701S (ClinVar ID 2995856.0) is listed as “Uncertain” in ClinVar and is present in gnomAD (ID 6‑33441360‑C‑T). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). No tool in the dataset predicts a pathogenic outcome; all remaining predictions are either benign or uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000					Uncertain		1	6-33441360-C-T	3	1.86e-6	-4.375	Likely Benign	0.221	Likely Benign	Likely Benign	1.33	Ambiguous	0.0	0.12	Likely Benign	0.73	Ambiguous	-0.36	Likely Benign	0.132	Likely Benign	0.78	Neutral	0.044	Benign	0.025	Benign	3.48	Benign	1.00	Tolerated	3.47	10	0.3149	0.3782		-1	1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2137C>T	P713S 2D AIThe SynGAP1 missense variant P713S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, Rosetta, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain results are provided by FoldX, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this ambiguity: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates a likely pathogenic effect, and Foldetta likewise yields an uncertain stability change. Overall, the majority of tools lean toward a pathogenic interpretation, and this aligns 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	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000											-8.496	Likely Pathogenic	0.846	Likely Pathogenic	Ambiguous	0.91	Ambiguous	0.7	0.19	Likely Benign	0.55	Ambiguous	0.62	Ambiguous	0.261	Likely Benign	-6.60	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.00	Affected			0.3234	0.3674		1	-1	0.8	-10.04
c.2143C>T	P715S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P715S is listed in ClinVar as pathogenic (ClinVar ID 1804065.0) and is present in gnomAD (ID 6‑33441608‑C‑T). Functional prediction tools that agree on a benign effect are REVEL and FATHMM. Those that predict a pathogenic effect include FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Predictions that are inconclusive are Rosetta, premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of evidence points to a pathogenic impact, which is consistent with the ClinVar classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000					Likely Pathogenic		1	6-33441608-C-T	1	6.20e-7	-7.635	In-Between	0.787	Likely Pathogenic	Ambiguous	3.54	Destabilizing	0.0	0.81	Ambiguous	2.18	Destabilizing	0.94	Ambiguous	0.277	Likely Benign	-7.17	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.43	Benign	0.01	Affected	3.50	9	0.2977	0.3755		1	-1	0.8	-10.04	231.8	-14.0	-0.1	0.0	-0.8	0.1							X	Uncertain	Pro715, along with Gly712 and Pro713, are located in a hinge region of an α-helix making a ~90-degree turn (res. Lys705-Leu725). In the WT simulations, the pyrrolidine side chain of Pro715, lacking the backbone amide groups altogether, forces the tight helix turn to take place while also hydrophobically packing with nearby residues (e.g., Leu700, Leu708, Leu714, and Leu718). Leu715, with a normal amide backbone, could potentially affect protein folding and turn formation, although this was not observed in the variant simulations. Additionally, the hydroxyl group of the Ser715 side chain can form hydrogen bonds with the backbone carbonyl group of Gly712 and disrupt the hydrophobic packing arrangement of the leucine residues from the neighboring α-helices, impacting the GAP domain tertiary assembly.
c.2182C>T	P728S 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P728S is not reported in ClinVar and is present in gnomAD (ID 6‑33441647‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, whereas the majority of tools predict pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results from FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized are treated as unavailable. High‑accuracy consensus methods give a Likely Pathogenic verdict from the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and an Uncertain outcome from AlphaMissense‑Optimized; Foldetta also reports Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P728S, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625								6-33441647-C-T	1	6.20e-7	-9.047	Likely Pathogenic	0.897	Likely Pathogenic	Ambiguous	0.89	Ambiguous	0.0	0.98	Ambiguous	0.94	Ambiguous	0.54	Ambiguous	0.280	Likely Benign	-6.38	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.68	Pathogenic	0.00	Affected	3.59	7	0.3571	0.3571		-1	1	0.8	-10.04
c.2200C>T	P734S 2D AIThe SynGAP1 missense variant P734S is listed in ClinVar with an uncertain significance (ClinVar ID 2283225.0) and is present in the gnomAD database (gnomAD ID 6‑33441665‑C‑T). 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 report benign effects. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this benign assessment: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports a benign classification, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.411273	Uncertain	0.368	0.721	0.875					Uncertain		2	6-33441665-C-T	2	1.24e-6	-4.291	Likely Benign	0.077	Likely Benign	Likely Benign										0.030	Likely Benign	-2.44	Neutral	0.344	Benign	0.048	Benign	2.77	Benign	0.11	Tolerated	3.64	6	0.3775	0.3650		1	-1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2221C>T	P741S 2D AIThe SynGAP1 missense variant P741S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441686‑C‑T). 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. Grouping by consensus, the benign‑predicting tools outnumber the pathogenic one. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No Foldetta stability data are available, so it does not influence the conclusion. Overall, the computational evidence indicates that 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		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875					Uncertain		2	6-33441686-C-T	3	1.86e-6	-3.700	Likely Benign	0.063	Likely Benign	Likely Benign										0.076	Likely Benign	-0.27	Neutral	0.270	Benign	0.136	Benign	2.92	Benign	0.00	Affected	4.32	2	0.2888	0.4278		1	-1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2227C>T	P743S 2D AIThe SynGAP1 missense variant P743S is listed in gnomAD (ID 6‑33441692‑C‑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, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all classify the change as benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments further support benignity: 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 indicates that P743S is most likely benign, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.526809	Binding	0.317	0.862	0.875								6-33441692-C-T	1	6.19e-7	-4.286	Likely Benign	0.063	Likely Benign	Likely Benign										0.085	Likely Benign	-0.33	Neutral	0.021	Benign	0.015	Benign	2.93	Benign	0.00	Affected	4.32	2	0.3087	0.3948		-1	1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.2233C>T	P745S 2D AIThe SynGAP1 missense variant P745S is reported in gnomAD (variant ID 6-33441698-C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods points to a benign effect for P745S, 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		0.791621	Disordered	0.558331	Binding	0.341	0.860	0.875								6-33441698-C-T	1	6.19e-7	-4.300	Likely Benign	0.077	Likely Benign	Likely Benign										0.160	Likely Benign	-2.32	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.54	Benign	0.05	Affected	4.32	2	0.3397	0.3882		-1	1	0.8	-10.04
c.2251C>T	P751S 2D AIThe SynGAP1 missense variant P751S 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 Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions indicate that P751S 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	0.667683	Binding	0.386	0.866	0.625											-4.157	Likely Benign	0.109	Likely Benign	Likely Benign										0.109	Likely Benign	-0.80	Neutral	0.514	Possibly Damaging	0.216	Benign	2.70	Benign	0.33	Tolerated			0.3446	0.5837		1	-1	0.8	-10.04
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.2380C>T	P794S 2D AIThe SynGAP1 missense variant P794S 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 not available, so they do not influence the assessment. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.979741	Disordered	0.408951	Uncertain	0.550	0.898	0.875											-5.086	Likely Benign	0.079	Likely Benign	Likely Benign										0.041	Likely Benign	-0.21	Neutral	0.025	Benign	0.010	Benign	4.29	Benign	0.13	Tolerated			0.3666	0.5604		1	-1	0.8	-10.04
c.2383C>T	P795S 2D AIThe SynGAP1 missense variant P795S is catalogued in gnomAD (6‑33442935‑C‑T) but has no entry in ClinVar. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently scores the variant as benign. No pathogenic predictions are reported. Grouping by agreement, all available tools fall into the benign category, with no tools indicating pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta results are not provided, so they are treated as unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875								6-33442935-C-T	1	6.20e-7	-5.846	Likely Benign	0.067	Likely Benign	Likely Benign										0.056	Likely Benign	-0.23	Neutral	0.001	Benign	0.002	Benign	4.30	Benign	0.24	Tolerated	4.32	2	0.3517	0.5766		-1	1	0.8	-10.04
c.2386C>T	P796S 2D AIThe SynGAP1 missense variant P796S 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. 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	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-5.382	Likely Benign	0.067	Likely Benign	Likely Benign										0.055	Likely Benign	0.05	Neutral	0.174	Benign	0.091	Benign	4.28	Benign	0.48	Tolerated			0.3560	0.4171		1	-1	0.8	-10.04
c.2389C>T	P797S 2D AIThe SynGAP1 missense variant P797S 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 tolerated or benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. 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 for P797S, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-6.232	Likely Benign	0.068	Likely Benign	Likely Benign										0.029	Likely Benign	-0.14	Neutral	0.901	Possibly Damaging	0.637	Possibly Damaging	4.25	Benign	0.38	Tolerated			0.3634	0.5228		1	-1	0.8	-10.04
c.2392C>T	P798S 2D AIThe SynGAP1 missense variant P798S 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, 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 benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion 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	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.382	Likely Benign	0.065	Likely Benign	Likely Benign										0.058	Likely Benign	0.14	Neutral	0.818	Possibly Damaging	0.353	Benign	4.28	Benign	0.00	Affected			0.2950	0.4425		1	-1	0.8	-10.04
c.2395C>T	P799S 2D AIThe SynGAP1 missense variant P799S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for P799S, 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	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-4.635	Likely Benign	0.068	Likely Benign	Likely Benign										0.065	Likely Benign	-0.73	Neutral	0.951	Possibly Damaging	0.593	Possibly Damaging	4.26	Benign	0.00	Affected			0.3411	0.4464		1	-1	0.8	-10.04
c.2431C>T	P811S 2D AIThe SynGAP1 missense variant P811S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, and AlphaMissense‑Default remains uncertain. No Foldetta stability assessment is available, so it does not contribute to the evidence. Overall, the preponderance of evidence points to a benign effect for P811S, 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	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-4.733	Likely Benign	0.474	Ambiguous	Likely Benign										0.128	Likely Benign	-1.28	Neutral	0.982	Probably Damaging	0.824	Possibly Damaging	2.79	Benign	0.78	Tolerated			0.3656	0.5960		1	-1	0.8	-10.04
c.2434C>T	P812S 2D AIThe SynGAP1 missense variant P812S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33442986‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default remains uncertain, and no Foldetta stability result is available. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta data are missing. 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	SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125					Uncertain		1	6-33442986-C-T	1	6.20e-7	-5.689	Likely Benign	0.456	Ambiguous	Likely Benign										0.162	Likely Benign	-0.62	Neutral	0.999	Probably Damaging	0.966	Probably Damaging	2.89	Benign	0.95	Tolerated	4.32	4	0.3417	0.5699		1	-1	0.8	-10.04
c.2452C>T	P818S 2D AIThe SynGAP1 missense variant P818S is catalogued in gnomAD (ID 6‑33443004‑C‑T) but has no ClinVar entry. Functional prediction tools split in two groups: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The consensus predictor SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments are limited: AlphaMissense‑Optimized yields an uncertain result, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available prediction for this residue. Taken together, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status because none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625								6-33443004-C-T	1	6.20e-7	-5.740	Likely Benign	0.932	Likely Pathogenic	Ambiguous										0.203	Likely Benign	-4.38	Deleterious	0.989	Probably Damaging	0.824	Possibly Damaging	2.04	Pathogenic	0.04	Affected	3.77	5	0.3581	0.6199		-1	1	0.8	-10.04
c.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.2551C>T	P851S 2D AIThe SynGAP1 missense variant P851S is listed in ClinVar (ID 4705230) with an “Uncertain” status and is not reported in 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 pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy tools, indicate that P851S is most likely benign, and this conclusion does not contradict the current ClinVar status of uncertainty. 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					Uncertain		1				-3.696	Likely Benign	0.061	Likely Benign	Likely Benign										0.103	Likely Benign	-0.29	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	4.27	Benign	0.12	Tolerated			0.3498	0.6158		1	-1	0.8	-10.04
c.2653C>T	P885S 2D AIThe SynGAP1 missense variant P885S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.690604	Disordered	0.636133	Binding	0.344	0.917	0.250											-4.089	Likely Benign	0.082	Likely Benign	Likely Benign										0.037	Likely Benign	-1.10	Neutral	0.369	Benign	0.222	Benign	2.87	Benign	0.00	Affected			0.3363	0.5881		1	-1	0.8	-10.04
c.2659C>T	P887S 2D AIThe SynGAP1 missense variant P887S 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 view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions strongly suggest that P887S 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		0.716283	Disordered	0.602269	Binding	0.348	0.925	0.500											-3.462	Likely Benign	0.065	Likely Benign	Likely Benign										0.066	Likely Benign	-1.26	Neutral	0.032	Benign	0.017	Benign	2.85	Benign	0.25	Tolerated			0.2770	0.3946		1	-1	0.8	-10.04
c.265C>T	P89S 2D AIThe SynGAP1 missense variant P89S (ClinVar ID 4801335) is listed as “Uncertain” in ClinVar and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Tools that predict a pathogenic effect are AlphaMissense‑Default, AlphaMissense‑Optimized, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote) remains 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 (six benign vs. three pathogenic) and the SGM‑Consensus support a benign interpretation, which does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500					Uncertain		1				-5.198	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.099	Likely Benign	-2.40	Neutral	0.225	Benign	0.020	Benign	3.76	Benign	0.00	Affected			0.3459	0.4191		1	-1	0.8	-10.04
c.2749C>T	P917S 2D AIThe SynGAP1 missense variant P917S is catalogued in gnomAD (ID 6‑33443301‑C‑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 report benign. Only SIFT predicts pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no reported result for this variant, so it provides no additional evidence. Overall, the preponderance of predictions indicates that P917S is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.863949	Binding	0.314	0.862	0.375								6-33443301-C-T	1	6.20e-7	-3.562	Likely Benign	0.073	Likely Benign	Likely Benign										0.056	Likely Benign	-0.54	Neutral	0.003	Benign	0.002	Benign	2.70	Benign	0.00	Affected	3.77	5	0.3478	0.5121		-1	1	0.8	-10.04
c.2770C>T	P924S 2D AIThe SynGAP1 missense variant P924S is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect for P924S, 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		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-4.686	Likely Benign	0.920	Likely Pathogenic	Ambiguous										0.388	Likely Benign	-5.86	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.2952	0.3772		1	-1	0.8	-10.04
c.2788C>T	P930S 2D AIThe SynGAP1 missense variant P930S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are limited to REVEL, which scores the variant as benign. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that P930S is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-8.439	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.379	Likely Benign	-5.84	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.68	Pathogenic	0.00	Affected			0.3301	0.5457		1	-1	0.8	-10.04
c.280C>T	P94S 2D AIThe SynGAP1 missense variant P94S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33425888‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.570978	Binding	0.350	0.869	0.625					Conflicting		2	6-33425888-C-T	5	3.10e-6	-3.151	Likely Benign	0.084	Likely Benign	Likely Benign										0.093	Likely Benign	-2.36	Neutral	0.092	Benign	0.008	Benign	4.13	Benign	0.00	Affected	4.32	1	0.2823	0.4388		1	-1	0.8	-10.04
c.2815C>T	P939S 2D AIThe SynGAP1 missense variant P939S is not 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 remain unavailable. Overall, the majority of predictions (5 pathogenic vs. 4 benign) indicate that P939S 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.			0.894241	Disordered	0.935841	Binding	0.397	0.897	0.625											-4.331	Likely Benign	0.098	Likely Benign	Likely Benign										0.101	Likely Benign	-3.44	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.24	Pathogenic	0.00	Affected			0.3372	0.4517		1	-1	0.8	-10.04
c.2821C>T	P941S 2D AIThe SynGAP1 missense variant P941S is reported in gnomAD (ID 6‑33443373‑C‑T) but has no ClinVar entry. 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. 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, which evaluates protein‑folding stability via FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of all available predictions indicates that P941S is most likely benign, and this assessment does not contradict any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.900790	Binding	0.403	0.906	0.625								6-33443373-C-T	1	6.20e-7	-5.099	Likely Benign	0.062	Likely Benign	Likely Benign										0.039	Likely Benign	0.58	Neutral	0.036	Benign	0.039	Benign	3.05	Benign	0.95	Tolerated	4.32	4	0.2759	0.5576		-1	1	0.8	-10.04
c.2824C>T	P942S 2D AIThe SynGAP1 missense variant P942S is catalogued in gnomAD (ID 6‑33443376‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, 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, 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		0.919029	Disordered	0.878102	Binding	0.365	0.915	0.625								6-33443376-C-T	1	6.20e-7	-3.919	Likely Benign	0.062	Likely Benign	Likely Benign										0.036	Likely Benign	-0.80	Neutral	0.011	Benign	0.015	Benign	2.43	Pathogenic	0.00	Affected	4.32	4	0.3226	0.4806		-1	1	0.8	-10.04
c.2857C>T	P953S 2D AIThe SynGAP1 missense variant P953S 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, so they do not influence the overall assessment. **Thus, 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		0.983019	Disordered	0.920633	Binding	0.403	0.926	0.750											-5.430	Likely Benign	0.061	Likely Benign	Likely Benign										0.073	Likely Benign	-0.35	Neutral	0.009	Benign	0.008	Benign	2.96	Benign	0.37	Tolerated			0.3359	0.5184		1	-1	0.8	-10.04
c.2860C>T	P954S 2D AIThe SynGAP1 missense variant P954S is listed in ClinVar as Benign (ClinVar ID 833606.0) and is present in gnomAD (ID 6‑33443412‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, which is consistent with the ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984159	Disordered	0.932268	Binding	0.465	0.926	0.750					Likely Benign		1	6-33443412-C-T	1	6.20e-7	-3.525	Likely Benign	0.062	Likely Benign	Likely Benign										0.143	Likely Benign	-0.25	Neutral	0.954	Possibly Damaging	0.812	Possibly Damaging	2.87	Benign	1.00	Tolerated	3.77	5	0.3088	0.5619		1	-1	0.8	-10.04
c.2911C>T	P971S 2D AIThe SynGAP1 missense variant P971S is catalogued in gnomAD (ID 6‑33443463‑C‑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, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate a benign or likely benign outcome. Only SIFT classifies the change as pathogenic, representing a minority opinion. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise reports 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 is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625								6-33443463-C-T	1	6.20e-7	-4.188	Likely Benign	0.061	Likely Benign	Likely Benign										0.058	Likely Benign	-0.51	Neutral	0.002	Benign	0.003	Benign	3.99	Benign	0.00	Affected	4.32	2	0.3009	0.5667		-1	1	0.8	-10.04
c.2914C>T	P972S 2D AIThe SynGAP1 missense variant P972S (ClinVar ID 3361353.0) is listed as Uncertain in ClinVar and is present in gnomAD (ID 6‑33443466‑C‑T). Consensus among most in silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the substitution as benign. Only SIFT classifies it as pathogenic, representing the sole discordant prediction. 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) reports “Likely Benign.” No Foldetta stability analysis is available for this residue. Overall, the preponderance of computational evidence points to a benign effect, which is consistent with the ClinVar designation of uncertainty rather than pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.954150	Binding	0.472	0.904	0.625					Uncertain		1	6-33443466-C-T	4	2.48e-6	-4.008	Likely Benign	0.058	Likely Benign	Likely Benign										0.074	Likely Benign	-0.38	Neutral	0.001	Benign	0.002	Benign	4.28	Benign	0.05	Affected	4.32	2	0.3168	0.4822		-1	1	0.8	-10.04
c.2932C>T	P978S 2D AIThe SynGAP1 missense variant P978S is listed in ClinVar (ID 3379672.0) with an “Uncertain” clinical significance and is not reported in 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 outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions points to a benign 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		0.819762	Disordered	0.975775	Binding	0.425	0.892	0.625					Uncertain		1				-3.913	Likely Benign	0.151	Likely Benign	Likely Benign										0.085	Likely Benign	-1.07	Neutral	0.481	Possibly Damaging	0.220	Benign	4.22	Benign	0.48	Tolerated			0.3428	0.6001		1	-1	0.8	-10.04
c.2977C>T	P993S 2D AIThe SynGAP1 missense variant P993S is reported in gnomAD (ID 6‑33443529‑C‑T) and has no ClinVar entry. All evaluated in silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the unanimous benign predictions and lack of ClinVar pathogenicity, the variant is most likely benign and does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.923979	Binding	0.319	0.908	0.750								6-33443529-C-T	3	1.86e-6	-3.665	Likely Benign	0.068	Likely Benign	Likely Benign										0.054	Likely Benign	-0.13	Neutral	0.011	Benign	0.023	Benign	4.26	Benign	0.59	Tolerated	4.32	2	0.3421	0.5465		-1	1	0.8	-10.04
c.2983C>T	P995S 2D AIThe SynGAP1 missense variant P995S is listed in ClinVar (ID 436929.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). The only tool that predicts a pathogenic outcome is SIFT. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates “Likely Benign.” No Foldetta (FoldX‑MD/Rosetta) stability result is available, so it does not influence the assessment. Overall, the majority of predictions, including the high‑accuracy tools, point to a benign effect, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.935305	Binding	0.338	0.902	0.750					Uncertain		1				-4.457	Likely Benign	0.071	Likely Benign	Likely Benign										0.042	Likely Benign	-1.03	Neutral	0.011	Benign	0.015	Benign	4.24	Benign	0.00	Affected	4.32	1	0.3204	0.5236		1	-1	0.8	-10.04
c.2986C>T	P996S 2D AIThe SynGAP1 missense variant P996S is reported in gnomAD (ID 6‑33443538‑C‑T) and 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 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 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		0.775545	Disordered	0.942262	Binding	0.312	0.900	0.750								6-33443538-C-T	4	2.48e-6	-4.461	Likely Benign	0.063	Likely Benign	Likely Benign										0.064	Likely Benign	-0.58	Neutral	0.002	Benign	0.004	Benign	4.30	Benign	0.09	Tolerated	4.32	4	0.3171	0.5161		-1	1	0.8	-10.04
c.3034C>T	P1012S 2D AIThe SynGAP1 missense variant P1012S is catalogued in gnomAD (ID 6‑33443586‑C‑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 substitution 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 unavailable. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.894674	Binding	0.319	0.866	0.625								6-33443586-C-T	2	1.24e-6	-3.342	Likely Benign	0.087	Likely Benign	Likely Benign										0.044	Likely Benign	-0.23	Neutral	0.224	Benign	0.131	Benign	2.81	Benign	0.22	Tolerated	3.77	5	0.3217	0.5300		-1	1	0.8	-10.04
c.3100C>T	P1034S 2D AIThe SynGAP1 missense variant P1034S 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, 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 P1034S, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.991713	Binding	0.343	0.752	0.625											-3.730	Likely Benign	0.262	Likely Benign	Likely Benign										0.054	Likely Benign	-2.28	Neutral	0.011	Benign	0.015	Benign	2.44	Pathogenic	0.05	Affected			0.3044	0.5853		1	-1	0.8	-10.04
c.3103C>T	P1035S 2D AIThe SynGAP1 missense variant P1035S is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in‑silico tools cluster around a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign. Only polyPhen‑2 HumDiv flags it as pathogenic, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Taken together, the preponderance of evidence points to a benign impact for P1035S, 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		0.945666	Disordered	0.989572	Binding	0.300	0.756	0.625											-3.678	Likely Benign	0.341	Ambiguous	Likely Benign										0.059	Likely Benign	-0.97	Neutral	0.818	Possibly Damaging	0.355	Benign	2.79	Benign	0.28	Tolerated			0.3257	0.6253		1	-1	0.8	-10.04
c.3121C>T	P1041S 2D AIThe SynGAP1 missense variant P1041S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443673‑C‑T). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. 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, and this does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.962114	Disordered	0.967463	Binding	0.345	0.833	0.625					Conflicting		2	6-33443673-C-T	1	6.20e-7	-4.246	Likely Benign	0.121	Likely Benign	Likely Benign										0.344	Likely Benign	-2.72	Deleterious	0.664	Possibly Damaging	0.283	Benign	5.48	Benign	0.11	Tolerated	3.77	5	0.3199	0.6120		1	-1	0.8	-10.04
c.3130C>T	P1044S 2D AIThe SynGAP1 missense variant P1044S 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		0.979741	Disordered	0.952126	Binding	0.331	0.855	0.750											-4.114	Likely Benign	0.078	Likely Benign	Likely Benign										0.311	Likely Benign	-0.79	Neutral	0.011	Benign	0.015	Benign	5.51	Benign	0.14	Tolerated			0.3194	0.6081		1	-1	0.8	-10.04
c.3136C>T	P1046S 2D AIThe SynGAP1 missense variant P1046S is not 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, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of computational evidence indicates a benign effect, and this consensus does not contradict any ClinVar status (none is available). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.970265	Disordered	0.942366	Binding	0.364	0.898	0.750											-3.909	Likely Benign	0.059	Likely Benign	Likely Benign										0.096	Likely Benign	-0.72	Neutral	0.126	Benign	0.096	Benign	2.39	Pathogenic	0.70	Tolerated			0.2929	0.5744		1	-1	0.8	-10.04
c.3145C>T	P1049S 2D AIThe SynGAP1 missense variant P1049S is reported in gnomAD (variant ID 6‑33443697‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic 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. No Foldetta stability data are available, so it does not influence the assessment. Overall, the majority of predictions, including the high‑accuracy tools, indicate that P1049S 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		0.978316	Disordered	0.917915	Binding	0.428	0.920	0.750								6-33443697-C-T	2	1.24e-6	-2.351	Likely Benign	0.053	Likely Benign	Likely Benign										0.071	Likely Benign	-1.53	Neutral	0.519	Possibly Damaging	0.303	Benign	2.76	Benign	0.04	Affected	3.77	5	0.3144	0.5083		-1	1	0.8	-10.04
c.3193C>T	P1065S 2D AIThe SynGAP1 missense variant P1065S 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. 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		0.979741	Disordered	0.959518	Binding	0.424	0.917	0.875											-5.512	Likely Benign	0.076	Likely Benign	Likely Benign										0.041	Likely Benign	-2.07	Neutral	0.770	Possibly Damaging	0.255	Benign	2.06	Pathogenic	0.00	Affected			0.3172	0.6021		1	-1	0.8	-10.04
c.3196C>T	P1066S 2D AIThe SynGAP1 missense variant P1066S is listed in ClinVar as Pathogenic (ClinVar ID 1343237.0) and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, which contradicts the ClinVar pathogenic classification. Thus, based on current predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.967676	Disordered	0.968838	Binding	0.403	0.913	0.875					Likely Pathogenic		1				-4.746	Likely Benign	0.070	Likely Benign	Likely Benign										0.145	Likely Benign	-2.47	Neutral	0.972	Probably Damaging	0.850	Possibly Damaging	2.74	Benign	0.00	Affected	4.32	2	0.3304	0.6353		1	-1	0.8	-10.04
c.3199C>T	P1067S 2D AIThe SynGAP1 missense variant P1067S 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. Based on the collective predictions, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.966441	Disordered	0.975099	Binding	0.459	0.907	0.875											-4.673	Likely Benign	0.073	Likely Benign	Likely Benign										0.079	Likely Benign	-1.43	Neutral	0.271	Benign	0.054	Benign	2.91	Benign	0.48	Tolerated			0.3086	0.5753		1	-1	0.8	-10.04
c.3250C>T	P1084S 2D AIThe SynGAP1 missense variant P1084S is reported in gnomAD (variant ID 6‑33443802‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, 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		0.842060	Disordered	0.979020	Binding	0.348	0.889	1.000								6-33443802-C-T	1	6.31e-7	-3.987	Likely Benign	0.119	Likely Benign	Likely Benign										0.086	Likely Benign	-2.24	Neutral	0.481	Possibly Damaging	0.157	Benign	4.03	Benign	0.03	Affected	3.77	5	0.3102	0.6215		-1	1	0.8	-10.04
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.3283C>T	P1095S 2D AIThe SynGAP1 missense variant P1095S is reported in gnomAD (ID 6‑33443835‑C‑T) and has no ClinVar entry. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Based on the unanimous benign predictions and the absence of any pathogenic signal, 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		0.922952	Disordered	0.979251	Binding	0.387	0.870	1.000								6-33443835-C-T	7	4.51e-6	-3.819	Likely Benign	0.182	Likely Benign	Likely Benign										0.128	Likely Benign	-0.64	Neutral	0.207	Benign	0.072	Benign	2.80	Benign	1.00	Tolerated	3.77	5	0.3150	0.5963		-1	1	0.8	-10.04
c.3289C>T	P1097S 2D AIThe SynGAP1 missense variant P1097S 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 from 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		0.919029	Disordered	0.974957	Binding	0.384	0.858	1.000											-3.748	Likely Benign	0.116	Likely Benign	Likely Benign										0.053	Likely Benign	-1.04	Neutral	0.025	Benign	0.023	Benign	2.62	Benign	0.70	Tolerated			0.3332	0.5691		1	-1	0.8	-10.04
c.3301C>T	P1101S 2D AIThe SynGAP1 missense variant P1101S is reported in gnomAD (variant ID 6‑33443853‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.968967	Binding	0.457	0.861	0.875								6-33443853-C-T	1	6.52e-7	-3.845	Likely Benign	0.080	Likely Benign	Likely Benign										0.075	Likely Benign	-1.31	Neutral	0.626	Possibly Damaging	0.255	Benign	4.25	Benign	0.07	Tolerated	3.77	5	0.3265	0.5400		-1	1	0.8	-10.04
c.3310C>T	P1104S 2D AIThe SynGAP1 missense variant P1104S is listed in ClinVar (ID 2912797.0) as Benign and is present in gnomAD (variant ID 6‑33443862‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is Likely Benign, and AlphaMissense‑Optimized also reports Benign. Foldetta results are not available. Overall, the majority of computational evidence supports a benign classification, which is consistent with the ClinVar status. Thus, the variant is most likely benign and does not contradict the ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.936162	Disordered	0.954801	Binding	0.440	0.863	0.875					Benign		1	6-33443862-C-T	1	6.54e-7	-2.330	Likely Benign	0.073	Likely Benign	Likely Benign										0.088	Likely Benign	-0.30	Neutral	0.770	Possibly Damaging	0.404	Benign	2.77	Benign	0.10	Tolerated	3.77	5	0.3271	0.5746		-1	1	0.8	-10.04
c.331C>T	P111S 2D AIThe SynGAP1 missense variant P111S 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 also support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the collective predictions strongly suggest that P111S is most likely benign, and this conclusion is not contradicted by any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.650020	Binding	0.438	0.858	0.750											-2.773	Likely Benign	0.307	Likely Benign	Likely Benign										0.033	Likely Benign	-1.03	Neutral	0.131	Benign	0.026	Benign	4.21	Benign	0.29	Tolerated			0.3515	0.4973		1	-1	0.8	-10.04
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.3421C>T	P1141S 2D AIThe SynGAP1 missense variant P1141S is not 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 results are unavailable. Overall, five of the nine evaluated tools predict pathogenicity while four predict benignity, giving a slight majority toward a deleterious effect. Thus, the variant is most likely pathogenic based on current computational predictions, 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.			0.930790	Disordered	0.716087	Binding	0.364	0.852	1.000											-2.574	Likely Benign	0.187	Likely Benign	Likely Benign										0.094	Likely Benign	-3.58	Deleterious	0.856	Possibly Damaging	0.492	Possibly Damaging	0.99	Pathogenic	0.00	Affected			0.3379	0.5566		1	-1	0.8	-10.04
c.3436C>T	P1146S 2D AIThe SynGAP1 missense variant P1146S is reported in ClinVar as “Not submitted” and is present in gnomAD (variant ID 6-33444471-C‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack 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.	Likely Benign		0.919029	Disordered	0.732173	Binding	0.415	0.837	1.000								6-33444471-C-T	2	1.24e-6	-3.045	Likely Benign	0.318	Likely Benign	Likely Benign										0.470	Likely Benign	-3.66	Deleterious	0.945	Possibly Damaging	0.760	Possibly Damaging	5.52	Benign	0.00	Affected	4.32	4	0.3408	0.5186		-1	1	0.8	-10.04
c.3445C>T	P1149S 2D AIThe SynGAP1 missense variant P1149S 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 from 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 for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.786938	Binding	0.424	0.837	0.625											-2.650	Likely Benign	0.184	Likely Benign	Likely Benign										0.067	Likely Benign	0.14	Neutral	0.068	Benign	0.065	Benign	3.18	Benign	0.48	Tolerated			0.3460	0.4826		1	-1	0.8	-10.04
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.364C>T	P122S 2D AIThe SynGAP1 missense variant P122S is catalogued in gnomAD (ID 6‑33432229‑C‑T) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign 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		0.618285	Disordered	0.672358	Binding	0.400	0.887	0.750								6-33432229-C-T	1	6.20e-7	-3.389	Likely Benign	0.098	Likely Benign	Likely Benign										0.091	Likely Benign	-1.13	Neutral	0.036	Benign	0.025	Benign	4.22	Benign	0.31	Tolerated	3.61	5	0.4009	0.4759		-1	1	0.8	-10.04
c.373C>T	P125S 2D AIThe SynGAP1 missense variant P125S is listed in ClinVar (ID 837156.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic predictions come from 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; the Foldetta protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict the ClinVar designation, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.704227	Binding	0.373	0.878	0.625					Uncertain		1				-3.769	Likely Benign	0.238	Likely Benign	Likely Benign										0.121	Likely Benign	-3.57	Deleterious	0.580	Possibly Damaging	0.140	Benign	2.86	Benign	0.02	Affected	3.61	5	0.3408	0.4594		1	-1	0.8	-10.04
c.382C>T	P128S 2D AIThe SynGAP1 missense variant P128S is reported in gnomAD (variant ID 6‑33432247‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant prediction. 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 (majority vote) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.713069	Binding	0.376	0.878	0.625								6-33432247-C-T	1	6.20e-7	-3.234	Likely Benign	0.268	Likely Benign	Likely Benign										0.084	Likely Benign	-1.35	Neutral	0.734	Possibly Damaging	0.243	Benign	4.20	Benign	0.24	Tolerated	3.74	4	0.3893	0.3697		-1	1	0.8	-10.04
c.3832C>T	P1278S 2D AIThe SynGAP1 missense variant P1278S 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 a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.806955	Binding	0.532	0.722	0.750											-4.383	Likely Benign	0.098	Likely Benign	Likely Benign										0.077	Likely Benign	0.28	Neutral	0.004	Benign	0.003	Benign	2.96	Benign	0.35	Tolerated			0.3616	0.3697		1	-1	0.8	-10.04
c.3847C>T	P1283S 2D AIThe SynGAP1 missense variant P1283S is catalogued in gnomAD (ID 6‑33447895‑C‑T) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Therefore, the variant is most likely benign, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.819686	Binding	0.484	0.732	0.875								6-33447895-C-T			-4.289	Likely Benign	0.072	Likely Benign	Likely Benign										0.040	Likely Benign	0.06	Neutral	0.292	Benign	0.110	Benign	2.86	Benign	0.30	Tolerated	3.77	5	0.2837	0.3719		-1	1	0.8	-10.04
c.3853C>T	P1285S 2D AIThe SynGAP1 missense variant P1285S is reported in gnomAD (variant ID 6‑33447901‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The 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, 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 and the high‑accuracy predictions point to a benign impact, and this is not in conflict with ClinVar, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.821643	Binding	0.557	0.759	0.750								6-33447901-C-T	1	6.44e-7	-3.875	Likely Benign	0.086	Likely Benign	Likely Benign										0.035	Likely Benign	-1.27	Neutral	0.802	Possibly Damaging	0.249	Benign	4.34	Benign	0.29	Tolerated	4.32	2	0.2912	0.3319		-1	1	0.8	-10.04
c.3859C>T	P1287S 2D AIThe SynGAP1 missense variant P1287S is catalogued in gnomAD (ID 6‑33447907‑C‑T) but has no ClinVar entry. Across the spectrum of in‑silico predictors, every tool listed—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently scores the variant as benign. No pathogenic predictions are reported. Grouping by agreement, the benign‑predicting tools comprise the entire set, while the pathogenic group is empty. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.813701	Binding	0.538	0.777	0.750								6-33447907-C-T			-3.258	Likely Benign	0.090	Likely Benign	Likely Benign										0.055	Likely Benign	0.70	Neutral	0.004	Benign	0.004	Benign	2.96	Benign	0.96	Tolerated	3.77	5	0.2820	0.3566		-1	1	0.8	-10.04
c.3898C>T	P1300S 2D AIThe SynGAP1 missense variant P1300S is reported in gnomAD (variant ID 6‑33451772‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The 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, 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 P1300S 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		0.788093	Disordered	0.885826	Binding	0.400	0.834	0.875								6-33451772-C-T	1	6.20e-7	-3.476	Likely Benign	0.088	Likely Benign	Likely Benign										0.036	Likely Benign	-0.29	Neutral	0.481	Possibly Damaging	0.157	Benign	2.89	Benign	0.27	Tolerated	3.77	5	0.3242	0.4139		-1	1	0.8	-10.04
c.3901C>T	P1301S 2D AIThe SynGAP1 missense variant P1301S is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports 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		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875											-4.537	Likely Benign	0.071	Likely Benign	Likely Benign										0.087	Likely Benign	1.84	Neutral	0.000	Benign	0.001	Benign	3.29	Benign	0.95	Tolerated			0.2799	0.3436		1	-1	0.8	-10.04
c.3910C>T	P1304S 2D AIThe SynGAP1 missense variant P1304S is reported in gnomAD (ID 6‑33451784‑C‑T) but has no ClinVar entry. Functional prediction tools uniformly classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. 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. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is provided). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.886417	Binding	0.475	0.866	0.875								6-33451784-C-T	1	6.20e-7	-4.103	Likely Benign	0.077	Likely Benign	Likely Benign										0.039	Likely Benign	0.36	Neutral	0.059	Benign	0.041	Benign	3.03	Benign	0.58	Tolerated	3.77	5	0.2900	0.4442		-1	1	0.8	-10.04
c.3919C>T	P1307S 2D AIThe SynGAP1 missense variant P1307S 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		0.798249	Disordered	0.913511	Binding	0.491	0.901	0.875											-3.700	Likely Benign	0.093	Likely Benign	Likely Benign										0.049	Likely Benign	0.45	Neutral	0.239	Benign	0.157	Benign	3.09	Benign	0.48	Tolerated			0.3652	0.4846		1	-1	0.8	-10.04
c.3937C>T	P1313S 2D AIThe SynGAP1 missense variant P1313S is not reported in ClinVar and is absent from gnomAD. In silico prediction tools that assess sequence conservation and structural impact (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all classify the change as benign. No tool in the dataset predicts pathogenicity. The high‑accuracy consensus methods likewise support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign.” Foldetta results are not available, so they do not influence the assessment. Overall, the collective evidence strongly suggests that the variant is most likely benign, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.970301	Binding	0.452	0.902	0.750											-4.279	Likely Benign	0.071	Likely Benign	Likely Benign										0.067	Likely Benign	-0.03	Neutral	0.047	Benign	0.066	Benign	4.33	Benign	0.13	Tolerated			0.3520	0.6153		1	-1	0.8	-10.04
c.3940C>T	P1314S 2D AIThe SynGAP1 missense variant P1314S has no ClinVar entry and is not reported in gnomAD. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the computational evidence strongly 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		0.882776	Disordered	0.971592	Binding	0.467	0.903	0.750											-3.838	Likely Benign	0.081	Likely Benign	Likely Benign										0.046	Likely Benign	0.11	Neutral	0.005	Benign	0.003	Benign	4.22	Benign	0.72	Tolerated			0.3522	0.4751		1	-1	0.8	-10.04
c.3958C>T	P1320S 2D AIThe SynGAP1 missense variant P1320S is listed in ClinVar (ID 469160.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451832‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this is not in conflict with 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		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750					Uncertain		1	6-33451832-C-T	2	1.28e-6	-4.928	Likely Benign	0.073	Likely Benign	Likely Benign										0.097	Likely Benign	-0.69	Neutral	0.980	Probably Damaging	0.968	Probably Damaging	4.25	Benign	0.00	Affected	3.77	5	0.3390	0.5814		1	-1	0.8	-10.04
c.3961C>T	P1321S 2D AIThe SynGAP1 missense variant P1321S is listed in ClinVar (ID 1806027.0) with an “Uncertain” clinical significance and is present in the gnomAD database (gnomAD ID 6‑33451835‑C‑T). All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic prediction. High‑accuracy assessments corroborate this benign trend: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the computational evidence strongly supports 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		0.827927	Disordered	0.933505	Binding	0.463	0.828	0.875					Uncertain		2	6-33451835-C-T	10	6.46e-6	-4.897	Likely Benign	0.077	Likely Benign	Likely Benign										0.049	Likely Benign	0.68	Neutral	0.028	Benign	0.004	Benign	4.27	Benign	0.71	Tolerated	3.77	5	0.3610	0.5190		1	-1	0.8	-10.04																10.1016/j.ajhg.2020.11.011
c.3967C>T	P1323S 2D AIThe SynGAP1 missense variant P1323S 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 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		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875											-6.007	Likely Benign	0.072	Likely Benign	Likely Benign										0.077	Likely Benign	-0.52	Neutral	0.588	Possibly Damaging	0.122	Benign	3.88	Benign	0.00	Affected			0.3758	0.4371		1	-1	0.8	-10.04
c.3970C>T	P1324S 2D AIThe SynGAP1 missense variant P1324S is listed in ClinVar as Benign (ClinVar ID 1137951.0) and is present in gnomAD (ID 6‑33451844‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 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 (majority vote) also benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, which is consistent with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.899181	Binding	0.432	0.793	0.875					Likely Benign		1	6-33451844-C-T	5	3.26e-6	-5.451	Likely Benign	0.068	Likely Benign	Likely Benign										0.049	Likely Benign	0.35	Neutral	0.225	Benign	0.092	Benign	4.33	Benign	0.00	Affected	4.32	1	0.3505	0.4450		1	-1	0.8	-10.04
c.3973C>T	P1325S 2D AIThe SynGAP1 missense variant P1325S is reported in gnomAD (ID 6‑33451847‑C‑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 to be pathogenic. 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 majority 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		0.876521	Disordered	0.893621	Binding	0.439	0.791	0.875								6-33451847-C-T	1	6.43e-7	-5.273	Likely Benign	0.083	Likely Benign	Likely Benign										0.053	Likely Benign	0.29	Neutral	0.010	Benign	0.007	Benign	4.10	Benign	0.00	Affected	4.32	1	0.3657	0.4360		-1	1	0.8	-10.04
c.3976C>T	P1326S 2D AIThe SynGAP1 missense variant P1326S is listed in ClinVar with no submitted interpretation and is present in gnomAD (ID 6‑33451850‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence—including the high‑accuracy tools—supports a benign classification. This conclusion does not contradict the ClinVar status, which currently has no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875								6-33451850-C-T			-5.221	Likely Benign	0.121	Likely Benign	Likely Benign										0.107	Likely Benign	-0.35	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.74	Benign	0.00	Affected	3.77	5	0.3722	0.4563		-1	1	0.8	-10.04
c.3979C>T	P1327S 2D AIThe SynGAP1 missense variant P1327S is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33451853‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875					Uncertain		1	6-33451853-C-T			-4.744	Likely Benign	0.131	Likely Benign	Likely Benign										0.092	Likely Benign	0.28	Neutral	0.980	Probably Damaging	0.857	Possibly Damaging	4.25	Benign	0.71	Tolerated	3.77	5	0.3098	0.4025		1	-1	0.8	-10.04
c.40C>T	P14S 2D AIThe SynGAP1 missense variant P14S is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.471596	Uncertain	0.399	0.909	0.375											-2.352	Likely Benign	0.123	Likely Benign	Likely Benign										0.068	Likely Benign	-0.02	Neutral	0.212	Benign	0.014	Benign	4.23	Benign	0.00	Affected			0.3935	0.5938		1	-1	0.8	-10.04
c.442C>T	P148S 2D AIThe SynGAP1 missense variant P148S is not reported in ClinVar (ClinVar status: not listed) and is present in gnomAD (ID 6‑33432739‑C‑T). 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 (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625								6-33432739-C-T	1	6.33e-7	-3.258	Likely Benign	0.874	Likely Pathogenic	Ambiguous										0.102	Likely Benign	-1.81	Neutral	1.000	Probably Damaging	0.994	Probably Damaging	4.05	Benign	0.39	Tolerated	3.61	5	0.3143	0.4597		-1	1	0.8	-10.04
c.481C>T	P161S 2D AIThe SynGAP1 missense variant P161S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-8.550	Likely Pathogenic	0.945	Likely Pathogenic	Ambiguous										0.085	Likely Benign	-3.63	Deleterious	0.700	Possibly Damaging	0.383	Benign	3.94	Benign	0.00	Affected			0.3628	0.4597		1	-1	0.8	-10.04
c.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.58C>T	P20S 2D AIThe SynGAP1 missense variant P20S is reported in gnomAD (ID 6‑33420322‑C‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from the four benign‑oriented tools). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign effect for P20S, 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		0.529623	Disordered	0.442804	Uncertain	0.448	0.899	0.500								6-33420322-C-T			-3.054	Likely Benign	0.153	Likely Benign	Likely Benign										0.076	Likely Benign	-0.25	Neutral	0.909	Possibly Damaging	0.641	Possibly Damaging	4.30	Benign	0.00	Affected	4.32	1	0.3732	0.5920		-1	1	0.8	-10.04
c.622C>T	P208S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208S missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta. Rosetta’s output is uncertain and therefore not counted as evidence. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to pathogenic, and Foldetta also predicts pathogenic. With no ClinVar annotation to contradict, the overall evidence strongly favors a pathogenic classification for P208S. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-8.363	Likely Pathogenic	0.587	Likely Pathogenic	Likely Benign	2.68	Destabilizing	0.3	1.53	Ambiguous	2.11	Destabilizing	1.21	Destabilizing	0.270	Likely Benign	-6.78	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.79	Benign	0.02	Affected			0.3808	0.4537		1	-1	0.8	-10.04
c.754C>T	P252S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P252S is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM, while the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact. Predictions that are uncertain (FoldX, Rosetta, Foldetta, premPS) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the evidence strongly favors a pathogenic effect for P252S, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-10.926	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.76	Ambiguous	0.1	1.81	Ambiguous	1.29	Ambiguous	0.79	Ambiguous	0.840	Likely Pathogenic	-7.35	Deleterious	0.941	Possibly Damaging	0.531	Possibly Damaging	5.79	Benign	0.05	Affected			0.3508	0.4361		1	-1	0.8	-10.04
c.79C>T	P27S 2D AIThe SynGAP1 missense variant P27S is reported in gnomAD (ID 6‑33423488‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign, and the SGM‑Consensus (derived from the majority of these high‑accuracy predictors) also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign. Foldetta stability analysis is unavailable. Overall, the preponderance of evidence indicates that P27S is most likely benign, and this assessment does not contradict any ClinVar classification, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375								6-33423488-C-T	1	6.20e-7	-2.891	Likely Benign	0.098	Likely Benign	Likely Benign										0.063	Likely Benign	-2.01	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	3.91	Benign	0.00	Affected	4.32	1	0.3916	0.5443		-1	1	0.8	-10.04
c.823C>T	P275S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P275S is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33437728‑C‑T). Prediction tools that agree on a benign effect include REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools—Rosetta, Foldetta, premPS, and ESM1b—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic impact for P275S, 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.		C2	0.059222	Structured	0.353469	Uncertain	0.811	0.208	0.250								6-33437728-C-T	1	6.20e-7	-7.886	In-Between	0.312	Likely Benign	Likely Benign	2.11	Destabilizing	0.3	1.28	Ambiguous	1.70	Ambiguous	0.77	Ambiguous	0.388	Likely Benign	-5.24	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.78	Pathogenic	0.03	Affected	3.38	19	0.3489	0.3339		-1	1	0.8	-10.04
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.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.952C>T	P318S 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318S is present in gnomAD (variant ID 6‑33437857‑C‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a deleterious effect. Pathogenic predictions come from SGM‑Consensus, REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain predictions come from Rosetta and Foldetta. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Taken together, the overwhelming majority of evidence supports a pathogenic classification, and this conclusion is consistent with the absence of a ClinVar record rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000								6-33437857-C-T	1	6.19e-7	-9.954	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	2.22	Destabilizing	0.1	1.71	Ambiguous	1.97	Ambiguous	1.00	Destabilizing	0.626	Likely Pathogenic	-7.05	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.87	Pathogenic	0.03	Affected	3.38	23	0.3692	0.5653		-1	1	0.8	-10.04
c.1045C>A	P349T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P349T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and the SGM‑Consensus score (which is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools with inconclusive results are AlphaMissense‑Default, FoldX, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta as uncertain. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for this variant. 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	C2	0.167087	Structured	0.348607	Uncertain	0.947	0.396	0.000											-9.736	Likely Pathogenic	0.420	Ambiguous	Likely Benign	1.37	Ambiguous	0.1	2.56	Destabilizing	1.97	Ambiguous	0.76	Ambiguous	0.246	Likely Benign	-6.12	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.57	Pathogenic	0.07	Tolerated			0.1615	0.6238		0	-1	0.9	3.99
c.1090C>A	P364T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P364T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Four tools (FoldX, Foldetta, premPS, ESM1b) return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated tools (five benign versus four pathogenic) lean toward a benign classification, and this assessment does not contradict any ClinVar annotation because no ClinVar claim exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.390993	Structured	0.439474	Uncertain	0.942	0.590	0.250											-7.951	In-Between	0.230	Likely Benign	Likely Benign	1.18	Ambiguous	0.6	0.47	Likely Benign	0.83	Ambiguous	0.53	Ambiguous	0.342	Likely Benign	-5.60	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	1.60	Pathogenic	0.09	Tolerated			0.1660	0.5726		0	-1	0.9	3.99
c.1102C>A	P368T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P368T missense variant is not listed in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. FoldX, Rosetta, and Foldetta report uncertain or inconclusive stability changes and are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie (2 benign, 2 pathogenic) and thus inconclusive, and Foldetta remains uncertain. Overall, the predictions are evenly split between benign and pathogenic, providing no definitive classification. The variant’s status does not contradict ClinVar, which has no entry for it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.363090	Structured	0.439989	Uncertain	0.580	0.677	0.250											-5.308	Likely Benign	0.284	Likely Benign	Likely Benign	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.112C>A	P38T 2D AIThe SynGAP1 missense variant P38T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.433285	Uncertain	0.344	0.791	0.375											-3.248	Likely Benign	0.116	Likely Benign	Likely Benign										0.114	Likely Benign	-1.91	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.06	Benign	0.00	Affected			0.1993	0.6717		0	-1	0.9	3.99
c.1192C>A	P398T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P398T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, and SIFT. The remaining tools (Rosetta, Foldetta, premPS, AlphaMissense‑Default) give uncertain results. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta is uncertain. Overall, the majority of high‑confidence predictions lean toward a benign impact, although several other predictors indicate pathogenicity. There is no conflict with ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.436924	Structured	0.401041	Uncertain	0.891	0.525	0.250											-6.670	Likely Benign	0.536	Ambiguous	Likely Benign	2.11	Destabilizing	0.4	1.57	Ambiguous	1.84	Ambiguous	0.78	Ambiguous	0.608	Likely Pathogenic	-5.70	Deleterious	0.816	Possibly Damaging	0.307	Benign	5.51	Benign	0.01	Affected			0.1671	0.6607		0	-1	0.9	3.99
c.1237C>A	P413T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P413T 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 limited to FATHMM, while the remaining tools—SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this view: AlphaMissense‑Optimized classifies the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a Likely Pathogenic verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No predictions are inconclusive or missing. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.332472	Uncertain	0.927	0.201	0.000											-12.851	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	3.22	Destabilizing	0.2	1.87	Ambiguous	2.55	Destabilizing	0.93	Ambiguous	0.554	Likely Pathogenic	-7.37	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.18	Benign	0.01	Affected			0.1663	0.4670		0	-1	0.9	3.99
c.124C>A	P42T 2D AIThe SynGAP1 missense variant P42T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for P42T, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.308712	Structured	0.431487	Uncertain	0.420	0.771	0.375											-3.626	Likely Benign	0.101	Likely Benign	Likely Benign										0.109	Likely Benign	-0.97	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.29	Benign	0.00	Affected			0.1834	0.4896		0	-1	0.9	3.99
c.1309C>A	P437T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P437T 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, FATHMM, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The remaining tools—FoldX, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta yielding an uncertain stability change. Overall, the majority of evidence points toward 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.		GAP	0.175930	Structured	0.306196	Uncertain	0.921	0.298	0.000											-13.011	Likely Pathogenic	0.484	Ambiguous	Likely Benign	1.35	Ambiguous	0.0	-3.46	Stabilizing	-1.06	Ambiguous	0.54	Ambiguous	0.305	Likely Benign	-6.67	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	3.45	Benign	0.01	Affected			0.1659	0.5782		0	-1	0.9	3.99
c.136C>A	P46T 2D AIThe SynGAP1 missense variant P46T is reported in ClinVar as “Not submitted” and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, all of which classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy methods give a consistent benign signal: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Benign,” and Foldetta data are missing. Overall, the majority of reliable predictors and the consensus analysis indicate that P46T is most likely benign, and this conclusion does not contradict the ClinVar status, which contains no pathogenic assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.390993	Structured	0.433588	Uncertain	0.549	0.741	0.375											-4.329	Likely Benign	0.383	Ambiguous	Likely Benign										0.092	Likely Benign	-0.68	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	4.13	Benign	0.00	Affected			0.2194	0.6400		0	-1	0.9	3.99
c.1582C>A	P528T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000											-13.782	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous	2.05	Destabilizing	0.3	1.01	Ambiguous	1.53	Ambiguous	0.66	Ambiguous	0.673	Likely Pathogenic	-7.69	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.49	Pathogenic	0.00	Affected			0.1367	0.4360		0	-1	0.9	3.99
c.1684C>A	P562T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P562T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign outcome; the only uncertain predictions come from Foldetta and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic, while Foldetta remains uncertain. Taken together, the overwhelming majority of computational evidence indicates that P562T is likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022306	Structured	0.023606	Uncertain	0.893	0.200	0.000											-14.747	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	2.62	Destabilizing	0.1	0.51	Ambiguous	1.57	Ambiguous	0.81	Ambiguous	0.697	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.58	Pathogenic	0.00	Affected			0.1892	0.3454		0	-1	0.9	3.99
c.1798C>A	P600T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P600T is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Foldetta, Rosetta, and premPS. Those that predict pathogenicity are REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, while Foldetta indicates a benign effect on protein folding stability. Overall, the majority of computational evidence supports a pathogenic effect for P600T, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009728	Structured	0.162960	Uncertain	0.947	0.147	0.000											-11.945	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	2.61	Destabilizing	0.1	-2.90	Stabilizing	-0.15	Likely Benign	0.24	Likely Benign	0.737	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.34	Pathogenic	0.01	Affected			0.1871	0.4954		0	-1	0.9	3.99
c.1813C>A	P605T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P605T is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts a benign outcome. High‑accuracy methods specifically show pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions or stability results are missing or inconclusive. Based on the unanimous pathogenic predictions and the absence of any ClinVar or gnomAD evidence to the contrary, the variant is most likely pathogenic and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.023087	Structured	0.192737	Uncertain	0.929	0.231	0.000											-11.533	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	2.87	Destabilizing	0.4	2.14	Destabilizing	2.51	Destabilizing	0.72	Ambiguous	0.801	Likely Pathogenic	-7.96	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	0.69	Pathogenic	0.00	Affected			0.1626	0.5228		0	-1	0.9	3.99
c.1843C>A	P615T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P615T is not reported in ClinVar and is absent from gnomAD. Among the evaluated in‑silico predictors, SIFT is the sole tool that predicts a benign effect, whereas the remaining majority—including REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict a pathogenic impact. Predictions from Rosetta, Foldetta, and premPS are uncertain and do not provide definitive evidence. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates it is likely pathogenic, while Foldetta’s stability analysis remains inconclusive. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.236433	Structured	0.179032	Uncertain	0.879	0.255	0.000											-13.764	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	3.02	Destabilizing	0.3	0.95	Ambiguous	1.99	Ambiguous	0.75	Ambiguous	0.823	Likely Pathogenic	-7.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.26	Pathogenic	0.06	Tolerated			0.1602	0.3806		0	-1	0.9	3.99
c.196C>A	P66T 2D AIThe SynGAP1 missense variant P66T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which classifies the variant as Likely Benign. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the Foldetta protein‑folding stability assessment is unavailable. Overall, the balance of evidence leans toward a benign impact, with one high‑accuracy tool (SGM‑Consensus) supporting this view and no ClinVar entry to contradict it. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.394753	Structured	0.474132	Uncertain	0.455	0.762	0.125											-3.373	Likely Benign	0.954	Likely Pathogenic	Ambiguous										0.139	Likely Benign	-1.81	Neutral	0.909	Possibly Damaging	0.641	Possibly Damaging	4.00	Benign	0.00	Affected			0.1747	0.5866		0	-1	0.9	3.99
c.2101C>A	P701T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P701T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the substitution as benign: REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate a tolerated change. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports benign. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive, and FoldX alone is uncertain, so these results are treated as unavailable. Overall, the evidence strongly supports a benign effect for P701T, 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	GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000											-6.920	Likely Benign	0.272	Likely Benign	Likely Benign	1.61	Ambiguous	0.0	0.11	Likely Benign	0.86	Ambiguous	-0.18	Likely Benign	0.144	Likely Benign	-0.43	Neutral	0.084	Benign	0.050	Benign	3.44	Benign	0.70	Tolerated			0.1398	0.4160		0	-1	0.9	3.99
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.2143C>A	P715T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. Two tools, Foldetta and premPS, returned uncertain results. High‑accuracy analyses further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenicity; Foldetta remains inconclusive. 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	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000											-10.501	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign	2.55	Destabilizing	0.1	0.29	Likely Benign	1.42	Ambiguous	0.72	Ambiguous	0.368	Likely Benign	-7.23	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.37	Benign	0.01	Affected			0.1357	0.4072		0	-1	0.9	3.99
c.2182C>A	P728T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P728T has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include only REVEL, while the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. Predictions that are inconclusive or uncertain are FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for P728T, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.632174	Disordered	0.434760	Uncertain	0.725	0.567	0.625											-9.605	Likely Pathogenic	0.863	Likely Pathogenic	Ambiguous	1.06	Ambiguous	0.0	1.27	Ambiguous	1.17	Ambiguous	0.62	Ambiguous	0.298	Likely Benign	-6.21	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1843	0.3917		0	-1	0.9	3.99
c.2200C>A	P734T 2D AIThe SynGAP1 missense variant P734T is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. 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 result available for this variant. Based on the unanimous benign predictions and the lack of any pathogenic 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		0.879233	Disordered	0.411273	Uncertain	0.368	0.721	0.875											-4.469	Likely Benign	0.066	Likely Benign	Likely Benign										0.042	Likely Benign	-2.08	Neutral	0.040	Benign	0.013	Benign	2.78	Benign	0.09	Tolerated			0.1764	0.4076		0	-1	0.9	3.99
c.2221C>A	P741T 2D AIThe SynGAP1 missense variant P741T 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 a “Likely Benign” consensus. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875											-4.626	Likely Benign	0.061	Likely Benign	Likely Benign										0.077	Likely Benign	-0.54	Neutral	0.010	Benign	0.022	Benign	2.86	Benign	0.05	Affected			0.1209	0.5080		0	-1	0.9	3.99
c.2227C>A	P743T 2D AIThe SynGAP1 missense variant P743T 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 flags the variant as pathogenic, creating a single discordant prediction. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus 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 supports a benign classification, 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		0.852992	Disordered	0.526809	Binding	0.317	0.862	0.875											-4.892	Likely Benign	0.061	Likely Benign	Likely Benign										0.050	Likely Benign	-1.11	Neutral	0.454	Possibly Damaging	0.192	Benign	2.75	Benign	0.07	Tolerated			0.1461	0.4750		0	-1	0.9	3.99
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.2251C>A	P751T 2D AIThe SynGAP1 missense variant P751T is not reported 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, 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. Taken together, 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		0.618285	Disordered	0.667683	Binding	0.386	0.866	0.625											-5.111	Likely Benign	0.101	Likely Benign	Likely Benign										0.100	Likely Benign	-1.65	Neutral	0.679	Possibly Damaging	0.348	Benign	2.71	Benign	1.00	Tolerated			0.1613	0.5704		0	-1	0.9	3.99
c.2359C>A	P787T 2D AISynGAP1 missense variant P787T is listed in ClinVar as benign (ClinVar ID 862728.0) and is present in gnomAD (6‑33442911‑C‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions are made by AlphaMissense‑Default, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and the SGM‑Consensus score. The high‑accuracy AlphaMissense‑Optimized result is benign, whereas the SGM‑Consensus, derived from a majority vote of 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 evidence points to a pathogenic effect, which contradicts the ClinVar benign classification. Thus, the variant is most likely pathogenic, contradicting the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750					Likely Benign		1	6-33442911-C-A	17	1.05e-5	-4.813	Likely Benign	0.603	Likely Pathogenic	Likely Benign										0.258	Likely Benign	-4.40	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.46	Pathogenic	0.01	Affected	3.64	6	0.1577	0.5629		0	-1	0.9	3.99
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.2380C>A	P794T 2D AIThe SynGAP1 missense variant P794T is catalogued in gnomAD (ID 6‑33442932‑C‑A) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the dataset predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction. The Foldetta stability analysis is not available for this variant. 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	SH3-binding motif	0.979741	Disordered	0.408951	Uncertain	0.550	0.898	0.875								6-33442932-C-A	1	6.20e-7	-4.838	Likely Benign	0.060	Likely Benign	Likely Benign										0.046	Likely Benign	-0.34	Neutral	0.245	Benign	0.138	Benign	4.25	Benign	0.66	Tolerated	4.07	3	0.1739	0.6207		-1	0	0.9	3.99
c.2383C>A	P795T 2D AIThe SynGAP1 missense variant P795T 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, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity, and the only uncertain result comes from ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. 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	SH3-binding motif	0.972450	Disordered	0.410339	Uncertain	0.457	0.903	0.875											-7.030	In-Between	0.060	Likely Benign	Likely Benign										0.068	Likely Benign	-0.63	Neutral	0.036	Benign	0.026	Benign	4.26	Benign	0.09	Tolerated			0.1713	0.6381		0	-1	0.9	3.99
c.2386C>A	P796T 2D AIThe SynGAP1 P796T missense variant is not reported in ClinVar and has no entry in 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, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign 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	SH3-binding motif	0.936162	Disordered	0.426363	Uncertain	0.427	0.900	0.875											-5.399	Likely Benign	0.062	Likely Benign	Likely Benign										0.082	Likely Benign	-0.01	Neutral	0.494	Possibly Damaging	0.236	Benign	4.26	Benign	0.04	Affected			0.1705	0.4961		0	-1	0.9	3.99
c.2389C>A	P797T 2D AIThe SynGAP1 missense variant P797T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.926919	Disordered	0.449970	Uncertain	0.561	0.902	0.875											-6.554	Likely Benign	0.064	Likely Benign	Likely Benign										0.030	Likely Benign	-0.15	Neutral	0.901	Possibly Damaging	0.708	Possibly Damaging	4.23	Benign	0.24	Tolerated			0.1733	0.5830		0	-1	0.9	3.99
c.2392C>A	P798T 2D AIThe SynGAP1 missense variant P798T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign effect for P798T, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875											-5.926	Likely Benign	0.062	Likely Benign	Likely Benign										0.039	Likely Benign	-0.38	Neutral	0.901	Possibly Damaging	0.534	Possibly Damaging	4.24	Benign	0.00	Affected			0.1293	0.4854		0	-1	0.9	3.99
c.2395C>A	P799T 2D AIThe SynGAP1 missense variant P799T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P799T, 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	SH3-binding motif	0.871313	Disordered	0.537892	Binding	0.400	0.894	0.750											-5.470	Likely Benign	0.063	Likely Benign	Likely Benign										0.033	Likely Benign	-0.82	Neutral	0.951	Possibly Damaging	0.738	Possibly Damaging	4.24	Benign	0.00	Affected			0.1522	0.5257		0	-1	0.9	3.99
c.2431C>A	P811T 2D AIThe SynGAP1 missense variant P811T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect for P811T, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.847064	Binding	0.382	0.910	0.250											-5.329	Likely Benign	0.488	Ambiguous	Likely Benign										0.119	Likely Benign	-1.94	Neutral	0.991	Probably Damaging	0.864	Possibly Damaging	2.77	Benign	0.03	Affected			0.1679	0.6095		0	-1	0.9	3.99
c.2434C>A	P812T 2D AIThe SynGAP1 missense variant P812T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125											-6.956	Likely Benign	0.524	Ambiguous	Likely Benign										0.105	Likely Benign	-1.50	Neutral	0.994	Probably Damaging	0.927	Probably Damaging	2.73	Benign	0.04	Affected			0.1413	0.6114		0	-1	0.9	3.99
c.2452C>A	P818T 2D AIThe SynGAP1 missense variant P818T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.715889	Binding	0.371	0.893	0.625											-6.864	Likely Benign	0.936	Likely Pathogenic	Ambiguous										0.265	Likely Benign	-4.58	Deleterious	0.994	Probably Damaging	0.927	Probably Damaging	2.01	Pathogenic	0.02	Affected			0.1797	0.6453		0	-1	0.9	3.99
c.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.2551C>A	P851T 2D AIThe SynGAP1 missense variant P851T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.526893	Binding	0.347	0.819	0.625											-4.782	Likely Benign	0.060	Likely Benign	Likely Benign										0.146	Likely Benign	-0.70	Neutral	0.999	Probably Damaging	0.995	Probably Damaging	4.24	Benign	0.09	Tolerated			0.1504	0.6691		0	-1	0.9	3.99
c.2653C>A	P885T 2D AIThe SynGAP1 missense variant P885T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.690604	Disordered	0.636133	Binding	0.344	0.917	0.250											-5.152	Likely Benign	0.082	Likely Benign	Likely Benign										0.068	Likely Benign	-1.44	Neutral	0.369	Benign	0.171	Benign	2.78	Benign	0.00	Affected			0.1438	0.6484		0	-1	0.9	3.99
c.2659C>A	P887T 2D AIThe SynGAP1 missense variant P887T 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 change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” while 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 reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.602269	Binding	0.348	0.925	0.500											-4.780	Likely Benign	0.068	Likely Benign	Likely Benign										0.076	Likely Benign	-1.47	Neutral	0.292	Benign	0.110	Benign	2.79	Benign	0.21	Tolerated			0.1228	0.3822		0	-1	0.9	3.99
c.265C>A	P89T 2D AIThe SynGAP1 missense variant P89T has no ClinVar entry and is not reported in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (majority vote) predicts benign. Foldetta stability analysis is unavailable. Overall, the preponderance of evidence leans toward a benign effect, but the presence of a pathogenic prediction from AlphaMissense‑Optimized introduces uncertainty. This assessment does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.545797	Binding	0.316	0.865	0.500											-5.429	Likely Benign	0.979	Likely Pathogenic	Likely Pathogenic										0.105	Likely Benign	-2.49	Neutral	0.588	Possibly Damaging	0.036	Benign	3.74	Benign	0.00	Affected			0.1786	0.4702		0	-1	0.9	3.99
c.2749C>A	P917T 2D AIThe SynGAP1 missense variant P917T 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		0.599170	Disordered	0.863949	Binding	0.314	0.862	0.375											-4.012	Likely Benign	0.082	Likely Benign	Likely Benign										0.044	Likely Benign	-1.68	Neutral	0.139	Benign	0.088	Benign	2.69	Benign	0.00	Affected			0.1445	0.5711		0	-1	0.9	3.99
c.2770C>A	P924T 2D AIThe SynGAP1 missense variant P924T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence indicates that P924T is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250											-6.360	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic										0.400	Likely Benign	-6.03	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1190	0.4009		0	-1	0.9	3.99
c.2788C>A	P930T 2D AIThe SynGAP1 missense variant P930T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL classifies it as benign, whereas the remaining 11 predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts a pathogenic change, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability analysis is available. Overall, the consensus of the majority of tools supports a pathogenic classification, and this is consistent with the absence of any ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.538167	Disordered	0.988036	Binding	0.304	0.855	0.375											-9.558	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic										0.454	Likely Benign	-5.97	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.67	Pathogenic	0.00	Affected			0.1666	0.5593		0	-1	0.9	3.99
c.280C>A	P94T 2D AIThe SynGAP1 missense variant P94T is reported in gnomAD (variant ID 6‑33425888‑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 a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Consequently, the collective evidence indicates that P94T is most likely benign, 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 Benign		0.671169	Disordered	0.570978	Binding	0.350	0.869	0.625								6-33425888-C-A	1	6.20e-7	-4.254	Likely Benign	0.085	Likely Benign	Likely Benign										0.088	Likely Benign	-2.35	Neutral	0.198	Benign	0.015	Benign	4.12	Benign	0.00	Affected	4.32	1	0.1326	0.4789		-1	0	0.9	3.99
c.2815C>A	P939T 2D AIThe SynGAP1 missense variant P939T is not 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. High‑accuracy predictions show AlphaMissense‑Optimized as benign, while the SGM Consensus remains inconclusive and Foldetta is unavailable. Overall, more tools (five) predict pathogenicity than benign (four), suggesting the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.894241	Disordered	0.935841	Binding	0.397	0.897	0.625											-5.739	Likely Benign	0.099	Likely Benign	Likely Benign										0.139	Likely Benign	-3.34	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.22	Pathogenic	0.00	Affected			0.1788	0.5310		0	-1	0.9	3.99
c.2821C>A	P941T 2D AIThe SynGAP1 missense variant P941T is listed in gnomAD (ID 6‑33443373‑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, while only SIFT predicts it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, 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		0.874069	Disordered	0.900790	Binding	0.403	0.906	0.625								6-33443373-C-A	2	1.24e-6	-6.193	Likely Benign	0.065	Likely Benign	Likely Benign										0.033	Likely Benign	0.19	Neutral	0.144	Benign	0.085	Benign	2.77	Benign	0.05	Affected	4.32	4	0.1612	0.5607		-1	0	0.9	3.99
c.2824C>A	P942T 2D AIThe SynGAP1 missense variant P942T is not reported 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 P942T, 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		0.919029	Disordered	0.878102	Binding	0.365	0.915	0.625											-5.745	Likely Benign	0.067	Likely Benign	Likely Benign										0.027	Likely Benign	-1.23	Neutral	0.224	Benign	0.096	Benign	2.49	Pathogenic	0.00	Affected			0.1683	0.5599		0	-1	0.9	3.99
c.2857C>A	P953T 2D AIThe SynGAP1 missense variant P953T is predicted to be benign by all evaluated in silico tools. Consensus predictions from SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classify the variant as Likely Benign. High‑accuracy predictors AlphaMissense‑Optimized also report a benign effect. Other pathogenicity predictors—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM)—uniformly predict benign. No tools predict pathogenicity. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its stability impact remains unknown. The variant is not listed in ClinVar and has no entry in gnomAD, so no population frequency or clinical classification is available. Based on the unanimous benign predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.983019	Disordered	0.920633	Binding	0.403	0.926	0.750											-6.646	Likely Benign	0.072	Likely Benign	Likely Benign										0.075	Likely Benign	-0.80	Neutral	0.009	Benign	0.015	Benign	2.88	Benign	0.24	Tolerated			0.2261	0.6004		0	-1	0.9	3.99
c.2860C>A	P954T 2D AIThe SynGAP1 missense variant P954T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984159	Disordered	0.932268	Binding	0.465	0.926	0.750											-5.657	Likely Benign	0.072	Likely Benign	Likely Benign										0.089	Likely Benign	-0.77	Neutral	0.977	Probably Damaging	0.856	Possibly Damaging	2.79	Benign	0.48	Tolerated			0.1860	0.6324		0	-1	0.9	3.99
c.2911C>A	P971T 2D AIThe SynGAP1 missense variant P971T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625											-5.627	Likely Benign	0.053	Likely Benign	Likely Benign										0.053	Likely Benign	-0.95	Neutral	0.001	Benign	0.003	Benign	3.96	Benign	0.00	Affected			0.1388	0.5888		0	-1	0.9	3.99
c.2914C>A	P972T 2D AIThe SynGAP1 missense variant P972T 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		0.891961	Disordered	0.954150	Binding	0.472	0.904	0.625											-5.144	Likely Benign	0.057	Likely Benign	Likely Benign										0.062	Likely Benign	-1.01	Neutral	0.078	Benign	0.042	Benign	4.29	Benign	0.03	Affected			0.1802	0.5726		0	-1	0.9	3.99
c.2932C>A	P978T 2D AIThe SynGAP1 missense variant P978T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.819762	Disordered	0.975775	Binding	0.425	0.892	0.625											-4.949	Likely Benign	0.217	Likely Benign	Likely Benign										0.125	Likely Benign	-1.23	Neutral	0.818	Possibly Damaging	0.453	Possibly Damaging	4.21	Benign	0.04	Affected			0.1817	0.7089		0	-1	0.9	3.99
c.2977C>A	P993T 2D AIThe SynGAP1 missense variant P993T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.923979	Binding	0.319	0.908	0.750											-4.444	Likely Benign	0.061	Likely Benign	Likely Benign										0.053	Likely Benign	-0.65	Neutral	0.001	Benign	0.010	Benign	4.32	Benign	0.04	Affected			0.1603	0.5789		0	-1	0.9	3.99
c.2983C>A	P995T 2D AIThe SynGAP1 missense variant P995T is not reported 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 further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P995T, 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		0.862302	Disordered	0.935305	Binding	0.338	0.902	0.750											-5.148	Likely Benign	0.058	Likely Benign	Likely Benign										0.034	Likely Benign	-1.15	Neutral	0.224	Benign	0.096	Benign	4.19	Benign	0.00	Affected			0.1467	0.5667		0	-1	0.9	3.99
c.2986C>A	P996T 2D AIThe SynGAP1 missense variant P996T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.775545	Disordered	0.942262	Binding	0.312	0.900	0.750											-5.138	Likely Benign	0.058	Likely Benign	Likely Benign										0.062	Likely Benign	-0.71	Neutral	0.036	Benign	0.039	Benign	4.26	Benign	0.03	Affected			0.1418	0.6163		0	-1	0.9	3.99
c.3034C>A	P1012T 2D AIThe SynGAP1 missense variant P1012T is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.894674	Binding	0.319	0.866	0.625											-4.788	Likely Benign	0.081	Likely Benign	Likely Benign										0.052	Likely Benign	-0.56	Neutral	0.369	Benign	0.171	Benign	2.84	Benign	0.14	Tolerated			0.1399	0.5730		0	-1	0.9	3.99
c.3100C>A	P1034T 2D AIThe SynGAP1 missense variant P1034T is not reported in ClinVar and has no entry in gnomAD, indicating it is not catalogued in these databases. Prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only two tools predict a pathogenic outcome: SIFT and FATHMM. High‑accuracy assessments reinforce the benign consensus: 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 predictions support a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.926919	Disordered	0.991713	Binding	0.343	0.752	0.625											-4.367	Likely Benign	0.285	Likely Benign	Likely Benign										0.026	Likely Benign	-2.00	Neutral	0.126	Benign	0.096	Benign	2.44	Pathogenic	0.03	Affected			0.1518	0.6620		0	-1	0.9	3.99
c.3103C>A	P1035T 2D AIThe SynGAP1 missense variant P1035T is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, 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. AlphaMissense‑Default remains uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence from AlphaMissense‑Optimized and the SGM‑Consensus both support a benign classification, while the absence of a Foldetta result does not alter this view. Overall, the majority of predictions indicate a benign effect, 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		0.945666	Disordered	0.989572	Binding	0.300	0.756	0.625					Uncertain		1				-4.447	Likely Benign	0.426	Ambiguous	Likely Benign										0.087	Likely Benign	-0.96	Neutral	0.901	Possibly Damaging	0.537	Possibly Damaging	2.72	Benign	0.23	Tolerated	3.77	5	0.1628	0.7220		0	-1	0.9	3.99
c.3121C>A	P1041T 2D AIThe SynGAP1 missense variant P1041T 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		0.962114	Disordered	0.967463	Binding	0.345	0.833	0.625											-5.009	Likely Benign	0.187	Likely Benign	Likely Benign										0.361	Likely Benign	-2.45	Neutral	0.051	Benign	0.025	Benign	5.50	Benign	0.10	Tolerated			0.1632	0.6699		0	-1	0.9	3.99
c.3130C>A	P1044T 2D AIThe SynGAP1 missense variant P1044T is catalogued in gnomAD (ID 6‑33443682‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.979741	Disordered	0.952126	Binding	0.331	0.855	0.750								6-33443682-C-A	1	6.20e-7	-4.605	Likely Benign	0.075	Likely Benign	Likely Benign										0.372	Likely Benign	-1.02	Neutral	0.126	Benign	0.096	Benign	5.53	Benign	0.17	Tolerated	3.77	5	0.1681	0.6860		-1	0	0.9	3.99
c.3136C>A	P1046T 2D AIThe SynGAP1 missense variant P1046T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable 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		0.970265	Disordered	0.942366	Binding	0.364	0.898	0.750											-5.249	Likely Benign	0.068	Likely Benign	Likely Benign										0.052	Likely Benign	-1.18	Neutral	0.411	Benign	0.131	Benign	2.37	Pathogenic	0.21	Tolerated			0.1430	0.5934		0	-1	0.9	3.99
c.3145C>A	P1049T 2D AIThe SynGAP1 missense variant P1049T 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 P1049T 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		0.978316	Disordered	0.917915	Binding	0.428	0.920	0.750											-5.100	Likely Benign	0.056	Likely Benign	Likely Benign										0.088	Likely Benign	-1.18	Neutral	0.519	Possibly Damaging	0.222	Benign	2.74	Benign	0.02	Affected			0.1791	0.5514		0	-1	0.9	3.99
c.3193C>A	P1065T 2D AIThe SynGAP1 missense variant P1065T is 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 classification. There is no ClinVar status to contradict this assessment, so the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.979741	Disordered	0.959518	Binding	0.424	0.917	0.875											-5.392	Likely Benign	0.074	Likely Benign	Likely Benign										0.062	Likely Benign	-1.23	Neutral	0.770	Possibly Damaging	0.481	Possibly Damaging	2.04	Pathogenic	0.00	Affected			0.1577	0.6788		0	-1	0.9	3.99
c.3196C>A	P1066T 2D AIThe SynGAP1 missense variant P1066T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: 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 any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.967676	Disordered	0.968838	Binding	0.403	0.913	0.875											-5.973	Likely Benign	0.082	Likely Benign	Likely Benign										0.167	Likely Benign	-2.61	Deleterious	0.996	Probably Damaging	0.928	Probably Damaging	2.66	Benign	0.00	Affected			0.1652	0.7240		0	-1	0.9	3.99
c.3199C>A	P1067T 2D AIThe SynGAP1 missense variant P1067T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 HumDiv and SIFT predict pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.966441	Disordered	0.975099	Binding	0.459	0.907	0.875											-4.898	Likely Benign	0.084	Likely Benign	Likely Benign										0.062	Likely Benign	-1.94	Neutral	0.827	Possibly Damaging	0.375	Benign	2.79	Benign	0.04	Affected			0.1449	0.6132		0	-1	0.9	3.99
c.3250C>A	P1084T 2D AIThe SynGAP1 missense variant P1084T is reported in ClinVar as “Not submitted” and is present in gnomAD (ID 6‑33443802‑C‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.842060	Disordered	0.979020	Binding	0.348	0.889	1.000								6-33443802-C-A			-4.665	Likely Benign	0.089	Likely Benign	Likely Benign										0.127	Likely Benign	-2.14	Neutral	0.025	Benign	0.012	Benign	4.11	Benign	0.01	Affected	3.77	5	0.1546	0.6793		-1	0	0.9	3.99
c.3256C>A	P1086T 2D AIThe SynGAP1 missense variant P1086T is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑A). 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 results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. The variant is most likely pathogenic based on the available computational evidence, 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-A			-4.181	Likely Benign	0.568	Likely Pathogenic	Likely Benign										0.229	Likely Benign	-2.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.75	Benign	0.00	Affected	3.77	5	0.1343	0.5848		-1	0	0.9	3.99
c.3283C>A	P1095T 2D AIThe SynGAP1 missense variant P1095T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of the available predictions 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		0.922952	Disordered	0.979251	Binding	0.387	0.870	1.000											-4.706	Likely Benign	0.195	Likely Benign	Likely Benign										0.108	Likely Benign	-1.42	Neutral	0.872	Possibly Damaging	0.399	Benign	2.77	Benign	0.13	Tolerated			0.1685	0.6677		0	-1	0.9	3.99
c.3289C>A	P1097T 2D AIThe SynGAP1 missense variant P1097T 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 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, is not available for this variant. Overall, the computational evidence strongly supports a benign impact, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.974957	Binding	0.384	0.858	1.000											-5.000	Likely Benign	0.097	Likely Benign	Likely Benign										0.110	Likely Benign	-1.38	Neutral	0.009	Benign	0.013	Benign	2.61	Benign	0.21	Tolerated			0.1751	0.6567		0	-1	0.9	3.99
c.3301C>A	P1101T 2D AIThe SynGAP1 missense variant P1101T is not reported 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		0.874069	Disordered	0.968967	Binding	0.457	0.861	0.875											-4.161	Likely Benign	0.070	Likely Benign	Likely Benign										0.126	Likely Benign	-1.60	Neutral	0.115	Benign	0.031	Benign	4.22	Benign	0.04	Affected			0.1729	0.5860		0	-1	0.9	3.99
c.3310C>A	P1104T 2D AIThe SynGAP1 missense variant P1104T is reported in gnomAD (variant ID 6‑33443862‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. No Foldetta stability analysis is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign impact, and this assessment 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		0.936162	Disordered	0.954801	Binding	0.440	0.863	0.875								6-33443862-C-A			-3.995	Likely Benign	0.070	Likely Benign	Likely Benign										0.094	Likely Benign	-0.14	Neutral	0.770	Possibly Damaging	0.481	Possibly Damaging	2.76	Benign	0.09	Tolerated	3.77	5	0.1549	0.6700		-1	0	0.9	3.99
c.331C>A	P111T 2D AIThe SynGAP1 missense variant P111T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.650020	Binding	0.438	0.858	0.750											-2.800	Likely Benign	0.305	Likely Benign	Likely Benign										0.061	Likely Benign	-1.44	Neutral	0.421	Benign	0.050	Benign	4.11	Benign	0.02	Affected			0.1650	0.5402		0	-1	0.9	3.99
c.3391C>A	P1131T 2D AIThe SynGAP1 missense variant P1131T is not 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, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the 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	0.855155	Binding	0.360	0.899	0.750											-4.766	Likely Benign	0.219	Likely Benign	Likely Benign										0.313	Likely Benign	-2.93	Deleterious	0.245	Benign	0.096	Benign	5.30	Benign	0.00	Affected			0.1353	0.6315		0	-1	0.9	3.99
c.3421C>A	P1141T 2D AIThe SynGAP1 missense variant P1141T is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). 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, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs. two pathogenic). High‑accuracy methods give AlphaMissense‑Optimized a benign prediction; the SGM Consensus remains inconclusive, and Foldetta (combining FoldX‑MD and Rosetta) has no available result. Overall, the balance of evidence, particularly the benign call from the high‑accuracy AlphaMissense‑Optimized model, suggests that the variant is most likely benign, and this assessment does not contradict the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.716087	Binding	0.364	0.852	1.000											-4.090	Likely Benign	0.176	Likely Benign	Likely Benign										0.106	Likely Benign	-3.85	Deleterious	0.856	Possibly Damaging	0.723	Possibly Damaging	0.98	Pathogenic	0.00	Affected			0.1594	0.6145		0	-1	0.9	3.99
c.3436C>A	P1146T 2D AIThe SynGAP1 missense variant P1146T is not 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 polyPhen‑2 HumVar, as well as the SGM‑Consensus call of “Likely Benign.” In contrast, PROVEAN, polyPhen‑2 HumDiv, and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Foldetta results are not available. Overall, the majority of evidence points to a benign effect for P1146T, 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		0.919029	Disordered	0.732173	Binding	0.415	0.837	1.000											-3.494	Likely Benign	0.272	Likely Benign	Likely Benign										0.454	Likely Benign	-4.11	Deleterious	0.573	Possibly Damaging	0.334	Benign	5.51	Benign	0.00	Affected			0.1478	0.5789		0	-1	0.9	3.99
c.3445C>A	P1149T 2D AIThe SynGAP1 missense variant P1149T 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. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for P1149T, 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		0.762850	Disordered	0.786938	Binding	0.424	0.837	0.625											-3.317	Likely Benign	0.185	Likely Benign	Likely Benign										0.092	Likely Benign	-0.98	Neutral	0.649	Possibly Damaging	0.355	Benign	2.71	Benign	0.04	Affected			0.1755	0.5537		0	-1	0.9	3.99
c.3484C>A	P1162T 2D AIThe SynGAP1 missense variant P1162T is not reported 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 the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375											-3.466	Likely Benign	0.879	Likely Pathogenic	Ambiguous										0.171	Likely Benign	-2.15	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	2.71	Benign	0.22	Tolerated			0.1395	0.6097		0	-1	0.9	3.99
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.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.382C>A	P128T 2D AIThe SynGAP1 missense variant P128T is listed in ClinVar with an “Uncertain” status (ClinVar ID 2801315.0) and is present in gnomAD (ID 6‑33432247‑C‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.497853	Structured	0.713069	Binding	0.376	0.878	0.625					Uncertain		1	6-33432247-C-A	1	6.20e-7	-4.217	Likely Benign	0.267	Likely Benign	Likely Benign										0.075	Likely Benign	-0.96	Neutral	0.952	Possibly Damaging	0.500	Possibly Damaging	4.19	Benign	0.35	Tolerated	3.74	4	0.2023	0.4053		-1	0	0.9	3.99
c.3832C>A	P1278T 2D AIThe SynGAP1 missense variant P1278T is catalogued in gnomAD (ID 6‑33447880‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, and this assessment does not contradict any ClinVar classification. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.806955	Binding	0.532	0.722	0.750								6-33447880-C-A			-5.505	Likely Benign	0.095	Likely Benign	Likely Benign										0.064	Likely Benign	-0.60	Neutral	0.059	Benign	0.026	Benign	2.73	Benign	0.11	Tolerated	3.77	5	0.1825	0.4053		-1	0	0.9	3.99
c.3847C>A	P1283T 2D AIThe SynGAP1 missense variant P1283T is catalogued in gnomAD (ID 6‑33447895‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Therefore, 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		0.762850	Disordered	0.819686	Binding	0.484	0.732	0.875								6-33447895-C-A			-4.781	Likely Benign	0.064	Likely Benign	Likely Benign										0.071	Likely Benign	-0.45	Neutral	0.451	Benign	0.193	Benign	2.76	Benign	0.11	Tolerated	3.77	5	0.1269	0.3784		-1	0	0.9	3.99
c.3853C>A	P1285T 2D AIThe SynGAP1 missense variant P1285T is catalogued in gnomAD (ID 6‑33447901‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign outcome: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts 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 that integrates FoldX‑MD and Rosetta outputs, has no reported result for this variant, so its status is unavailable. Overall, the computational evidence overwhelmingly supports a benign effect, 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		0.834292	Disordered	0.821643	Binding	0.557	0.759	0.750								6-33447901-C-A			-4.230	Likely Benign	0.078	Likely Benign	Likely Benign										0.047	Likely Benign	-0.35	Neutral	0.451	Benign	0.193	Benign	4.33	Benign	0.40	Tolerated	4.32	2	0.1496	0.3556		-1	0	0.9	3.99
c.3859C>A	P1287T 2D AIThe SynGAP1 missense variant P1287T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33447907‑C‑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 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		0.827927	Disordered	0.813701	Binding	0.538	0.777	0.750					Uncertain		1	6-33447907-C-A			-3.940	Likely Benign	0.077	Likely Benign	Likely Benign										0.044	Likely Benign	-0.22	Neutral	0.126	Benign	0.041	Benign	2.78	Benign	0.04	Affected	3.77	5	0.1189	0.3995		-1	0	0.9	3.99
c.3898C>A	P1300T 2D AIThe SynGAP1 missense variant P1300T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification, 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		0.788093	Disordered	0.885826	Binding	0.400	0.834	0.875											-4.522	Likely Benign	0.093	Likely Benign	Likely Benign										0.070	Likely Benign	-0.64	Neutral	0.649	Possibly Damaging	0.266	Benign	2.87	Benign	0.21	Tolerated			0.1546	0.4729		0	-1	0.9	3.99
c.3901C>A	P1301T 2D AIThe SynGAP1 missense variant P1301T is reported in gnomAD (ID 6‑33451775‑C‑A) and has no ClinVar entry. All evaluated in silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the consensus of all available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875								6-33451775-C-A	1	6.20e-7	-4.945	Likely Benign	0.075	Likely Benign	Likely Benign										0.090	Likely Benign	0.34	Neutral	0.000	Benign	0.001	Benign	2.87	Benign	0.47	Tolerated	3.77	5	0.1255	0.3312		-1	0	0.9	3.99
c.3910C>A	P1304T 2D AIThe SynGAP1 missense variant P1304T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.886417	Binding	0.475	0.866	0.875											-4.454	Likely Benign	0.072	Likely Benign	Likely Benign										0.091	Likely Benign	-0.42	Neutral	0.001	Benign	0.002	Benign	2.86	Benign	0.14	Tolerated			0.1571	0.4914		0	-1	0.9	3.99
c.3919C>A	P1307T 2D AIThe SynGAP1 missense variant P1307T 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 predicts 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) indicates a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the consensus of all available predictions strongly suggests that P1307T is most likely benign, and this conclusion is consistent with the lack of ClinVar pathogenic annotation. 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											-4.262	Likely Benign	0.093	Likely Benign	Likely Benign										0.072	Likely Benign	0.20	Neutral	0.386	Benign	0.266	Benign	3.07	Benign	0.60	Tolerated			0.1732	0.5436		0	-1	0.9	3.99
c.3937C>A	P1313T 2D AIThe SynGAP1 missense variant P1313T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is consistent with the lack of a ClinVar classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.970301	Binding	0.452	0.902	0.750											-4.666	Likely Benign	0.071	Likely Benign	Likely Benign										0.149	Likely Benign	0.03	Neutral	0.000	Benign	0.002	Benign	4.26	Benign	0.14	Tolerated			0.1889	0.7040		0	-1	0.9	3.99
c.3940C>A	P1314T 2D AIThe SynGAP1 missense variant P1314T is present in gnomAD (ID 6‑33451814‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect. Benign predictions come from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status remains unavailable. Overall, the computational evidence overwhelmingly supports a benign impact, and this is consistent with the absence of a ClinVar pathogenic classification. Thus, the variant is most likely benign, and this is consistent with the lack of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.971592	Binding	0.467	0.903	0.750								6-33451814-C-A			-4.083	Likely Benign	0.096	Likely Benign	Likely Benign										0.066	Likely Benign	1.26	Neutral	0.061	Benign	0.045	Benign	4.32	Benign	0.97	Tolerated	3.77	5	0.1791	0.5626		-1	0	0.9	3.99
c.3958C>A	P1320T 2D AIThe SynGAP1 missense variant P1320T is reported in gnomAD (variant ID 6‑33451832‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: the majority (REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a benign effect, while a minority (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT) predict pathogenicity. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.946297	Binding	0.510	0.833	0.750								6-33451832-C-A	1	6.42e-7	-5.355	Likely Benign	0.077	Likely Benign	Likely Benign										0.091	Likely Benign	-0.86	Neutral	0.994	Probably Damaging	0.981	Probably Damaging	4.21	Benign	0.00	Affected	3.77	5	0.1787	0.6392		-1	0	0.9	3.99
c.3961C>A	P1321T 2D AIThe SynGAP1 missense variant P1321T is catalogued in gnomAD (ID 6‑33451835‑C‑A) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the absence of a ClinVar pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.933505	Binding	0.463	0.828	0.875								6-33451835-C-A			-4.946	Likely Benign	0.074	Likely Benign	Likely Benign										0.058	Likely Benign	1.07	Neutral	0.115	Benign	0.012	Benign	4.25	Benign	1.00	Tolerated	3.77	5	0.2016	0.5901		-1	0	0.9	3.99
c.3967C>A	P1323T 2D AIThe SynGAP1 missense variant P1323T is reported in gnomAD (ID 6‑33451841‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as tolerated or benign. Only two algorithms—polyPhen‑2 HumDiv and SIFT—suggest a damaging impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta results are not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with any ClinVar classification, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.901269	Disordered	0.907659	Binding	0.489	0.814	0.875								6-33451841-C-A			-6.296	Likely Benign	0.073	Likely Benign	Likely Benign										0.064	Likely Benign	-0.37	Neutral	0.588	Possibly Damaging	0.227	Benign	3.95	Benign	0.00	Affected	4.32	1	0.1988	0.5161		-1	0	0.9	3.99
c.3970C>A	P1324T 2D AIThe SynGAP1 missense variant P1324T is listed in gnomAD (ID 6‑33451844‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the available predictions points to a benign effect, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.899181	Binding	0.432	0.793	0.875								6-33451844-C-A			-5.289	Likely Benign	0.077	Likely Benign	Likely Benign										0.072	Likely Benign	0.95	Neutral	0.588	Possibly Damaging	0.175	Benign	4.43	Benign	0.00	Affected	4.32	1	0.1863	0.4761		-1	0	0.9	3.99
c.3973C>A	P1325T 2D AIThe SynGAP1 missense variant P1325T is reported in gnomAD (ID 6‑33451847‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign effect for P1325T, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.893621	Binding	0.439	0.791	0.875								6-33451847-C-A			-5.880	Likely Benign	0.083	Likely Benign	Likely Benign										0.135	Likely Benign	-0.14	Neutral	0.000	Benign	0.001	Benign	4.07	Benign	0.00	Affected	4.32	1	0.1814	0.5150		-1	0	0.9	3.99
c.3976C>A	P1326T 2D AIThe SynGAP1 missense variant P1326T is reported in gnomAD (ID 6‑33451850‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also reports a benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority of the same four high‑accuracy tools) is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates that P1326T is most likely benign, and this assessment does not contradict any ClinVar classification because no ClinVar variant is listed. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.948786	Disordered	0.887377	Binding	0.393	0.782	0.875								6-33451850-C-A			-5.755	Likely Benign	0.117	Likely Benign	Likely Benign										0.135	Likely Benign	-0.26	Neutral	0.999	Probably Damaging	0.992	Probably Damaging	3.71	Benign	0.00	Affected	3.77	5	0.1955	0.5517		-1	0	0.9	3.99
c.3979C>A	P1327T 2D AIThe SynGAP1 missense variant P1327T is reported in gnomAD (ID 6‑33451853‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875								6-33451853-C-A			-5.263	Likely Benign	0.150	Likely Benign	Likely Benign										0.144	Likely Benign	1.20	Neutral	0.994	Probably Damaging	0.908	Possibly Damaging	4.51	Benign	1.00	Tolerated	3.77	5	0.1386	0.4779		-1	0	0.9	3.99
c.40C>A	P14T 2D AIThe SynGAP1 missense variant P14T is reported in gnomAD (ID 6‑33420304‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also reports likely benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for P14T, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.471596	Uncertain	0.399	0.909	0.375								6-33420304-C-A			-3.261	Likely Benign	0.150	Likely Benign	Likely Benign										0.078	Likely Benign	-0.27	Neutral	0.212	Benign	0.014	Benign	4.20	Benign	0.00	Affected	4.32	1	0.1912	0.6658		-1	0	0.9	3.99
c.442C>A	P148T 2D AIThe SynGAP1 missense variant P148T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this conclusion, so the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.500109	Binding	0.372	0.837	0.625											-4.762	Likely Benign	0.781	Likely Pathogenic	Likely Benign										0.108	Likely Benign	-1.39	Neutral	1.000	Probably Damaging	0.994	Probably Damaging	4.03	Benign	0.15	Tolerated			0.1698	0.4850		0	-1	0.9	3.99
c.481C>A	P161T 2D AIThe SynGAP1 missense variant P161T has no ClinVar entry and is not reported in gnomAD. Computational predictors fall into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy tools further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus also indicates Likely Pathogenic. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.509769	Disordered	0.520000	Binding	0.256	0.713	0.375											-8.759	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic										0.153	Likely Benign	-3.77	Deleterious	0.535	Possibly Damaging	0.310	Benign	3.92	Benign	0.00	Affected			0.1891	0.5038		0	-1	0.9	3.99
c.565C>A	P189T 2D AISynGAP1 missense variant P189T is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority‑vote method) reports it as likely pathogenic; Foldetta 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		0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250											-8.622	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic										0.265	Likely Benign	-5.26	Deleterious	0.384	Benign	0.177	Benign	4.05	Benign	0.05	Affected			0.1603	0.6392		0	-1	0.9	3.99
c.58C>A	P20T 2D AIThe SynGAP1 missense variant P20T is reported in gnomAD (ID 6‑33420322‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT each predict pathogenic. High‑accuracy assessments reinforce the benign view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence, including the high‑accuracy tools, points to the variant being 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		0.529623	Disordered	0.442804	Uncertain	0.448	0.899	0.500								6-33420322-C-A			-3.258	Likely Benign	0.223	Likely Benign	Likely Benign										0.065	Likely Benign	-0.50	Neutral	0.909	Possibly Damaging	0.641	Possibly Damaging	4.28	Benign	0.00	Affected	4.32	1	0.1781	0.6640		-1	0	0.9	3.99
c.622C>A	P208T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P208T missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta; premPS and Rosetta are uncertain. High‑accuracy methods give a consistent pathogenic signal: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta also predicts pathogenic. With the majority of tools, including the high‑accuracy ones, indicating pathogenicity, the variant is most likely pathogenic. This assessment does not contradict ClinVar status, as the variant is currently unreported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.271506	Structured	0.399506	Uncertain	0.864	0.345	0.125											-9.016	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign	3.20	Destabilizing	0.5	1.27	Ambiguous	2.24	Destabilizing	0.94	Ambiguous	0.270	Likely Benign	-6.80	Deleterious	1.000	Probably Damaging	0.994	Probably Damaging	3.76	Benign	0.01	Affected			0.1857	0.5197		0	-1	0.9	3.99
c.754C>A	P252T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P252T is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include polyPhen‑2 HumDiv, polyPhen‑2 HumVar and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized and the SGM‑Consensus score (Likely Pathogenic). Four tools (FoldX, Rosetta, Foldetta, premPS) give uncertain results and are treated as unavailable. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts pathogenic; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; Foldetta’s stability assessment is uncertain. Overall, the majority of evidence points to a pathogenic effect, and this is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.461924	Structured	0.211606	Uncertain	0.753	0.304	0.250											-11.824	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	1.24	Ambiguous	0.1	1.89	Ambiguous	1.57	Ambiguous	0.71	Ambiguous	0.828	Likely Pathogenic	-7.35	Deleterious	0.384	Benign	0.177	Benign	5.78	Benign	0.01	Affected			0.1514	0.4842		0	-1	0.9	3.99
c.79C>A	P27T 2D AIThe SynGAP1 missense variant P27T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence, including high‑accuracy tools, points to a benign effect for P27T, 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		0.517562	Disordered	0.437871	Uncertain	0.430	0.881	0.375											-3.612	Likely Benign	0.103	Likely Benign	Likely Benign										0.106	Likely Benign	-2.07	Neutral	0.909	Possibly Damaging	0.901	Possibly Damaging	3.85	Benign	0.00	Affected			0.2430	0.5923		0	-1	0.9	3.99
c.823C>A	P275T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P275T is reported in gnomAD (ID 6‑33437728‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions arise from FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The high‑accuracy AlphaMissense‑Optimized score is benign, whereas the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain and therefore not considered evidence. No other tools provide conclusive results. Overall, the majority of predictions, including the SGM‑Consensus, indicate a pathogenic effect, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.059222	Structured	0.353469	Uncertain	0.811	0.208	0.250								6-33437728-C-A	3	1.86e-6	-8.708	Likely Pathogenic	0.309	Likely Benign	Likely Benign	2.44	Destabilizing	0.3	1.15	Ambiguous	1.80	Ambiguous	0.69	Ambiguous	0.425	Likely Benign	-5.38	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.75	Pathogenic	0.01	Affected	3.38	19	0.1808	0.4000		-1	0	0.9	3.99
c.826C>A	P276T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P276T 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, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Uncertain or inconclusive results come from Rosetta, Foldetta, and premPS. High‑accuracy methods give the following: AlphaMissense‑Optimized predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign, two pathogenic), and Foldetta is uncertain. Overall, the majority of tools (six pathogenic vs. four benign) indicate a pathogenic impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.037156	Structured	0.338937	Uncertain	0.724	0.230	0.250											-5.793	Likely Benign	0.146	Likely Benign	Likely Benign	2.61	Destabilizing	0.1	0.75	Ambiguous	1.68	Ambiguous	0.63	Ambiguous	0.293	Likely Benign	-3.53	Deleterious	0.961	Probably Damaging	0.721	Possibly Damaging	1.87	Pathogenic	0.03	Affected			0.1601	0.4676		0	-1	0.9	3.99
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.952C>A	P318T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P318T is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly favor a deleterious effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict pathogenic or likely pathogenic. No tool in the dataset predicts a benign outcome; the only inconclusive results come from Rosetta, Foldetta, and premPS, which are treated as unavailable evidence. High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta is uncertain. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000											-10.759	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	2.03	Destabilizing	0.2	1.54	Ambiguous	1.79	Ambiguous	0.84	Ambiguous	0.680	Likely Pathogenic	-7.09	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.84	Pathogenic	0.01	Affected			0.1583	0.6044		0	-1	0.9	3.99
c.1072T>C	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.290	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1074C>A	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results are reported for Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable due to inconclusiveness. Overall, the majority of available evidence points to a pathogenic impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1074C>G	F358L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F358L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Uncertain or inconclusive results come from Rosetta, Foldetta, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts pathogenic, while Foldetta’s stability prediction is unavailable. Overall, the majority of reliable tools predict a pathogenic impact for F358L. This conclusion does not contradict ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.222385	Structured	0.407113	Uncertain	0.912	0.441	0.250											-7.865	In-Between	0.964	Likely Pathogenic	Likely Pathogenic	0.18	Likely Benign	0.1	1.62	Ambiguous	0.90	Ambiguous	0.97	Ambiguous	0.215	Likely Benign	-4.21	Deleterious	0.982	Probably Damaging	0.952	Probably Damaging	4.12	Benign	0.22	Tolerated			0.2555	0.3602		2	0	1.0	-34.02
c.1202G>A	R401Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438107‑G‑A). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of evaluated algorithms (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic impact. Uncertain results are reported by FoldX, Rosetta, and Foldetta. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely pathogenic, and Foldetta’s stability prediction is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that R401Q is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000					Uncertain		2	6-33438107-G-A			-11.213	Likely Pathogenic	0.969	Likely Pathogenic	Likely Pathogenic	0.96	Ambiguous	0.1	1.50	Ambiguous	1.23	Ambiguous	1.20	Destabilizing	0.780	Likely Pathogenic	-3.69	Deleterious	0.999	Probably Damaging	0.978	Probably Damaging	5.47	Benign	0.04	Affected	3.38	27	0.3234	0.2269		1	1	1.0	-28.06
c.1258T>C	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise the SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated predictors (six pathogenic vs. five benign) indicate that F420L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	0.262	Likely Benign	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	0.2053	0.3016		2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1260T>A	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Tools that predict a pathogenic effect comprise the SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability results and are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta as uncertain. Overall, the majority of evaluated predictors (six pathogenic vs. five benign) indicate that F420L is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000											-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	0.146	Likely Benign	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	0.2053	0.3016		2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1260T>G	F420L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F420L is listed in ClinVar (ID 1397885.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Those that predict a pathogenic effect comprise premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Stability‑based methods (FoldX, Rosetta, Foldetta) yield inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus also as pathogenic, while Foldetta remains uncertain. Overall, the majority of evidence points toward a pathogenic impact, which does not contradict the ClinVar “Uncertain” status but suggests the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.384475	Uncertain	0.974	0.255	0.000					Uncertain		1				-8.432	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	1.76	Ambiguous	0.0	1.41	Ambiguous	1.59	Ambiguous	1.04	Destabilizing	0.146	Likely Benign	-5.39	Deleterious	0.009	Benign	0.005	Benign	4.22	Benign	0.39	Tolerated	3.37	29	0.2053	0.3016		2	0	1.0	-34.02	231.1	13.2	0.0	0.0	-0.1	0.0						X		Potentially Benign	In the WT, the phenyl ring of the Phe420 side chain, located on an α helix (res. Met414-Glu436), packs against hydrophobic residues in the interhelix area of the GAP domain (e.g., Leu689, Leu714, Leu717, Leu718). In the variant simulations, the iso-butyl side chain of Leu420 also packs into the hydrophobic inter-helix niche, but due to its smaller size, the resulting steric interactions are not as favorable as with phenylalanine. In short, the residue swap does not cause severe effects on the protein structure based on the variant simulations.
c.1286G>A	R429Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429Q is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438191‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b, while premPS is inconclusive. The high‑accuracy consensus (SGM Consensus) – a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN – yields a “Likely Benign” result. AlphaMissense‑Optimized itself predicts benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Taken together, the preponderance of evidence points to a benign impact for R429Q, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000					Uncertain		2	6-33438191-G-A	10	6.20e-6	-8.227	Likely Pathogenic	0.143	Likely Benign	Likely Benign	0.45	Likely Benign	0.1	0.36	Likely Benign	0.41	Likely Benign	0.98	Ambiguous	0.156	Likely Benign	-1.25	Neutral	1.000	Probably Damaging	0.979	Probably Damaging	3.47	Benign	0.58	Tolerated	3.38	25	0.2518	0.1985		1	1	1.0	-28.06	235.8	59.5	0.0	0.0	-0.3	0.4		X						Potentially Pathogenic	The guanidinium group of the Arg429 side chain, located in an α helix (res. Met414-Glu436), either forms a salt bridge with the carboxylate group of an acidic residue (Asp474, Asp467) or an H-bond with the hydroxyl group of Ser471 in an opposing α helix (res. Ala461-Phe476). In the variant simulations, Gln429 cannot form ionic interactions with the acidic residues; however, the carboxamide group can form multiple H-bonds. The H-bonding coordination of the Asn429 side chain varied between the replica simulations. In one simulation, three H-bonds were formed simultaneously with the Asp467 side chain, the backbone carbonyl group of Asn426, and the amide group of Met430 at the end of the same α helix. The residue swap could affect the tertiary structure assembly during folding due to weaker bond formation, but no large-scale negative effects were seen during the simulations.
c.1390T>C	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.435	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>A	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.1392C>G	F464L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F464L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, SIFT, and FATHMM, whereas pathogenic predictions are returned by SGM‑Consensus (Likely Pathogenic), premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive stability assessments. High‑accuracy methods specifically indicate pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta’s combined FoldX‑MD and Rosetta output is uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this assessment does not conflict with any ClinVar annotation because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.268042	Structured	0.313424	Uncertain	0.961	0.178	0.000											-10.482	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	1.63	Ambiguous	0.3	0.95	Ambiguous	1.29	Ambiguous	1.12	Destabilizing	0.279	Likely Benign	-5.97	Deleterious	0.998	Probably Damaging	0.987	Probably Damaging	3.93	Benign	0.22	Tolerated			0.1664	0.2883		2	0	1.0	-34.02
c.140G>A	R47Q 2D AIThe SynGAP1 missense variant R47Q is listed in ClinVar (ID 436920.0) as Benign and is present in gnomAD (6‑33423549‑G‑A). 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, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta results are unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Benign, and no Foldetta data to influence the conclusion. Overall, the majority of evidence points to a benign impact, consistent with the ClinVar classification; there is no contradiction with the reported ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.318242	Structured	0.436559	Uncertain	0.520	0.719	0.125					Likely Benign		1	6-33423549-G-A	4	2.48e-6	-4.989	Likely Benign	0.347	Ambiguous	Likely Benign										0.096	Likely Benign	-0.57	Neutral	0.829	Possibly Damaging	0.614	Possibly Damaging	4.12	Benign	0.00	Affected	4.32	1	0.3326	0.2591		1	1	1.0	-28.06																10.1016/j.ajhg.2020.11.011
c.1424G>A	R475Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R475Q is listed in ClinVar with an uncertain significance and is present in gnomAD (variant ID 6-33438456‑G‑A). Prediction tools that indicate a benign effect include AlphaMissense‑Optimized, Foldetta, and Rosetta. Those that predict a pathogenic effect comprise SGM Consensus, SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Default; FoldX and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points toward 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	0.175930	Structured	0.382696	Uncertain	0.852	0.261	0.000					Uncertain		2	6-33438456-G-A	5	3.10e-6	-12.087	Likely Pathogenic	0.721	Likely Pathogenic	Likely Benign	0.71	Ambiguous	0.1	0.12	Likely Benign	0.42	Likely Benign	0.82	Ambiguous	0.632	Likely Pathogenic	-3.65	Deleterious	1.000	Probably Damaging	0.991	Probably Damaging	-1.32	Pathogenic	0.01	Affected	3.39	28	0.2190	0.1926		1	1	1.0	-28.06	253.6	52.7	0.0	0.0	-0.8	0.0	X	X		X				Potentially Pathogenic	In the WT simulations, the guanidinium group of Arg475, located near the end of an α-helix (res. Ala461-Phe476), stacks with the phenyl ring of Phe476 and forms a salt bridge with Glu472. Additionally, Arg475 occasionally forms another salt bridge with the carboxylate group of Glu486 on the α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. Therefore, Arg475 potentially plays a key role in positioning the loop by interacting with Glu486, which is necessary for the positioning of the “arginine finger” (Arg485) and, ultimately, for RasGTPase activation. In the variant simulations, Asn475 forms a hydrogen bond with Arg479 on the proceeding α-α loop. The absence of Phe476/Arg475 stacking and the Arg475-Glu472 salt bridge weakens the integrity of the terminal end of the α-helix during the variant simulations. Lastly, the potential effect of the residue swap on the SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.1426T>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.